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Efficacy and Safety of a Single-Pill Triple Combination of Valsartan, Amlodipine, and Chlorthalidone in Patients With Essential Hypertension Inadequately Controlled on Dual Therapy With Valsartan and Amlodipine: A Randomized, Double-Blind, Multicenter, Phase 3 Trial.

Many hypertensive patients require three or more antihypertensive agents to achieve target blood pressure. This randomized, double-blind, multicenter phase 3 trial conducted in South Korea evaluated the efficacy and safety of a single-pill triple combination therapy with valsartan (Val), amlodipine (Aml), and chlorthalidone (CTD) in patients whose blood pressure remained inadequately controlled on Val/Aml dual therapy. Patients uncontrolled after 4 weeks of Val/Aml 80/5&#xa0;mg were randomized 1:1 to either Val/Aml/CTD 80/5/12.5&#xa0;mg or Val/Aml 80/5&#xa0;mg using a double-dummy design. After 2 weeks, doses were escalated to Val/Aml/CTD 160/5/25&#xa0;mg or Val/Aml 160/5&#xa0;mg, respectively, for a total treatment duration of 6 weeks. The primary endpoint was the change in mean sitting systolic blood pressure (MSSBP) from baseline to week 8. Of 193 randomized patients, 178 completed the study. The least squares mean &#xb1; SE change in MSSBP was -19.70 &#xb1; 1.31&#xa0;mmHg in the Val/Aml/CTD group versus -8.71 &#xb1; 1.26&#xa0;mmHg in the control group, yielding a statistically significant between-group difference of -10.99 &#xb1; 1.81&#xa0;mmHg (95% CI, -14.56 to -7.41; p < 0.0001). No serious adverse events occurred in the Val/Aml/CTD group, compared with an incidence of 1.98% in the control group (p = 0.4985). Triple combination therapy with Val/Aml/CTD demonstrated superior blood pressure reduction and a favorable safety profile in patients with essential hypertension inadequately controlled on Val/Aml dual therapy, supporting its use as an effective treatment option in this population. Trial Registration: This trial was prospectively registered at ClinicalTrials.gov (identifier: NCT06416865).

Humans

Air Pollution and Heat Impacts on Respiratory Morbidity and Mortality Outcomes in Africa: A Systematic Review Towards a Meta-analysis.

PURPOSE OF THE REVIEW: This review synthesised evidence on associations between air pollution and respiratory morbidity in Africa. Following PRISMA guidelines, we systematically searched PubMed, ScienceDirect and Elicit for case-control studies published between 2015 and 2025. RECENT FINDINGS: Thirteen studies from ten African countries reported pollutant levels far exceeding WHO guidelines. Indoor PM&#x2082;.&#x2085; in biomass-using homes ranged from 96 to 177&#xa0;&#xb5;g/m&#xb3;, and ambient PM&#x2082;.&#x2085; reached 259&#xa0;&#xb5;g/m&#xb3;. Nitrogen oxides were consistently associated with reduced lung function in children, while household air pollution increased risks of under-five mortality and low birthweight. Associations with acute respiratory infections varied across settings. Vulnerability was greatest among young children, those with airway hyperresponsiveness, and households with poor ventilation. Only three studies included temperature, and none examined heat-respiratory interactions. Across African case-control studies, particulate matter and household air pollution remain consistently linked to adverse respiratory outcomes, highlighting urgent needs for cleaner fuels, improved ventilation, and stronger evidence on combined pollution and heat exposures.

Humans

Barefoot ambulation following partial foot amputation: A systematic review of biomechanical outcomes.

