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Biomonitoring of industrial heavy metal pollution via enzymatic and metabolic responses in desert ants (Cataglyphis savignyi) and beetles (Tentyrum sp) as bioindicators.

The current work seeks to evaluate the effectiveness of Cataglyphis saviginyi and Tentyrum sp as indicators of pollution in the city's main industrial regions by analyzing their enzymatic activity and primary metabolites. Soil samples were collected at each site under investigation to analyze soil characteristics and heavy metal content. C. saviginyi and Tentyrum sp were collected across four consecutive seasons (2023-2024) to investigate enzymatic (GPT, GOT, ALP, ACP, LDH) and metabolic (lipid, protein, carbohydrate) biomarkers. The physicochemical properties of the soil differed substantially between the industrial areas and the control site. Soil heavy metal buildup was highest at industrial sites (1 and 4) compared to the control site, with the order being Zn > Cr > Cd > Cu. Heavy metal pollution indices were determined. Increased industrial activity from metal industries, ceramics, and chemical painting companies defines this area, as seen by the high Cdeg, mCd, PI, and PLI values derived for industrial sites 1 and 4. While C. saviginyi and Tentyrum sp deconcentrated and released Cr, Cd, and Zn into the soil via the biological accumulation factor (BAF), Cu acted as a macro-concentrator. Compared with the control site, industrial environments were shown to increase levels of GPT, GOT, LDH, ACP, protein, and carbohydrates in C. saviginyi. However, lipid and ALP activity was suppressed. at industrial sites, Tentyrum sp carbohydrate content was higher than at control sites, but GPT, GOT, ALP, ACP, LDH, protein, and lipid activities were all suppressed. Consequently, enzymatic and metabolic biomarkers proved to be sensitive indicators for assessing industrial heavy metal pollution in desert ecosystems.

Animals

Comparative analysis of DDR-related genes and microRNA expression during rice germination: Implications for salinity susceptibility screening.

Soil salinity poses a significant threat to the agri-food sector and particularly to rice cultivation. High salinity during germination induces overproduction of reactive oxygen species (ROS) that cause lesions in the DNA resulting in reduced vigor. MicroRNAs (miRNAs) are known to modulate stress response in plants, however, studies focusing on its relation with the expression of the DNA damage response (DDR)-related genes are not thoroughly explored. In this regard, the aim of this work was to investigate the link between the expression of miRNAs and putative targeted DDR-related genes in response to salinity stress during germination. Eight varieties representative of indica and japonica rice subspecies were categorized into clusters through a principal component analysis (PCA) based on their germination performance and stress tolerance index under varying concentrations of NaCl. Subsequently, the expression patterns of six miRNAs and their putative targeted DDR genes were measured in two contrastive cultivars through quantitative real-time PCR (qRT-PCR) while correlations were examined through Pearson's analysis. Results showed distinct expression profiles between halotolerant and sensitive cultivars. Two miRNAs were further investigated in mature dry seeds of all the cultivars to verify their earliest, seed-specific discriminative potential. The distinct miR414 expression pattern may represent a potential biomarker for identifying salinity-susceptible cultivars during early-stage breeding screening.

Oryza

Muscle mechanical and architectural adaptations in response to different endurance training modalities in older adults.

INTRODUCTION: This study examined the effects of various cycling endurance training modalities, matched for total workload, on muscle mechanical and architectural characteristics in older adults. METHODS: Fifty healthy participants (25 females, 59-79&#xa0;yrs) were randomly assigned to five age and sex matched groups: one control and four workload-matched training groups (moderate-intensity continuous, heavy-intensity continuous, high-intensity interval, and heavy-intensity continuous in eccentric cycling). Training consisted of three weekly sessions over 8&#xa0;weeks, with evaluations conducted at the beginning and end of the intervention with maximal voluntary isometric contractions at five different knee angles (90, 75, 60, 45, 30&#xb0;) and maximal concentric and eccentric isokinetic contractions at five different knee angular velocities (45, 90, 150, 210, 250&#xb0;/s). Maximum voluntary isometric torque (Tmax) and optimal knee angle (KAopt) were obtained from the isometric contractions; eccentric torque (Tecc) and maximum concentric knee angular velocity (Vmax) were obtained from the isokinetic contractions. The muscle architecture of vastus lateralis (VL) at rest (muscle thickness, pennation angle, and fascicle length) was investigated as well. RESULTS: No statistical differences were detected between groups or time points in VL architecture, in KAopt and in Vmax. A main effect of time was observed for Tmax (p&#xa0;<&#xa0;0.001, &#x3b7;2p&#xa0;=&#xa0;0.458) and Tecc (p&#xa0;=&#xa0;0.002, &#x3b7;2p&#xa0;=&#xa0;0.191) in all the investigated training groups. The within-group comparisons indicate significant increases in Tmax in the training groups, but not in the control group. CONCLUSIONS: Commonly applied endurance exercises improve muscle mechanical capacity (Tmax and Tecc) in older adults, with no structural (architectural) muscle remodelling, when matched for workload.

