Enhancing efficiency of protein language models with minimal wet-lab data through few-shot learning.

Accurately modeling the protein fitness landscapes holds great importance for protein engineering. Pre-trained protein language models have achieved state-of-the-art performance in predicting protein fitness without wet-lab experimental data, but their accuracy and interpretability remain limited. On the other hand, traditional supervised deep learning models require abundant labeled training examples for performance improvements, posing a practical barrier. In this work, we introduce FSFP, a training strategy that can effectively optimize protein language models under extreme data scarcity for fitness prediction. By combining meta-transfer learning, learning to rank, and parameter-efficient fine-tuning, FSFP can significantly boost the performance of various protein language models using merely tens of labeled single-site mutants from the target protein. In silico benchmarks across 87 deep mutational scanning datasets demonstrate FSFP's superiority over both unsupervised and supervised baselines. Furthermore, we successfully apply FSFP to engineer the Phi29 DNA polymerase through wet-lab experiments, achieving a 25% increase in the positive rate. These results underscore the potential of our approach in aiding AI-guided protein engineering.

Folic acid supplementation for stroke prevention: A systematic review and meta-analysis of 21 randomized clinical trials worldwide.

BACKGROUND & AIMS: The AHA/ASA guidelines for primary stroke prevention are almost a decade old. The current recommendation regarding folic acid supplementation is based on only 8 clinical trials, and an additional 13 folate trials have been published since then. This meta-analysis aims to fill in critical evidence gaps by comprehensively evaluating 21 published trials with particular attention given to identifying the true influences through stratification. METHODS: PubMed, the Cochrane Central Register of Controlled Trials, and Embase were searched from inception to April 4, 2023. This study included all randomized controlled trials (RCTs) of folic acid with stroke as one of the reporting endpoints. Relative risks and 95% confidence intervals were used to assess the association between folic acid supplementation and the risk of stroke in a random-effects model. RESULTS: Results from the 21 pooled RCTs totaling 115,559 participants showed that folic acid supplementation significantly reduced the risk of stroke by 10% (RR 0.90, 95%CI 0.83 to 0.98). Subgroup analyses showed that folic acid efficacy was greater in areas without fortified grain or with partially-fortified grain (RR = 0.83, 95% CI 0.75 to 0.93; RR = 1.04 in areas with grain fortification, P-interaction = 0.003). In this group, folic acid supplementation was most efficacious in those without a history of stroke or myocardial infarction (RR = 0.77, 95% CI 0.68 to 0.86; RR = 0.94 for participants with a history of stroke or myocardial infarction, P-interaction = 0.008). The efficacy of folic acid remained consistent regardless of baseline folate levels, folic acid dosage, baseline vitamin B12 levels, vitamin B12 dosage, homocysteine reduction, intervention duration, and whether folic acid was taken alone or in combination (all P-interaction>0.05). All 21 trials were free of attrition bias and reporting bias, and there was no significant publication bias. CONCLUSIONS: This is by far the largest meta-analysis of RCTs regarding folic acid supplementation and stroke, demonstrating the overall benefit of folic acid for stroke prevention. Grain fortification and history of stroke or myocardial infarction may be the most important influences on the efficacy of folic acid for stroke prevention.

[Water use characteristics and the mechanism of water uptake in two typical sand-fixing species in Mu Us sandy land]. / æ¯›ä¹Œç´ å ¸åž‹å›ºæ²™æ¤ç‰©çš„æ°´åˆ†åˆ©ç”¨ç‰¹æ€§ä¸Žå¸æ°´æœºåˆ¶.