BACKGROUND: Partial foot amputation (PFA) is increasingly performed due to rising prevalence of diabetes and peripheral vascular disease. While PFA may preserve gait and reduce energy expenditure compared with transtibial amputation, biomechanical deficits are common. This review aimed to evaluate biomechanical outcomes during baref following PFA. METHODS: A systematic review was conducted. MEDLINE, Embase, CINAHL, SCOPUS and Web of Science databases were searched for studies reporting biomechanical outcomes in adults with PFA without prosthesis. Eligible outcomes included spatiotemporal metrics, joint kinematics and kinetics, plantar pressures, and ground reaction forces. FINDINGS: Twelve studies including a total of 101 participants met inclusion criteria. Across studies, PFA was associated with impaired barefoot gait. This included spatiotemporal changes, such as reduced walking speed and shorter step length, and kinetic changes, such as reduced ankle power. Elevated plantar pressures were commonly reported, particularly in the forefoot and midfoot, highlighting loading abnormalities in the residuum. Several studies also described proximal compensatory strategies at the knee and hip, suggesting that biomechanical consequences extend beyond the foot and ankle. However, the evidence base was limited by small sample sizes, inconsistent protocols, and substantial heterogeneity. INTERPRETATION: Barefoot walking is impaired after partial foot amputation and the degree of dysfunction may vary by amputation level. Abnormal loading and compensatory changes may extend beyond the foot and ankle to the knee and hip. Given the limited and methodologically heterogeneous evidence, larger prospective studies with standardised biomechanical outcomes are needed to clarify the effects of amputation level and aetiology. This standardisation is important to inform surgical planning, rehabilitation, and prosthetic device design.

Humans

[Effect of electroacupuncture combined with suspension exercise therapy on lower limb motor function in elderly patients with post-stroke spastic hemiplegia].

OBJECTIVE: To observe the efficacy of electroacupuncture (EA) combined with suspension exercise therapy in elderly patients with post-stroke spastic hemiplegia and its effect on lower limb motor function. METHODS: A total of 120 elderly patients with post-stroke spastic hemiplegia were enrolled. Using a 2&#xd7;2 factorial design, all the patients were assigned to a group A (conventional treatment), a group B (conventional treatment combined with suspension exercise therapy), a group C (conventional treatment combined with EA at Jiaji [EX-B2] and limb acupoints), and a group D(conventional treatment combined with suspension exercise therapy and EA at Jiaji [EX-B2] and limb acupoints), with 30 patients in each group. The main acupoints were bilateral Jiaji (EX-B2) points at the C2-C7, T2-T12, L1-L5, and S1 segments. The adjunct acupoints included Jianyu (LI15), Binao (LI14), Huantiao (GB30), Chengfu (BL36), etc. on the affected side.Continuous wave was applied at a frequency of 100 Hz with a current intensity of 1.5-3.0 mA, and needles were retained for 30 min, once daily for 4 weeks. Before treatment and after 2 and 4 weeks of treatment, the modified Ashworth scale (MAS),Fugl-Meyer assessment (FMA), Berg balance scale (BBS), and Barthel index scores were evaluated in the four groups. Root mean square (RMS) values of surface electromyography (sEMG) of the erector spinae and rectus abdominis muscles on the affected side, as well as balance function indexes, including the mean pressure symmetry index (SI), contact area SI, ellipse area, and displacement distances of the center of pressure in the anteroposterior (AP) and mediolateral (ML) directions, were measured. Clinical efficacy was also compared among the four groups. RESULTS: After 2 and 4 weeks of treatment, MAS scores in all groups were lower than those before treatment (P<0.05), whereas FMA, BBS, and Barthel index scores were higher than those before treatment (P<0.05). After 4 weeks of treatment, MAS scores were lower than those after 2 weeks of treatment (P<0.05), whereas FMA, BBS, and Barthel index scores were higher than those after 2 weeks of treatment (P<0.05) in the four groups. At both 2 and 4 weeks after treatment, group D had lower MAS scores (P<0.05) and higher FMA,BBS, and Barthel index scores (P<0.05) than the other three groups. After 2 and 4 weeks of treatment, RMS values of sEMG of the erector spinae and rectus abdominis muscles on the affected side at all tested angles were higher than those before treatment in all groups (P<0.05), and the values after 4 weeks of treatment were higher than those after 2 weeks of treatment(P<0.05). At both 2 and 4 weeks after treatment, all these indexes in the group D were higher than those in the other three groups (P<0.05). After 2 and 4 weeks of treatment, the mean pressure SI, contact area SI and ellipse area of each group were lower than those before treatment (P<0.05). After 4 weeks of treatment, the mean pressure SI, contact area SI and ellipse area of each group were lower than those after 2 weeks of treatment (P<0.05). After 2 and 4 weeks of treatment, the AP displacement distances of groups A, C and D were lower than those before treatment (P<0.05), and after 4 weeks of treatment, the AP displacement distances of groups A, C and D were lower than those after 2 weeks of treatment (P<0.05);after 2 weeks of treatment, there was no statistically significant difference in AP displacement distance in the group B compared with before treatment (P>0.05), and after 4 weeks of treatment, the AP displacement distance of group B was lower than that before treatment (P<0.05). After 2 weeks of treatment, there was no statistically significant difference in ML displacement distance in group A compared with before treatment (P>0.05); after 4 weeks of treatment, the ML displacement distance of group A was lower than that before treatment (P<0.05). After 2 and 4 weeks of treatment, there was no statistically significant difference in ML displacement distance in the group B compared with that before treatment (P>0.05).After 2 and 4 weeks of treatment, the ML displacement distances of groups C and D were lower than those before treatment(P<0.05), and after 4 weeks of treatment, the ML displacement distances of groups C and D were lower than those after 2 weeks of treatment (P<0.05). At both 2 and 4 weeks after treatment, mean pressure SI, contact area SI, ellipse area, and AP and ML displacement distances in the group D were lower than those in the other three groups (P<0.05). Factorial analysis of variance showed that EA had the strongest main effect on FMA score (F=6.243, P<0.05), suspension exercise therapy had the strongest main effect on BBS score (F=6.292, P<0.05), and the interaction effect was most significant for MAS score (F=5.941, P<0.05), indicating that the combined therapy produced a greater synergistic effect on reducing muscle tone than on the other outcome measures. The total effective rate in the group D was 93.3% (28/30), which was higher than those in the group A (53.3% [16/30]), group B (56.7% [17/30]), and group C (66.7% [20/30], P<0.05). CONCLUSION: EA combined with suspension exercise therapy could effectively promote the recovery of lower limb function in elderly patients with post-stroke spastic hemiplegia, improve motor and balance functions, and enhance activities of daily living.