Humans

Lower-limb electromyographic responses across four recumbent cycling configurations in healthy young men.

Recumbent cycling provides an adjustable configuration in which backrest angle and crank-axis height can alter lower-limb loading. Backrest angle changes the orientation of the active musculature relative to gravity, whereas crank-axis height modifies the foot-pedal interface and the ankle lever arm. Whether such positioning is associated with differences in lower-limb electromyographic (EMG) activation across both factors together has not been examined. Using a randomized crossover design, fifty-nine healthy young men cycled at 100&#xa0;W and 50&#xa0;rpm under four conditions combining two backrest angles (30&#xb0;, 75&#xb0;) and two crank-axis heights (Rh, high, 77&#xa0;cm; Rl, low, 45&#xa0;cm). Surface EMG from the rectus femoris (RF), biceps femoris (BF), and gastrocnemius medialis (GAS) was analyzed for root mean square (RMS) amplitude, absolute onset sequence, and relative recruitment timing (%Sequence, derived using Telescan software and referenced to RF). RMS amplitude did not differ across conditions for any muscle (all p&#xa0;&#x2265;&#xa0;0.356), and absolute onset sequence showed no condition effect (all p&#xa0;&#x2265;&#xa0;0.197). For GAS %Sequence, the Greenhouse-Geisser-corrected omnibus test was significant (F(1.32, 76.56)&#xa0;=&#xa0;28.45, p&#xa0;<&#xa0;0.001), driven by a within-30&#xb0; contrast in which %Sequence was lower under Rl than Rh (paired t(58)&#xa0;=&#xa0;10.39, Holm-adjusted p&#xa0;<&#xa0;0.0001; mean difference 22.0 percentage points, 95&#xa0;% CI [17.8, 26.3]; dz&#xa0;=&#xa0;1.35). Because %Sequence is referenced to RF, this exploratory shift should be interpreted cautiously. Lower-limb activation may be constrained by the closed-chain nature of pedaling, whereas distal recruitment timing may be sensitive to crank-axis height and the foot-pedal interface.

Humans

First evaluation of a novel recombinant eCG molecule in ewes reveals a discrepancy between ovulatory response and pregnancy outcome.

This study evaluated the reproductive performance and clinical safety of a novel recombinant eCG (r-eCG) in ewes. Two weeks prior to study onset (Day 0: intravaginal progesterone device insertion), 45 ewes were randomly assigned to negative control (NC; no eCG; n&#x202f;=&#x202f;10), positive control (PC; 400IU commercial non-recombinant eCG; n&#x202f;=&#x202f;20), or treatment group (T; 400IU r-eCG; n&#x202f;=&#x202f;15). Ewes were inseminated with fresh-diluted semen (200&#x202f;&#xd7;&#x202f;106 sperm). Ultrasonography assessed follicle count/diameter (days 11, 13), ovulation (day 13), corpus luteum (CL) number/characteristics (day 20), and pregnancy (day 44). Serum progesterone was measured on day 20; Group T underwent clinical/hematological evaluations (days 0, 20, and 44). Estrus signs were more frequent (P&#x202f;<&#x202f;0.01) in T (100%) than NC (50%), while PC (85%) did not differ. Ovulation rates were similar between T (93%) and PC (95%), but higher than NC (50%; P&#x202f;<&#x202f;0.05). On day 13, largest follicle diameter did not differ (P&#x202f;>&#x202f;0.05) among groups; however, fewer follicles > 2&#x202f;mm occurred in PC than NC and T (P&#x202f;<&#x202f;0.05). CL number was higher in T than PC (2.0&#x202f;&#xb1;&#x202f;0.3 vs. 1.0&#x202f;&#xb1;&#x202f;0.0, P&#x202f;<&#x202f;0.01), while NC did not differ (1.0&#x202f;&#xb1;&#x202f;0.25). Conversely, pregnancy rate was higher (P&#x202f;<&#x202f;0.05) in PC (70%) than T (28.6%) and NC (20%). Among ovulated ewes, progesterone concentration and progesterone/CL ratio did not differ among groups (P&#x202f;=&#x202f;0.92 and P&#x202f;=&#x202f;0.08, respectively). No relevant r-eCG-related clinical or hematological alterations occurred. In conclusion, 400IU r-eCG effectively induces estrus and ovulation without adverse effects; however, the discrepancy between ovulatory response and pregnancy rate underscores the need for further study refinement to improve fertility.