Understanding water absorption mechanisms of sand-fixing plants is important for the rational establishment of plant community structures, thereby providing a scientific basis for desertification control and the efficient utilization of water resources in sandy areas. Based on the hydrogen and oxygen isotopic compositions of precipi-tation, soil water, xylem water, and groundwater, coupled with soil water-heat dynamics, annual water consumption characteristics of vegetation, using the multi-source linear mixing model (IsoSource), we analyzed the differences in water sources between Salix psammophila and Artemisia ordosica, during winter and the growing season. We further examined the effects of groundwater depth (2 m and 10 m), soil freezing-thawing, and drought on their water utilization to elucidate water absorption mechanisms of those species. The results showed that: 1) During soil freezing-thawing period (January to March), S. psammophila mainly utilized soil water in 60-120 cm depths below the frozen layer (69.1%). In the green-up season (April and May), soil water from the 0-60 cm layers could satisfy the water demand of S. psammophila (30.9%-87.6%). During the dry period of the growing season (June), it predominantly utilized soil water at the depth of 120-160 cm (27.4%-40.8%). Over the rainy season (July and September), soil water in 0-60 cm depths provided 59.8%-67.9% of the total water required. A. ordosica, with shallow roots, could not utilize soil water after complete freezing of root zone but could overwinter by storing water in rhizomes during autumn. During the growing season, it primarily relied on 0-40 cm soil layer (23.4%-86.8%). During the dry period, it mainly utilized soil water from 40-80 cm and 80-160 cm soil layers, with utilization rates of 14.6%-74.4% and 21.8%-78.2%, respectively. 2) With decreasing groundwater depth, vegetation shifted its water absorption depth upward, with water source of S. psammophila transitioning from 120-160 cm to 60-160 cm layers, while A. ordosica shifted water absorption depth from 80-160 cm to 0-40 cm. S. psammophila's utilization of soil water is influenced by transpiration, adopting an "on-demand" approach to achieve a balance between water supply and energy conservation, whereas A. ordosica tends to utilize shallow soil water, exhibiting a higher depen-dence on water sources from a single soil layer.

Sinensetin, a polymethoxyflavone from citrus fruits, ameliorates LPS-induced acute lung injury by suppressing Txnip/NLRP3/Caspase-1/GSDMD signaling-mediated inflammatory responses and pyroptosis.

Sinensetin (SIN), a polymethoxylated flavonoid, exists widely in citrus fruits with abundant biological activities, such as antioxidant and anti-inflammatory properties, delaying the progression of lung fibers and ameliorating inflammatory lung injury. Herein, an in vivo model of LPS-induced acute lung injury (ALI) in mice and an in vitro model of LPS + IFN-γ-induced M1 polarization in RAW264.7 cells were established to assess the effects and molecular mechanisms of SIN in ameliorating ALI. In the present study, the results showed that SIN significantly reduced BALF IL1ß, IL6, and TNF-α levels and neutrophil infiltration, inhibited lung tissue COX2 and iNOS expression, reduced serum and lung tissue inflammatory factor levels, and attenuated lung tissue inflammatory infiltration and ROS levels in animal experiments. RNA sequencing analysis showed that SIN markedly inhibited the expression of inflammation-related pathway genes such as NOD-like receptor signaling. Further mechanistic studies confirmed that SIN significantly inhibited the dissociation of Txnip and Trx-1 and decreased the expression of NLRP3, ASC, pro-Caspase-1, cleavage Caspase-1 p10, NEK7, Caspase-8, IL1ß, IL18, and GSDMD. Meanwhile, SIN docked to NLRP3 with strong affinity and bound stably in the hydrophobic docking pocket. Similarly, the same results were observed in in vitro macrophage M1 polarization experiments. In conclusion, the results revealed that SIN ameliorated the onset and progression of ALI by inhibiting Txnip/NLRP3/Caspase-1/GSDMD signaling-mediated inflammatory responses and pyroptosis. These findings emphasize the significant role of SIN in ameliorating ALI and provide insights into the strategy for exploring the functional effects of foods.

Methacrylated Carboxymethyl Chitosan Scaffold Containing Icariin-Loaded Short Fibers for Antibacterial, Hemostasis, and Bone Regeneration.