Humans

Improved donor-site biomechanics and functional recovery with xenogeneic acellular dermal matrix after ALT flap harvest: A prospective randomized controlled study.

BACKGROUND: Donor-site management after anterolateral thigh (ALT) flap harvest is a significant yet underaddressed concern in reconstructive surgery for oral cancer. While xenogeneic acellular dermal matrix (Xeno-ADM) is common in soft-tissue repair, its efficacy for fascia lata reconstruction at the ALT donor site remains insufficiently characterized. This study aimed to assess the efficacy of xeno-ADM in fascia lata repair, focusing on compartment pressure, inflammatory and muscle injury biomarkers, and functional recovery. METHODS: In this prospective, randomized, single-blind trial, 200 patients undergoing ALT flap reconstruction were allocated to Xeno-ADM repair (n&#x202f;=&#x202f;100) or primary closure (n&#x202f;=&#x202f;100). Primary endpoints included compartment pressure, inflammatory markers in drainage fluid, serum muscle injury biomarkers, and functional outcomes. RESULTS: The xeno-ADM group showed significantly lower compartment pressures throughout postoperative days (POD) 1-5. Inflammatory markers in drainage fluid (CRP on POD 3 and 5) and serum muscle injury biomarkers (creatine kinase on POD 1 and 5) were significantly lower in xeno-ADM group. Functional outcomes were superior in the Xeno-ADM group, with faster gait recovery, lower pain scores at POD 7, and better lower-limb function at the 1- and 6-month follow-ups. Drainage duration did not differ between groups. Stratified analyses revealed that the benefits of xeno-ADM were more pronounced in patients with defect width >3&#x202f;cm or a body mass index &#x2265;24&#x202f;kg/m2. CONCLUSION: Xeno-ADM provides a safe and effective approach for fascia lata repair, reducing biomechanical and inflammatory burdens while enhancing functional recovery. These findings support a transition from simple structural closure toward functional donor-site reconstruction.

Humans

Pollution characteristics and health risks of PAHs and OPAHs in PM2.5 of an inland basin city in China under the influence of the clean air action plan.