Animals

Ribosomal protein S3: a critical regulator of human disease mechanisms.

Ribosomal protein S3 (RPS3) is an essential structural component of the 40S ribosomal subunit, yet growing evidence highlights crucial extraribosomal roles in genome maintenance, cell-cycle control, and immune signaling. Dysregulation of RPS3 contributes to diverse human disorders, including cancer, inflammatory diseases, neurodegeneration, and resistance to antimicrobial and anticancer therapies. As a cofactor of NF-&#x3ba;B and a participant in DNA damage responses, RPS3 occupies a node that integrates stress signaling with transcriptional reprogramming, enabling both protective and pathological outcomes. The present review critically evaluates mechanistic insights into RPS3 biology, emphasizing recent findings that delineate its context-dependent effects, discrepancies across models, and remaining gaps that restrict translational applications. Understanding these complexities is essential to assess RPS3's potential as a biomarker and therapeutic target.

Humans

Enhancement flavor quality in Zhao'an Baxian oolong tea through enhanced turning-over process.

A systematical investigation on the effects of turning-over intensity on the flavor formation of Zhao'an Baxian oolong tea (ZBT) was performed, through a comparative analysis of heavy turning-over (HT) and light turning-over (LT) treatments in this study. The tea samples were subjected to proteomic and metabolomic analyses, combined with quantitative descriptive analysis (QDA) and electronic sensory (E-tongue/E-nose) evaluation. The results demonstrate that HT significantly reduced the content of bitter and astringent compounds, such as catechins and flavonol glycosides, while promoting the accumulation of umami-related amino acids. Concurrently, HT enhanced the biosynthesis of key floral and fruity volatiles, such as &#x3b2;-ocimene, geraniol, benzaldehyde, jasmone by activating stress-responsive metabolic pathways. These coordinated biochemical changes, driven by enzyme-catalyzed reactions in response to prolonged mechanical wounding and environmental stress, collectively improved the overall sensory profile of ZBT. These findings provide a mechanistic foundation for improving ZBT production, with clear implications for quality control and flavor-oriented product development.

Tea

Self-healing materials for food packaging: Design principles, activation mechanisms and implications for food safety.

Self-healing materials (SHMs), originally developed to restore mechanical integrity, have recently attracted growing interest in food packaging. By autonomously repairing physical damage, SHMs help preserve packaging integrity, barrier performance, food safety, and shelf-life during storage and transportation. This review summarizes recent advances in the design principles, activation mechanisms, material systems and food packaging applications of SHMs. Key healing strategies, including microencapsulation, dynamic covalent bond exchange, reversible non-covalent interactions and responsiveness to external stimuli such as temperature, pH, and humidity, are discussed. Representative material systems, including biopolymer-based films, hydrogels, nanocomposites, and stimuli-responsive polymers are evaluated with respect to their relevance to packaging animal-derived foods, fruits, and vegetables. Performance evaluation methods, sustainability implications, and food-contact safety concerns are addressed. Despite promising healing efficiency and mechanical resilience, challenges remain regarding production cost, food-grade safety, migration risks, trigger compatibility and stability under fluctuating environmental conditions. Future research should focus on scalable manufacturing, standardized evaluation protocols, repeated damage-healing safety assessment, regulatory compliance, and integration with intelligent packaging technologies.

Food Packaging

Early hepatic protein responses to dietary restriction-refeeding in Japanese quail: A proteomic investigation.