Bone defects typically result in bone nonunion, delayed or nonhealing, and localized dysfunction, and commonly used clinical treatments (i.e., autologous and allogeneic grafts) have limited results. The multifunctional bone tissue engineering scaffold provides a new treatment for the repair of bone defects. Herein, a three-dimensional porous composite scaffold with stable mechanical support, effective antibacterial and hemostasis properties, and the ability to promote the rapid repair of bone defects was synthesized using methacrylated carboxymethyl chitosan and icariin-loaded poly-l-lactide/gelatin short fibers (M-CMCS-SFs). Icariin-loaded SFs in the M-CMCS scaffold resulted in the sustained release of osteogenic agents, which was beneficial for mechanical reinforcement. Both the porous structure and the use of chitosan facilitate the effective absorption of blood and fluid exudates. Moreover, its superior antibacterial properties could prevent the occurrence of inflammation and infection. When cultured with bone mesenchymal stem cells, the composite scaffold showed a promotion in osteogenic differentiation. Taken together, such a multifunctional composite scaffold showed comprehensive performance in antibacterial, hemostasis, and bone regeneration, thus holding promising potential in the repair of bone defects and related medical treatments.

Association of osteoporosis with sarcopenia and its components among community-dwelling older Chinese adults with different obesity levels: A cross-sectional study.

We aimed to investigate whether sarcopenia and its components are associated with osteoporosis in community-dwelling older Chinese adults with different obesity levels. This cross-sectional study included 1938 participants (42.1% male) with a mean age of 72.1 ±â€…5.9 years. The categorization of individuals into various weight categories was based on the Working Group on Obesity in China's criteria, utilizing the body mass index (BMI) as follows: underweight, BMI < 18.5 kg/m2; normal weight, 18.5 ≤ BMI < 24 kg/m2; overweight, 24 ≤ BMI < 28 kg/m2; and obesity, BMI ≥ 28 kg/m2. In this research, the osteoporosis definition put forth by the World Health Organization (bone mineral density T-score less than or equal to -2.5 as assessed by Dual-energy X-ray absorptiometry (DXA)). Sarcopenia was defined according to the diagnostic criteria of the Asian Working Group for Sarcopenia. The prevalence of osteoporosis was highest in the underweight group and gradually decreased with increasing BMI (Underweight: 55.81% vs Normal weight: 45.33% vs Overweight: 33.69% vs Obesity: 22.39). Sarcopenia was associated with elevated odds of osteoporosis in normal-weight subjects independent of potential covariates (OR = 1.70, 95% CI = 1.22-2.35, P = .002). In normal-weight participants, a higher appendicular skeletal muscle mass index (ASMI) was associated with a reduced risk of osteoporosis (OR = 0.56, 95% CI = 0.42-0.74, P < .001). In this study, we found that the prevalence of osteoporosis was highest in the underweight group and gradually decreased with increasing BMI. Sarcopenia, body fat percentage, and ASMI were associated with elevated odds of osteoporosis in normal-weight subjects independent of potential covariates, and higher percent body fat (PBF) was associated with an increased risk of osteoporosis in overweight people, and no such association was found in other weight groups. Different amounts of adipose tissue and muscle mass may alter bone biology. Further longitudinal follow-up studies are required to more accurately assess the risk of osteoporosis and sarcopenia in different weight populations. This cross-sectional study found that the prevalence of osteoporosis was highest in the underweight group and gradually decreased with increasing BMI. Sarcopenia was associated with elevated odds of osteoporosis in normal-weight subjects independent of potential covariates.

In Vitro Activitiy of Rezafungin in Comparison with Anidulafungin and Caspofungin against Invasive Fungal Isolates (2017 to 2022) in China.

The efficacy of different echinocandins is assessed by evaluating the in vitro activity of a novel antifungal, rezafungin, against invasive fungal isolates in comparison with anidulafungin and caspofungin. Using the broth microdilution (BMD) method, the susceptibility of 1000 clinical Candida isolates (including 400 C. albicans, 200 C. glabrata, 200 C. parapsilosis, 150 C. tropicalis and 50 C. krusei) and 150 Aspergillus isolates (100 A. fumigatus and 50 A. flavus) from the Eastern China Invasive Fungi Infection Group (ECIFIG) was tested for the antifungals including anidulafungin, rezafungin, caspofungin and fluconazole. The echinocandins showed strong activity against C. albicans that was maintained against fluconazole-resistant isolates. The GM MIC (geometric mean minimum inhibitory concentration) value of rezafungin was found to be comparable to that of anidulafungin or caspofungin against the five tested common Candida species. C. tropicalis exhibited higher resistance rates (about 8.67-40.67% in different antifungals) than the other four Candida species. Through the sequencing of FKS genes, we searched for mutations in echinocandin-resistant C. tropicalis isolates and found that all displayed alterations in FKS1 S654P. The determined MEC (minimal effective concentration) values against A. fumigatus and A. flavus for rezafungin (0.116 µg/mL, 0.110 µg/mL) are comparable to those of caspofungin (0.122 µg/mL, 0.142 µg/mL) but higher than for anidulafungin (0.064 µg/mL, 0.059 µg/mL). Thus, the in vitro activity of rezafungin appears comparable to anidulafungin and caspofungin against most common Candida and Aspergillus species. Rezafungin showed higher susceptibility rates against C. glabrata. Rezafungin indicates its potent activity for potential clinical application.