Since the implementation of China's Clean Air Action, remarkable progress has been made in air pollution control, with continuous air quality improvement in Xi'an, a typical inland basin city in the Fenwei Plain. To clarify winter organic aerosol pollution variations and pinpoint targeted control needs under policy regulation, this study investigated PM2.5-bound polycyclic aromatic hydrocarbons (PAHs) and oxygenated derivatives (OPAHs) in winter Xi'an, focusing on pollution levels, chemical compositions, source contributions, meteorological impacts, regional transport and health risks. Historical comparison showed generally lower wintertime PAH concentrations in Xi'an during the period of China's clean-air actions. PMF results indicated mixed source influences on PAHs and OPAHs, with biomass-burning-related mixed combustion showing the largest contribution. During haze episodes, absolute concentrations of both PAHs and OPAHs increased; the increase was statistically significant for OPAHs but not for parent PAHs, while 4-5 ring PAHs and BcdPQ dominated the PAH and OPAH profiles, respectively. Meteorological variability, particularly synoptic pressure patterns, was strongly associated with pollutant concentrations, and regional pollution was dominated by in-basin accumulation combined with short-range transport from northern Shaanxi industrial zones. Haze periods exhibited higher toxic-equivalent concentrations, with OPAHs, particularly BcdPQ, dominating the toxicity-equivalent burden. Screening-level ILCR estimates generally remained below 10&#x207b;4 but increased during haze episodes, especially for adult and elderly groups. In conclusion, China's clean air actions have coincided with lower wintertime PAH pollution, but stronger control of residential biomass and other solid-fuel combustion, traffic emissions, and OPAH formation remains necessary in the Fenwei Plain.

China

Initial 4-Year Experience With Microaxial Flow Pumps Within a Tertiary Centre in Regional Australia.

BACKGROUND & AIM: The Microaxial Flow Pump (MFP) is a miniaturised rotary pump that aspirates blood from the left ventricle and expels it into the ascending aorta. It unloads the left ventricle and increases mean arterial pressure and cardiac output. MFP is most commonly utilised in cardiogenic shock, for protected percutaneous coronary intervention (PCI), and for ventricular offloading in veno-arterial extracorporeal membrane oxygenation (VA-ECMO). METHOD: We conducted a retrospective review of all patients who underwent MFP insertion at John Hunter Hospital, Australia. Categorical data are represented as counts and percentages, with continuous variables described as means with standard deviations. RESULTS: Twenty-three MFP devices were inserted between September 2020 and May 2024. Five (22%) were for protected PCI, three (13%) for venting with VA-ECMO (ECPELLA), and 15 (65%) for acute coronary syndrome (ACS) and cardiogenic shock. The median age for the overall cohort was 62 years, with a 74% male predominance. Eighty percent of the protected PCI cohort were elective outpatient procedures, and there were no deaths in this cohort. The mortality in the ECPELLA group was 67%. Thirteen (87%) of the patients with cardiogenic shock presented with an anterior infarct, and 53% had cardiac arrest on admission. The overall morality in the cardiogenic shock cohort was 40%. Complications in this cohort included limb ischaemia in four patients (17%) and site bleeding in seven patients (30%). Four patients (17%) required vascular surgery intervention. CONCLUSION: Our initial experience showed the use of MFP in a tertiary centre was safe and feasible, allowing progression from protected percutaneous intervention to acute cardiogenic shock.

Humans

Bedtime tetrahydrocannabinol ingestion reduces morning orthostatic cardiovascular reactivity in adults: An exploratory study.

Acute cannabis use and its primary psychoactive constituent tetrahydrocannabinol (THC) can induce postural dizziness, indicating increased risk of orthostatic instability. However, it is unknown if vulnerabilities persist the morning after bedtime THC consumption. This study investigated the influence of bedtime THC consumption on cardiovascular variables during an orthostatic challenge. Nine individuals with no cannabis use and eight individuals who regularly use cannabis participated in a tilt table test associated with a 3-day in-laboratory stay. Participants underwent an acclimatization day, followed by a placebo dosing day, and a 10&#x2009;mg THC dosing day. Placebo and THC pills were given 1&#x2009;h before a participant's habitual bedtime, and the tilt table test was performed ~1&#x2009;h upon awakening. Participants were instrumented with an electrocardiogram and an automated sphygmomanometer. Fluid intake and output were measured throughout the study. The morning after THC administration, individuals with no cannabis use reported a higher frequency of dizziness and exhibited a significant reduction in both diastolic blood pressure and heart rate reactivity to tilt (reactivity&#x2009;=&#x2009;tilt - baseline) compared to the morning after placebo. Our results indicate a potential increased risk for orthostatic instability the morning after cannabis consumption in individuals with no cannabis use history.

Humans

Short-term effects of foot reflexology on pain, anxiety, and physiological responses in women with shoulder and neck pain: A randomized controlled trial.