Feed intake and refeeding after nutrient scarcity induce rapid metabolic adaptations in the poultry liver; however, hepatic proteomic recovery pathways in the early hours post-refeeding remain poorly defined. This study aimed to characterize early liver protein signatures in Japanese quail (Coturnix japonica) recovering from nutritional stress under two refeeding conditions. Eighteen 12-week-old male quails (245.20&#xa0;&#xb1;&#xa0;0.213&#xa0;g) were assigned to three groups (n&#xa0;=&#xa0;6): control fed ad libitum (12.13&#xa0;MJ/kg), 24&#xa0;h feed deprivation followed by 6&#xa0;h refeeding, and 24&#xa0;h low metabolizable energy (6.30&#xa0;MJ/kg) diet followed by 6&#xa0;h refeeding. In total, 854 proteins were identified, of which 515 met the filtering criteria. The low metabolizable energy refeeding showed higher abundance of proteins linked to ATP binding and carbohydrate/carboxylic acid metabolism, alongside detoxification-related proteins, while suppressing translation/RNA-binding machinery and antioxidant pathways. Feed-deprived refeeding enriched in oxidative phosphorylation and mitochondrial complex I assembly with reduced cytoplasmic translation, NMD-related components, and sulfur compound metabolism. A direct comparison indicated divergent recovery strategies: low metabolizable energy refeeding mainly reflected oxidoreductase activity and translation initiation, whereas feed-deprived refeeding potentially enriched mitochondrial ATP production and glutathione-based defenses. Our analysis indicate that 6&#xa0;h of refeeding initiates an early, incomplete recovery toward hepatic homeostasis, with the severity of prior nutritional restriction dictating distinct liver metabolic priorities. Collectively, these findings might provide a preliminary understanding of the hepatic mechanisms involved in recovery from nutrient deprivation and may help in the development of feeding strategies for managing metabolic recovery in poultry. However, these findings should be considered hypothesis-generating pending further validation.

Animals

Phase-resolved functional lung MRI detects single-dose and sustained bronchodilator responses in COPD in a randomized crossover trial.

OBJECTIVES: To evaluate the effects of tiotropium/olodaterol (T/O) on phase-resolved functional lung (PREFUL) MRI parameters in hyperinflated chronic obstructive pulmonary disease (COPD) patients and examine correlations with conventional cardiopulmonary and hyperpolarized 129Xe MRI measures. MATERIALS AND METHODS: Retrospective subanalysis of a prospective, randomized, placebo-controlled, crossover trial with open-label extension. Thirty-two patients with moderate-to-severe COPD (61.5&#x2009;&#xb1;&#x2009;7.7 years; 17 men); 30 completed the MRI extension at 1.5&#x2009;T. PREFUL analysis yielded regional ventilation (RVent), flow-volume loop correlation metric (FVL-CM), normalized perfusion (QN), ventilation defect percentage (VDP), perfusion defect percentage (QDP), V/Q match metrics (VQM), and pulmonary pulse wave velocity (PWV; post-hoc parameter). Linear mixed-effects models tested treatment effects; correlations were evaluated with Spearman's rank and bootstrap 95% confidence intervals (95% CIs). RESULTS: PREFUL parameters improved after T/O single dose (SD) versus placebo, including improvements in FVL-CM by 4.1 percentage points (pp; 95% CI: 1.0 to 7.3 pp) and QN by 0.4 pp (95% CI: 0.2 to 0.6 pp) and reductions in VDP and QDP, with parallel gains in VQM(Non-Defect) (p&#x2009;<&#x2009;0.05). PWV decreased after multiple doses (-0.87&#x2009;m/s, 95% CI: -1.26 to -0.48&#x2009;m/s). PREFUL MRI baseline values showed significant correlations with pulmonary function tests, cardiac, dynamic contrast-enhanced and 129Xe MRI. SD treatment-induced absolute changes in VDP(FVL-CM) correlated with reductions in residual volume (&#x3c1;&#x2009;=&#x2009;0.41, 95% CI: 0.02 to 0.64). Further correlations were observed between PREFUL MRI and &#xb9;&#xb2;&#x2079;Xe-derived VDP, apparent diffusion coefficient, and compartment ratios. CONCLUSION: PREFUL MRI sensitively captured immediate SD T/O-induced improvements in V/Q parameters and dose-dependent PWV responses after sustained bronchodilation. KEY POINTS: Question Can phase-resolved functional lung (PREFUL) MRI sensitively capture immediate single-dose and sustain multi-dose effects of tiotropium/olodaterol on ventilation-perfusion and vascular function in COPD patients? Findings Tiotropium/olodaterol improved PREFUL MRI-derived ventilation, perfusion, and V/Q matching parameters after a single dose, with sustained pulmonary vascular improvements after repeated dosing. Clinical relevance PREFUL MRI detected immediate and sustained functional improvements after tiotropium/olodaterol and showed significant correlations with cardiopulmonary tests and hyperpolarized &#xb9;&#xb2;&#x2079;Xe MRI, supporting its role as a sensitive, radiation-free tool for monitoring COPD treatment response.

Humans

Association between fruit and vegetable intake and risk of depression: A systematic review and meta-analysis of prospective cohort studies.