The resistance change and stress response mechanisms of chlorine-resistant bacteria under microplastic stress in drinking water distribution system.

The presence of both chlorine-resistant bacteria (CRB) and microplastics (MPs) in drinking water distribution systems (DWDS) poses a threat to water quality and human health. However, the risk of CRB bio evolution under the stress of MPs remains unclear. In this study, polypropylene (PP) and polyethylene (PE) were selected to study the adsorption and desorption behavior of sulfamethoxazole (SMX), and it was clear that MPs had the risk of carrying pollutants into DWDS and releasing them. The results of the antibiotic susceptibility test and disinfection experiment confirmed that MPs could enhance the resistance of CRB to antibiotics and disinfectants. Bacteria epigenetic resistance mechanisms were approached from multiple perspectives, including physiological and biochemical characteristics, as well as molecular regulatory networks. When MPs enter DWDS, CRB could attach to the surface of MPs and directly interact with both MPs and the antibiotics they release. This attachment process promoted changes in the composition and content of extracellular polymers (EPS) within cells, enhanced surface hydrophobicity, stimulated oxidative stress function, and notably elevated the relative abundance of certain antibiotic resistance genes (ARGs). This study elucidates the mechanism by which MPs alter the intrinsic properties of CRB, providing valuable insights into the effective avoidance of biological risks to water quality during CRB evolution.

Serum S-adenosylhomocysteine levels are associated with first stroke in Chinese adults with hypertension.

BACKGROUND: The association between S-adenosylhomocysteine (SAH) and stroke has not been confirmed due to the specialized equipment and time requirements necessary for S-adenosylhomocysteine testing. We aimed to explore the association between SAH and stroke. METHODS: A nested, case-control study drawn from the China Stroke Primary Prevention Trial of rural adults with hypertension, including 557 first stroke cases and 557 matched controls was conducted. Serum SAH was measured by stable-isotope dilution liquid chromatography-tandem mass spectrometry using 4500MD. Multiple conditional logistic regression models were used to evaluate the association between SAH and first stroke. RESULTS: In females, SAH levels were significantly higher in the stroke population than in the control group (16.0 ng/mL vs. 14.6 ng/mL). When SAH was assessed as quartiles, the odds of stroke were 1.78 (95 % CI: 1.02-3.09) in Quartile 2, 1.31 (95 % CI: 0.73-2.33) in Quartile 3, and 1.93 (95 % CI: 1.03-3.62) in Quartile 4, compared to Quartile 1. When Quartiles 2-4 were combined, the adjusted odds ratio of first stroke was 1.64 (95 % CI: 1.03-2.62) compared with Quartile 1. In subgroup analysis, a significant SAH-stroke association was observed in the lower vitamin D3 group (OR = 3.35, 95 % CI:1.72-6.53; P interaction, 0.035). In males, higher levels of SAH were associated with an increased risk of stroke in those under age 60. Compared with the reference group, the adjusted odds ratio of total stroke was 2.40 (95 % CI: 1.02-5.91) in the combined group (Quartile 2-4). In contrast, no significant association between SAH and stroke was found in males aged 60 or older. CONCLUSIONS: This study reveals that SAH is associated with a higher risk of stroke independently of homocysteine, especially in females. SAH may be a second predictor of stroke in the metabolic pathway of methionine, after homocysteine.

Self-Limiting Phase Transition Enabling Reversible Overstoichiometric Li Storage in Ni-Rich Cathodes.