OBJECTIVES: Shoulder and neck pain (SNP) is a common musculoskeletal complaint among women and is often accompanied by heightened anxiety. Foot reflexology (FR) is a complementary therapy proposed to promote relaxation and short-term psychophysiological regulation. This study examined the short-term effects of a single session of FR on pain, anxiety, and physiological responses in women with SNP. METHODS: A single-blind randomized controlled trial was conducted with 80 women aged 20-64&#xa0;years in southern Taiwan. Participants were randomly allocated to one of three groups: FR, exercise, or passive rest control. Each group received a single 50-min session. Pain intensity and anxiety were assessed using the Numeric Rating Scale (NRS) and the State-Trait Anxiety Inventory (STAI), respectively. Heart rate and blood pressure were recorded as physiological indicators. Outcomes were measured at baseline, immediately post-intervention, and at 24-h follow-up. RESULTS: Baseline pain, anxiety, and physiological measures did not significantly differ among groups. Immediately after the intervention, both the FR and exercise groups demonstrated greater reductions in pain intensity compared with the passive rest control (P&#xa0;<&#xa0;0.001 and P&#xa0;=&#xa0;0.018, respectively). The FR group additionally showed greater reductions in anxiety and heart rate compared with the passive rest group (P&#xa0;=&#xa0;0.005 and P&#xa0;=&#xa0;0.001, respectively). Pain reduction in the FR group remained significant at the 24-h follow-up (P&#xa0;=&#xa0;0.013), whereas anxiety reductions were not sustained. No significant between-group differences were observed for systolic blood pressure. CONCLUSION: A single session of FR was associated with immediate and short-term reductions in pain, anxiety, and heart rate among women with SNP. Foot reflexology may serve as a supportive, non-pharmacological approach for short-term modulation, although sustained effects require further investigation.

Humans

Rotavirus vaccine effectiveness against rotavirus and acute gastroenteritis mortality: an analysis of pooled case-control studies from the MNSSTER-V dataset.

BACKGROUND: Rotavirus accounts for an estimated 25% of diarrhoea deaths in children under 5 years globally, and more than 140 countries have included rotavirus vaccines in their routine national infant vaccination programmes. We aimed to calculate rotavirus vaccine effectiveness against rotavirus-positive and all-cause acute gastroenteritis deaths. METHODS: The Multi-National Subpopulations Study to Evaluate Rotavirus Vaccines (MNSSTER-V) dataset combines child-level data from test-negative case-control studies of rotavirus vaccine effectiveness that enrolled children under 5 years of age seeking care for acute gastroenteritis at hospitals or emergency departments in 24 countries between July 1, 2007, and Aug 24, 2023. Children were included in this study if they were: younger than 5 years, met the acute gastroenteritis case definition (had at least three episodes of diarrhoea in a 24-h period, had non-bloody and non-chronic diarrhoea, and were enrolled within 7 days of diarrhoea onset), met vaccine card quality metrics, had vaccine delivery dates if the child was reported to have received a rotavirus vaccine, and had a reported outcome of death or discharge. In-hospital acute gastroenteritis deaths were characterised, and rotavirus vaccine effectiveness against all-cause and rotavirus-positive acute gastroenteritis mortality was calculated using an unconditional logistic regression model with adjustment for national under-5 mortality strata and child's age. Vaccine effectiveness analyses against all-cause and rotavirus-positive acute gastroenteritis mortality were restricted to children aged at least 3 months who received any routine vaccines from countries reporting at least one acute gastroenteritis death. FINDINGS: From the MNSSTER-V dataset, we included 27&#x2008;252 children younger than 5 years enrolled from 22 countries; outcomes of patients were not available for two countries. At least one in-hospital acute gastroenteritis death was reported from 16 countries including 21&#x2008;522 children; in total, 183 all-cause acute gastroenteritis deaths and 25 rotavirus-positive deaths were reported. Among children aged at least 3 months who had received any routine vaccines, receiving at least one dose of a rotavirus vaccine had an adjusted vaccine effectiveness of 75&#xb7;8% (95% CI 28&#xb7;4 to 91&#xb7;8; n=13&#x2008;630) against rotavirus-positive acute gastroenteritis mortality and 20&#xb7;8% (-47&#xb7;0 to 57&#xb7;3; n=20&#x2008;005) against all-cause acute gastroenteritis mortality. INTERPRETATION: Rotavirus vaccines are effective in preventing rotavirus-positive acute gastroenteritis mortality. Continued efforts to improve vaccine delivery could help to reduce acute gastroenteritis mortality due to rotavirus worldwide. FUNDING: None.