Depression is a leading cause of global disability, and identifying modifiable lifestyle factors is a public health priority. We conducted a systematic review and dose-response meta-analysis of prospective cohort studies examining the association between fruit and vegetable intake and incident depression. PubMed, Web of Science, Scopus, Embase, and Google Scholar were searched through November 2025. Data on study characteristics, dietary assessment, outcomes, effect estimates, and covariates were independently extracted by two reviewers. Random-effects models were used to calculate pooled relative risks (RRs), and linear and non-linear dose-response relationships were assessed. Heterogeneity was evaluated using I2, and evidence certainty was rated with GRADE. Thirteen cohorts with 385,449 participants and 26,592 depression cases were included. Highest versus lowest combined fruit and vegetable intake was associated with a 37% lower risk of depression (RR: 0.63; 95% CI: 0.50, 0.80). Each 200&#xa0;g/day increase corresponded to a 16% risk reduction (RR: 0.84; 95% CI: 0.74-0.94). Separate analyses showed that fruit and vegetable intake reduced depression risk by 16% and 12%, respectively, with a non-linear dose-response for vegetables. These findings indicate that higher consumption of fruits and vegetables is associated with lower depression risk, supporting dietary strategies as a potential approach for mental health prevention. However, given the observational nature of the included studies, these results should be interpreted with caution, as residual confounding may partially account for the observed associations. Registration: This study was registered at PROSPERO (CRD420261279998).

Humans

Health risk assessment of inorganic arsenic: an umbrella review.

Inorganic arsenic (iAs) is a toxic environmental pollutant linked to serious health risks, prompting global regulatory efforts. This study identifies major health conditions associated with iAs exposure using text network analysis, and assesses health risk assessments through an umbrella review and dose-response analysis. It synthesizes previous systematic reviews to offer a broader perspective on iAs-related health effects. An optimized text network analysis-based search strategy was applied across multiple databases to identify relevant systematic reviews. An umbrella review framework was employed to synthesize and reinterpret findings across systematic reviews. The methodological quality of included systematic reviews was assessed using the A MeaSurement Tool to Assess systematic Reviews 2 tool. Extracted data on study characteristics, exposure levels, and risk estimates were analyzed to evaluate the dose-response relationship between iAs exposure and health outcomes. From 922 systematic reviews, 36 were included and categorized into 10 health condition groups. For example, seven SRs found a significant dose-response relationship between iAs and bladder cancer, with one systematic review reporting relative risks of 2.70, 4.20, and 5.80 at 10, 50, and 150&#x202f;&#xb5;g/L, respectively. Individual study analysis further showed that each 10&#x202f;&#xb5;g/L increase in iAs raised bladder cancer risk by 3.11&#x202f;% (p=0.003). iAs exposure is associated with hypertension, diabetes, cardiovascular disease, and adverse fetal outcomes. Dose-dependent increases in bladder cancer, lung cancer, and hypertension risks were observed. These findings support more precise health risk assessments and regulatory strategies.

Humans

Transcriptomic insights into thermal stress reveal physiological trade-off between thermal stress adaptation and reproductive investment in Spodoptera litura.

Spodoptera litura, a highly polyphagous lepidopteran pest, poses a major threat to agricultural productivity due to its remarkable adaptability to diverse environmental conditions. Although heat stress is known to trigger transcriptional reprogramming in insects, the molecular mechanisms underlying thermal stress responses in S. litura remain poorly understood. In the present study, fourth-instar larvae were exposed to acute heat stress (44&#xa0;&#xb0;C) and compared with control conditions (27&#xa0;&#xb1;&#xa0;1&#xa0;&#xb0;C) to investigate heat-induced transcriptional alterations affecting physiology and reproduction. High-quality RNA-Seq data achieved more than 80% mapping efficiency, with a total of 15,782 transcripts were identified. Transcriptome analysis of S. litura larvae showed 323 differentially expressed genes (DEGs), of which 262 genes were significantly upregulated and 61 were downregulated in heat-stressed larvae compared to the control group. The DEGs were associated with stress response, reproduction, signalling, proteostasis, detoxification, oxidative stress, metabolism, development, and chromatin regulation. Heat shock proteins genes, including HSP70, HSP90, and HSP27, together with co-chaperones such as TRET-1, STIP1, and Starvin, were strongly upregulated, indicating enhanced cellular protection against protein damage and oxidative stress under heat stress. Conversely, key reproductive and cell cycle-related genes, including BARR, CAPD2, FEO, CDK2 and MORULA, were significantly downregulated, suggesting reproductive impairment and developmental arrest. RT-qPCR validation corroborated the RNA-Seq findings, demonstrating a heat-induced physiological trade-off that prioritizes survival over reproduction. Consistent with these molecular responses, heat-stressed insects exhibited marked reproductive impairment, including significant reductions in gonadosomatic index, eupyrene sperm bundle count, mating frequency, mating success, female calling behaviour, copulation duration, fecundity, and egg fertility. Collectively, these findings provide comprehensive insights into the molecular basis of thermal adaptation in S. litura and demonstrate that acute heat stress compromises reproductive fitness while activating conserved stress-response pathways that promote short-term survival.