Ni-rich cathodes are some of the most promising candidates for advanced lithium-ion batteries, but their available capacities have been stagnant due to the intrinsic Li+ storage sites. Extending the voltage window down can induce the phase transition from O3 to 1T of LiNiO2-derived cathodes to accommodate excess Li+ and dramatically increase the capacity. By setting the discharge cutoff voltage of LiNi0.6Co0.2Mn0.2O2 to 1.4 V, we can reach an extremely high capacity of 393 mAh g-1 and an energy density of 1070 Wh kg-1 here. However, the phase transition causes fast capacity decay and related structural evolution is rarely understood, hindering the utilization of this feature. We find that the overlithiated phase transition is self-limiting, which will transform into solid-solution reaction with cycling and make the cathode degradation slow down. This is attributed to the migration of abundant transition metal ions into lithium layers induced by the overlithiation, allowing the intercalation of overstoichiometric Li+ into the crystal without the O3 framework change. Based on this, the wide-potential cycling stability is further improved via a facile charge-discharge protocol. This work provides deep insight into the overstoichiometric Li+ storage behaviors in conventional layered cathodes and opens a new avenue toward high-energy batteries.

Impacts of cadmium accumulation on the diversity, assembly processes, and co-occurrence patterns of archaeal communities in marine sediments.

There is limited understanding regarding the changes in the ecological processes and the mechanisms of archaeal community in response to heavy metal contamination in the marine sediments. In this study, sediment samples were collected from 46 locations near harbors, and the concentration of heavy metals and the diversity of archaeal communities were investigated to understand the impact of Cd on archaeal communities. The results demonstrated a significant correlation between the diversity of archaeal community and Cd concentration, particularly showing a linear decrease in the species richness with rising Cd concentration. ANME-1b was identified as a significantly enriched archaeal taxon in the higher Cd environment. Null model and neutral community model indicated that the ecological assembly of archaeal communities in marine sediments was primarily governed by the stochastic processes, with dispersal limitation being the primary factor. The contribution of deterministic process to the assembly of archaeal communities in higher Cd environments increased clearly, accompanied by a notable reduction in species migration rates and widths of ecological niche of archaeal populations. Co-occurrence network analysis revealed an obvious increase in species interactions in higher Cd environments, with an apparent rise in the proportion of competitive relationships and an increase in the number of keystone species. Moreover, archaeal species formed a more complex and stable community to cope with Cd stress. This study provides new insights into the impacts of heavy metals on the ecological processes of marine microorganisms and the underlying mechanisms.

A Horn Peptide-Thermoresponsive Hydrogel for Angiogenesis and Bone Regeneration.

The management of critical-sized bone defects presents a formidable clinical challenge, especially given the increasing incidence of bone diseases in the aging population. Consequently, there is an increased demand for minimally invasive bone repair materials that can effectively address this challenge, particularly in outpatient settings. In this study, the goal is to develop an injectable and biodegradable biomaterial that adheres to and fills bone-defect sites to support bone regeneration. The osteogenic and angiogenic activities of animal horn peptides are investigated by incorporating them into biologically active moieties, in combination with a novel thermosensitive hydrogel. The resulting thermosensitive hydrogel exhibited essential biological functionalities, allowing precise modulation of its physical and chemical properties. Notably, the hydrogel incorporating the horn peptide rapidly filled the bone defect site, promoting both angiogenesis and bone induction. Consequently, this approach significantly accelerates new bone regeneration. In summary, the findings of this study present a promising, minimally invasive solution for addressing critical-sized bone defects.

Optimal folic acid dosage in lowering homocysteine: Precision Folic Acid Trial to lower homocysteine (PFAT-Hcy).