Humans

Postoperative hypotony after retinectomy in rhegmatogenous retinal detachment surgery: A systematic review and meta-analysis.

We estimate the incidence of postoperative hypotony after retinectomy performed during rhegmatogenous retinal detachment surgery and explore clinical, surgical, and methodological factors associated with hypotony risk. We include human clinical studies reporting postoperative intraocular pressure (IOP) outcomes after retinectomy or retinotomy for retinal detachment. Postoperative hypotony was defined as IOP &#x2264;&#x202f;6&#x202f;mmHg, with alternative thresholds (&#x2264;5 or &#x2264;3&#x202f;mmHg) retained for sensitivity analyses. A random-effects meta-analysis was used to pool hypotony incidence, with prespecified subgroup and sensitivity analyses according to retinectomy extent, tamponade strategy, hypotony definition, assessment timepoint, and vitrectomy gauge size. Study-level associations with visual outcomes and proliferative vitreoretinopathy (PVR) severity were also explored. Thirty-three studies comprising 2673 eyes were included. The pooled incidence of postoperative hypotony was 13.71% (95% CI, 10.40-17.40), with substantial heterogeneity (I&#xb2; = 83.2%). Hypotony incidence did not increase linearly with retinectomy extent, and similar rates were observed for extents of 180&#xb0;-269&#xb0; and &#x2265;&#x202f;270&#xb0;. Stricter hypotony definitions and later postoperative assessment timepoints were associated with a higher reported incidence. A significant negative association was observed between hypotony incidence and visual improvement rates (Spearman &#x3c1; = -0.47, p&#x202f;=&#x202f;0.03). In contrast, no significant study-level difference in hypotony incidence was observed according to PVR severity grouping or vitrectomy gauge size. Postoperative hypotony after retinectomy is a frequent and clinically relevant complication, moderately associated with poorer visual outcomes and influenced by methodological factors rather than retinectomy extent alone.

Humans

Furanic compounds in different coffee extraction systems: Analysis of the main influencing factors and correlation with acrylamide.

This study investigates how different coffee types representative of distinct roast profiles and brewing methods jointly affect the occurrence of furanic compounds and acrylamide in brewed coffee. Coffees were prepared using eight extraction methods (AeroPress, Clever, Chemex, French Press, Moka, Pure Brew, Turkish and V60). Five furanic compounds (furfural, furfuryl acetate, 5-methylfurfural, furfuryl alcohol and 5-hydroxymethylfurfural) were quantified in coffee powders and brews by HS-SPME-GC-MS, while acrylamide was determined by UHPLC-MS/MS. Moka and Turkish brews consistently exhibited the highest concentrations of furanic compounds, whereas paper-filtered pour-over methods (V60 and Chemex) showed the lowest levels. Pearson correlation analysis revealed coffee-dependent relationships between furanic compounds, acrylamide and extraction parameters with the strongest associations observed in dark-roasted coffee, reflecting advanced Maillard reaction chemistry. Overall, these results demonstrate that contaminant levels arise from the combined effects of intrinsic coffee chemistry and brewing mechanics and support targeted mitigation strategies: such as roast selection and brewing method optimization.

Acrylamide

Acetylcholine signaling regulates osmotic stress adaptation in the phytopathogen Dickeya solani.