Animals

Biologic-biologic and biologic-JAK inhibitor combination therapy in refractory systemic autoinflammatory diseases.

OBJECTIVES: Systemic autoinflammatory diseases (SAIDs) arise from genetic defects in innate immunity, leading to dysregulated activation of inflammatory pathways, including interleukin (IL)-1, IL-6, TNF, and JAK/STAT. Clinical manifestations range from recurrent fever to severe complications such as encephalitis and AA amyloidosis. Management aims to control inflammation using immunosuppressive agents and targeted monotherapies (biologics or JAK inhibitors). Advanced combination therapy (ACT), defined as the use of biologics and/or JAK inhibitors in combination, has emerged as a strategy for refractory disease. METHODS: In this observational retrospective longitudinal cohort study, patients with SAIDs treated with ACT were included. Demographic, clinical, treatment, and safety data were collected. Treatment response was assessed using a composite outcome incorporating corticosteroid dose, C-reactive protein (CRP), and clinical improvement and categorized as non-response, partial response, or complete response. RESULTS: Thirty-eight patients (median age 30 years [range 4-76]) were included. The most common indications for ACT were pyogenic arthritis, pyoderma gangrenosum and acne (PAPA), mevalonate kinase deficiency (MKD), and undifferentiated SAIDs. Most patients had disease-related complications and were dependent on glucocorticoids and/or opioids to control inflammation and pain, respectively. Following multiple ACT trials, complete response was observed in 21 patients (55.3%), partial response in 12 (31.6%), and no response in 5 (13.1%). Overall, 65 ACT regimens were administered, most commonly combining IL-1 and TNF inhibitors. Thirty-nine regimens were discontinued because of lack of efficacy, secondary loss of response, or adverse events. At the final follow-up, 26 patients (68%) remained on ACT, with a median treatment duration of 60 months (range, 11-186). CONCLUSIONS: ACT offers significant clinical benefits for patients with difficult-to-treat SAIDs, though challenges such as secondary loss of efficacy and infection risks remain.

Humans

Transient acoustic stimulation induces time-dependent synaptic remodeling and enhancement of auditory nerve output after threshold recovery.

BACKGROUND: Acoustic stress can alter cochlear function even in the absence of permanent threshold elevation; however, synaptic consequences of transient acoustic stimulation remain incompletely understood. OBJECTIVE: This study aimed to investigate whether transient acoustic stimulation induces changes in the auditory nerve output and cochlear ribbon synapse morphology following hearing threshold recovery. METHODS: Young adult CBA/CaJ mice were exposed to band-limited acoustic stimulation (45-2,000&#xa0;Hz, 95&#xa0;dB SPL, 2&#xa0;h). Auditory brainstem responses (ABRs), hair cell and spiral ganglion neuron survival, and synaptic morphology were evaluated before exposure and up to 2&#xa0;weeks post-exposure. RESULTS: ABR thresholds were transiently elevated immediately after exposure but largely recovered by 1&#xa0;day post-exposure. In contrast, ABR wave I amplitudes significantly increased after threshold recovery across multiple test frequencies. Ribbon-associated puncta in both inner and outer hair cell regions exhibited biphasic temporal changes, with an initial decrease immediately after exposure followed by an increase at 1&#xa0;day post-exposure. The ribbon-associated punctal area also increased after exposure and remained elevated at later post-exposure time points. No significant loss of hair cells or spiral ganglion neurons was observed. Exploratory genomic analysis suggested enrichment of pathways related to metabolic defense and cellular stress responses. CONCLUSIONS: Transient acoustic stimulation induces time-dependent synaptic remodeling and enhancement of peripheral auditory nerve output without overt cellular degeneration. These findings support a model in which early cochlear responses to acoustic perturbation include adaptive synaptic plasticity and gain regulation, extending current concepts of noise-induced cochlear change beyond irreversible synaptic loss.

Animals

Multi-omics integrative analysis provides insight into potential molecular responses to sustained high water flow in common carp (Cyprinus carpio) cultured in recirculating aquaculture.