Plants impose strong selective pressures that shape both the composition and functional potential of plant microbiomes. The adaptation of plant-associated bacteria to their hosts relies on an extensive repertoire of signal transduction systems that sense plant-derived molecules and dynamically adjust bacterial physiology and metabolism within the holobiont. These signals include key plant signaling compounds that regulate processes essential for plant-microbe interactions. Among them, acetylcholine is emerging as an important signaling molecule in both plants and bacteria. Here, we demonstrate that acetylcholine regulates the expression of the osmotic stress response betIBA gene cluster in the important phytopathogen Dickeya solani, where it plays an important role in osmoprotection. We show that the TetR-family transcriptional regulator associated with this pathway, BetIDs, recognizes acetylcholine as well as choline and trimethylamine. These three ligands differentially induce betIBA transcription in a manner that correlates with their binding affinities. Ligand binding does not affect BetIDs binding to the bet promoter or its oligomeric state. Instead, it induces pronounced changes in the secondary structure of BetIDs, with the magnitude of these conformational changes being ligand-dependent. We further show that quorum sensing modulates osmotic stress tolerance in D. solani by regulating the expression of the Bet pathway. The Bet system is required for the full virulence of D. solani, particularly in chemically complex plant tissues. Phylogenetic analyses reveal that the BetIBA system is widely distributed among plant-associated Pseudomonadota, collectively supporting its importance for bacterial survival and adaptation in plant-related environments.

Osmotic Pressure

The Brazilian contribution to ant toxinology: challenges and perspectives.

Ant toxinology in Brazil is a small but growing field that has revealed wide biochemical diversity and clear potential for bioprospecting therapeutic molecules. This review compiles the Brazilian contribution, focusing on advances in the characterization of venoms from medically and ecologically important species of Dinoponera, Solenopsis, Paraponera, Pachycondyla, Neoponera, and Ectatomma. Brazilian groups applied omics approaches, including transcriptomics and proteomics, to resolve the composition of these venoms and identified peptide-rich arsenals with antimicrobial, antiparasitic, antitumor, and neuroactive activity. Studies of venom phenotypic plasticity showed ecological factors such as diet and seasonality shape venom composition. Two challenges persist: assigning function to still unidentified components and obtaining venom in the quantities that broad analysis requires. The near-term prospects are the rational design of peptide analogues with improved activity and continued bioprospecting of new species, which together position Brazil as a central contributor to ant toxinology.

Animals

Evolution of maize recombination landscape during domestication.

Despite the plethora of knowledge about the benefits of meiotic recombination and numerous theoretical studies examining how recombination rates evolve, there is a general lack of empirical support and consensus across species. To fill this knowledge gap, we characterized the evolution of recombination landscape in maize during its domestication from teosinte and related the observed changes to established theoretical frameworks. Through examining recombination in experimental populations of maize and teosinte and the population genomics approach of identifying historical recombination events using ancestral recombination graph inference to generate saturated maize and teosinte recombination maps, we found that during domestication, maize experienced a 12% increase in its genome-wide recombination rate. Furthermore, maize evolved higher recombination rates on the long arms of chromosomes in regions closer to centromeres, where recombination is generally very low. The repatterning of crossover events came from changes in global crossover positioning rather than alterations in cis-acting chromatin factors. Consequently, we found evidence of selection acting on trans-acting recombination modifiers affecting crossover interference and controlling the interference-dependent class I crossover pathway. We show that CO repatterning was likely beneficial for maize fitness, as significant recombination rate increases were predominantly in gene-rich regions, which harbor domestication-related variation. This work suggests genomic and mechanistic processes leading to the evolution of meiotic recombination landscape in response to directional selection pressure and provides evidence for the evolutionary advantage of recombination.

Zea mays

Safety of insulin eye drops in the treatment of open angle glaucoma: a randomized phase I clinical trial.

OBJECTIVE: The progression of glaucoma despite adequate intraocular pressure (IOP) control highlights the need for neuroprotective and neuroregenerative therapies. Preclinical studies suggest insulin promotes retinal ganglion cell survival and regeneration, but its safety in higher concentrations (100 and 500 units/mL), administered topically, has been poorly characterized in humans. We aim to assess the safety and tolerability of these two concentrations of insulin eye drops in patients with open-angle glaucoma (OAG). DESIGN: A phase I, randomized, double-blind, placebo-controlled, single-centre clinical trial. PARTICIPANTS: Patients with mild to moderate OAG were randomized 2:2:1 to receive once-daily topical insulin U-100, U-500, or placebo in 1 eye for 5 days, with follow-up visits at 1, 3, and 6 months. The primary safety outcomes include glycemia, serum potassium, ocular adverse events (AEs), and ocular tolerability scores. Secondary outcomes included IOP, best-corrected visual acuity (BCVA), retinal nerve fibre layer thickness, ganglion cell complex, visual field, and OCT angiography. RESULTS: Eighteen open-angle glaucoma patients were enrolled (mean age: 66.2 &#xb1; 10.1 years). No serious AEs related to insulin were observed. One asymptomatic, transient near-hypoglycemia event occurred in a fasting participant (3.9 mmol/L), with no recurrence after dietary adjustment. No significant changes were found in serum potassium, IOP, BCVA, visual fields, or OCT. Ocular symptoms in the insulin groups were limited to transient, mild burning sensation upon application. One participant experienced cystoid macular edema at 3 months, which was attributed to pre-existing ocular pathology. CONCLUSION: Topical insulin at 100 and 500 units/mL concentrations was well tolerated in patients for short-term use and did not result in significant systemic or ocular toxicity.

Aged

Glycerophospholipid remodeling under osmotic stress in grass carp gills.

Salinity fluctuations represent a pervasive environmental challenge for freshwater fishes, yet the cellular and metabolic programs governing early osmoregulatory responses remain understudied. Here, we investigated the time-dependent gill responses of juvenile grass carp (Ctenopharyngodon idella) subjected to an acute, sublethal salinity increase 9 parts per thousand (ppt). Histological and biochemical analyses revealed progressive gill lesions accompanied by elevated lactate dehydrogenase (LDH) activity and lipid peroxidation, indicating rapid tissue injury under osmotic stress. Integrative metabolomic and transcriptomic profiling uncovered pronounced temporal reprogramming, consistently highlighting glycerophospholipid metabolism as a central axis of response. In particular, phosphatidylcholine (PC) species exhibited dynamic remodeling, coupled with transcriptional enrichment of lipid turnover, membrane transport, and innate immune pathways. Network-based integration identified a PC-centered remodeling module characterized by accelerated PC headgroup turnover, disruption of the PLA2-LPCAT2 lyso-PC reacylation cycle, and enhanced ABC transporter-associated lipid and sterol export, reflected by cholesteryl sulfate accumulation and a shifted n-6 polyunsaturated fatty acid-derived oxylipin signature. Functional assays further demonstrated that PC and linoleic acid (LA) supplementation improved cell viability and alleviated oxidative stress and pro-inflammatory signaling in grass carp cells under salinity challenge. Collectively, these findings reveal phospholipid-centered membrane remodeling as an early, integrative mechanism linking osmotic stress to gill injury and immune activation in freshwater fish, providing insights into potential strategies of environmental stress adaptation.

Animals

Effects of a programmed reflexology therapy on sleep quality, insomnia, and fatigue among individuals with poor sleep quality: evidence for autonomic nervous system modulation.

Poor sleep quality is closely associated with autonomic dysregulation and increased risks of cardiovascular, metabolic, and mental disorders. Foot reflexology is a widely used complementary therapy; however, its physiological mechanisms and comparative efficacy remain insufficiently explored. This study aimed to compare the effects of manual reflexology treatment (MRT) and foot massage equipment (FEM) on autonomic nervous system function, sleep quality, insomnia severity, and fatigue in adults with poor sleep quality. Using a randomized crossover design, 32 participants with poor sleep quality received MRT and FEM interventions for 6 weeks each (once weekly, 30-40&#x202f;min/session). Heart rate (HR), blood pressure, and heart rate variability (HRV; time- and frequency-domain indices) were assessed at weeks 1 and 6 before and after each intervention. Subjective outcomes included the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), and Fatigue Assessment Scale (FAS). Following MRT, participants demonstrated significantly greater reductions in global PSQI scores and all PSQI components compared with FEM. MRT also resulted in larger improvements in insomnia severity and both mental and physical fatigue. In contrast, FEM primarily improved physical fatigue. Physiologically, MRT induced an immediate decrease in HR and significant increases in HRV time-domain indices (SDNN, RMSSD, pNN50), which were sustained after 6 weeks. Frequency-domain analysis further revealed reduced LF, increased HF, and a lower LF/HF ratio, indicating enhanced parasympathetic activity and cumulative autonomic modulation. In conclusion, programmed manual reflexology, delivered according to the TIDieR framework, is more effective than mechanical foot massage in improving autonomic balance, sleep quality, insomnia severity, and fatigue in individuals with poor sleep quality. These findings support MRT as a feasible and evidence-based non-pharmacological complementary intervention for sleep health promotion. TRIAL REGISTRATION: clinicaltrials.gov; NCT Number: NCT07402460; Registered 3 February 2026.

Adult