To investigate the potential molecular responses by which water flow intensity affects the growth of common carp (Cyprinus carpio) in a recirculating aquaculture system (RAS), a control group (CG, actual water velocity 0.3&#xa0;cm/s) and three sustained flow treatment groups were established, including a low-flow group (LF, 1 body length per second, bl/s), a medium-flow group (MF, 2 bl/s), and a high-flow group (HF, 3 bl/s). After 12&#xa0;weeks of culture in the RAS, growth performance was compared among groups under different flow intensities. The best-performing group and the control group were then selected for the determination of intestinal digestive enzyme activities, as well as transcriptomic and whole-genome bisulfite sequencing analyses of muscle tissue. The results showed that the specific growth rate and feed intake of the HF group were significantly higher than those of the other groups (P&#xa0;<&#xa0;0.05), whereas no significant difference in feed conversion ratio was observed among groups. Compared with the CG group, lipase activity was significantly higher in the HF group (P&#xa0;<&#xa0;0.05), while &#x3b1;-amylase and trypsin activities showed increasing trends without significant differences. RNA-seq identified a total of 273 differentially expressed genes, including 72 upregulated genes and 201 downregulated genes in the HF group relative to the CG group. These genes were mainly enriched in glycolysis, pyruvate metabolism, ATP metabolism, the pentose phosphate pathway, the insulin signaling pathway, the PPAR signaling pathway, and the adipocytokine signaling pathway, indicating that sustained high water flow induced a muscle transcriptional response characterized by remodeling of energy metabolism and substrate utilization. Whole-genome bisulfite sequencing analysis showed that DNA methylation in common carp muscle occurred predominantly in the CpG context. Differentially methylated regions between the HF and CG groups were mainly distributed in transcription-related regulatory regions, including promoters, CpG islands, and CpG island shores. In promoter regions, the number of hypermethylated regions in the HF group relative to the CG group was markedly higher than that of hypomethylated regions. Integrated analysis further identified two candidate genes showing both promoter differential methylation and differential expression, namely LOC109094644 and bcorl1, suggesting that adaptation to high water flow may involve IGF-related growth regulation and remodeling of upstream transcriptional programs. The qPCR results were consistent with the transcriptomic data. Taken together, within the tested range, a sustained water flow of 3 bl/s was more conducive to the growth of common carp in the RAS, which may be associated with enhanced lipid digestion and utilization, remodeling of the muscle energy metabolic network, changes in promoter methylation, and the coordinated regulation of key candidate genes. This study provides a theoretical basis for clarifying the exercise adaptation mechanism of common carp in recirculating aquaculture and for optimizing flow velocity parameters.

Animals

Cloning of two Hsp70 genes and association analysis between SNP haplotypes and high temperature tolerance trait in red swamp crayfish (Procambarus clarkii).

Aquaculture is suffering the challenge from high temperature climate. Two Hsp70 genes, PcHsp70-1 and PcHsp70-2, as key genes involved in the high temperature tolerance of red swamp crayfish (Procambarus clarkii) were identified and cloned in this study. Their molecular features and expression patterns were characterized, revealing the distinct tissue-specific upregulation expression under high temperature stress (33&#xa0;&#xb0;C). Two SNPs, PcHsp70-1 (SNP258) and PcHsp70-2 (SNP555) were examined to associate with high temperature tolerance in three populations (n&#xa0;=&#xa0;675). The genotypes of PcHsp70-1-SNP258 (GA) and PcHsp70-2-SNP555 (TT) were significantly associated with stronger high temperature tolerance. Notably, individuals carrying the haplotype of Hap I (GG&#xa0;+&#xa0;TT) showed a survival rate exceeding 70% under high temperature stress, whereas, the Hap VIII (AA + CT) showed it at 5.2%. RNA interference of PcHsp70-1 resulted in a significant decrease expression of the gene GSH-Px and its encoding protein (glutathione peroxidase) activity, and damage in intestinal tissue under high temperature stress. The transcriptome result revealed that PcHsp70-1 participates in regulation of the pathways related to cytoskeletal construction, immune response, apoptosis, and antioxidant defense. These findings indicate that PcHsp70 genes are crucial for the cellular stress response under high temperature stress. The developed Kompetitive Allele Specific PCR (KASP) markers provide valuable tools for the marker-assisted selection of high temperature tolerant crayfish varieties, supporting the sustainable development of aquaculture under the challenge of global warming.

Animals

Chemoradiotherapy versus short-course radiotherapy for response-adapted organ preservation in early-stage and intermediate-stage rectal cancer (STAR-TREC): 12-month results of an international, multicentre, open-label, parallel-group, randomised, phase 2/3 trial.

BACKGROUND: Total mesorectal excision (TME) is the standard treatment for most early-stage and intermediate-stage rectal cancer but can cause substantial perioperative morbidity, functional impairment, and reduced quality of life. We assessed whether long-course chemoradiotherapy (LCCRT) or short-course radiotherapy (SCRT) could increase organ preservation and reduce surgery, toxicity, and quality-of-life harms without compromising oncological outcomes. METHODS: STAR-TREC is an international, multicentre, open-label, parallel-group, randomised, phase 2/3 trial in five European countries. Eligible patients were aged 16 years or older in the UK or aged 18 years or older elsewhere, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and rectal adenocarcinoma (&#x2264;40 mm staged as mrT1-T3bN0). In phase 2, participants were randomly assigned (1:1:1) to LCCRT-based organ preservation (LCCRT-OP; 50 Gy in 25 fractions plus oral capecitabine 825 mg/m2 twice daily), SCRT-based organ preservation (SCRT-OP; 25 Gy in five fractions), or primary TME. Phase 2 assessed feasibility, with recruitment at months 12 and 24 as the primary endpoint and feasibility thresholds of four or more and six or more randomisations per month, respectively. Phase 3 adopted a partially randomised patient-preference design, allowing participants to choose either organ preservation or TME. Participants that chose organ preservation were randomly assigned (1:1) to receive LCCRT-OP or SCRT-OP using centralised, computer-generated assignment, with stratification by country and MRI T category (&#x2264;T3a vs T3b) using minimisation. The phase 3 primary endpoint was organ-preservation 30 months after treatment initiation, defined as absence of TME, stoma, or local recurrence, which was assessed in the modified intention-to-treat population, which included participants in phase 2 and phase 3. After a planned interim analysis of unmasked phase 2 data, the trial steering committee and independent data monitoring committee recommended reporting a 12-month, modified intention-to-treat analysis of implementation outcomes for participants recruited before Aug 8, 2023. This study is registered with ISRCTN (14240288) and is closed. FINDINGS: Between June 14, 2017, and April 8, 2024, 503 participants were enrolled at 37 sites. Phase 2 enrolled 120 participants, with recruitment rates of three and six participants per month at months 12 and 24, respectively. Overall, 12-month TME-free survival was 60% (47 of 78 participants). After phase 3 recruitment ended, interim analysis of unmasked phase 2 data showed an early TME-free survival benefit with LCCRT versus SCRT (12-month median TME-free survival not reached [95% CI not reached-not reached] vs 7&#xb7;6 months [95% CI 6&#xb7;4-not reached]; hazard ratio [HR] 3&#xb7;7 [95% CI 1&#xb7;7-8&#xb7;0]; posterior probability of superiority >99&#xb7;5%). The trial steering committee and independent data monitoring committee therefore recommended expanded analysis of 426 participants recruited before Aug 8, 2023: 120 from phase 2 and 306 from phase 3. 17 participants withdrew before treatment, leaving 409 in the modified intention-to-treat population: 163 allocated to LCCRT, 168 to SCRT, and 78 to primary TME. 116 (28%) participants were female and 293 (72%) were male. Among participants who opted for organ preservation, 12-month TME-free survival was 78&#xb7;5% (95% CI 72&#xb7;4-85&#xb7;1) with LCCRT and 60&#xb7;6% (53&#xb7;6-68&#xb7;4) with SCRT (HR 1&#xb7;90 [95% CI 1&#xb7;29-2&#xb7;81]). The most common grade 3-4 serious adverse events were gastrointestinal disorders (four [2%] with LCCRT vs six [4%] with SCRT vs six [8%] with TME) and procedural complications (three [2%] with LCCRT vs five [3%] with SCRT vs five [6%] with TME). One participant allocated to primary TME died after an anastomotic leak. INTERPRETATION: These early results support a response-adapted organ-preservation approach, with LCCRT appearing more effective than SCRT at 12 months. Organ-preservation might also reduce treatment-related toxicity compared with primary TME. Longer follow-up is needed for the prespecified 30-month endpoint and definitive functional and oncological outcomes. FUNDING: Cancer Research UK, Stand Up to Cancer, Dutch Cancer Society, Danish Cancer Society, Kom Op Tegen Kanker, Cancerfonden, ALF Region Stockholm, RCC Region Stockholm.

Humans