BACKGROUND: While folic acid (FA) is widely used to treat elevated total homocysteine (tHcy), promoting vascular health by reducing vascular oxidative stress and modulating endothelial nitric oxide synthase, the optimal daily dose and individual variation by MTHFR C677T genotypes have not been well studied. Therefore, this study aimed to explore the efficacy of eight different FA dosages on tHcy lowering in the overall sample and by MTHFR C677T genotypes. METHODS: This multicentered, randomized, double-blind, controlled clinical trial included 2697 eligible hypertensive adults with elevated tHcy (≥ 10 mmol/L) and without history of stroke and cardiovascular disease. Participants were randomized into eight dose groups of FA combined with 10 mg enalapril maleate, taken daily for 8 weeks of treatment. RESULTS: The intent to treat analysis included 2163 participants. In the overall sample, increasing FA dosage led to steady tHcy reduction within the FA dosing range of 0-1.2 mg. However, a plateau in tHcy lowering was observed in FA dose range of 1.2-1.6 mg, indicating a ceiling effect. In contrast, FA doses were positively and linearly associated with serum folate levels without signs of plateau. Among MTHFR genotype subgroups, participants with the TT genotype showed greater efficacy of FA in tHcy lowering. CONCLUSIONS: This randomized trial lent further support to the efficacy of FA in lowering tHcy; more importantly, it provided critically needed evidence to inform optimal FA dosage. We found that the efficacy of FA in lowering tHcy reaches a plateau if the daily dosage exceeds 1.2 mg, and only has a small gain by increasing the dosage from 0.8 to 1.2 mg. GOV IDENTIFIER: NCT03472508 (Registration Date: March 21, 2018).

Dosage exploration of combined B-vitamin supplementation in stroke prevention: a meta-analysis and systematic review.

BACKGROUND: The optimal dosage range for B-vitamin supplementation for stroke prevention has not received sufficient attention. OBJECTIVE: Our aim was to determine the optimal dosage range of a combination of folic acid, vitamin B12, and vitamin B6 supplementation in stroke prevention. METHODS: We searched PubMed, the Cochrane Central Register of Controlled Trials, and Embase database for randomized controlled trials published between January 1966 and April 2023, whose participants received B-vitamin supplementation and that reported the number of stroke cases. Relative risk (RR) was used to measure the effect of combined supplementation on risk of stroke using a fixed-effects model. Risk of bias was assessed with the Cochrane risk-of-bias algorithm. RESULTS: The search identified 14 randomized controlled trials of folic acid combined with vitamin B12 and vitamin B6 supplementation for stroke prevention that included 76,664 participants with 2720 stroke cases. In areas without and with partial folic acid fortification, combined B-vitamin supplementation significantly reduced the risk of stroke by 34% [RR: 0.66; 95% confidence interval (CI): 0.50, 0.86] and 11% (RR: 0.89; 95% CI: 0.79, 1.00), respectively. Further analysis showed that a dosage of folic acid ≤0.8 mg/d and vitamin B12 ≤0.4 mg/d was best for stroke prevention (RR: 0.65; 95% CI: 0.48, 0.86) in these areas. In contrast, no benefit of combined supplementation was found in fortified areas (RR: 1.04; 95% CI: 0.94, 1.16). CONCLUSIONS: Our meta-analysis found that the folic acid combined with vitamin B12 and vitamin B6 supplementation strategy significantly reduced the risk of stroke in areas without and with partial folic acid fortification. Combined dosages not exceeding 0.8 mg/d for folic acid and 0.4 mg/d for vitamin B12 supplementation may be more effective for populations within these areas. This trial was registered at PROSPERO asCRD42022355077.

Role of C/EBP Homologous Protein in Vascular Stenosis After Carotid Artery Injury.

The study aims to explore the fluctuating expression of C/EBP Homologous Protein (CHOP) following rat carotid artery injury and its central role in vascular stenosis. Using in vivo rat carotid artery injury models and in vitro ischemia and hypoxia cell models employing human aortic endothelial cells (HAECs) and vascular smooth muscle cells (T/G HA-VSMCs), a comprehensive investigative framework was established. Histological analysis confirmed intimal hyperplasia in rat models. CHOP expression in vascular tissues was assessed using Western blot and immunohistochemical staining, and its presence in HAECs and T/G HA-VSMCs was determined through RT-PCR and Western blot. The study evaluated HAEC apoptosis, inflammatory cytokine secretion, cell proliferation, and T/G HA-VSMCs migration through Western blot, ELISA, CCK8, and Transwell migration assays. The rat carotid artery injury model revealed substantial fibrous plaque formation and vascular stenosis, resulting in an increased intimal area and plaque-to-lumen area ratio. Notably, CHOP is markedly elevated in vessels of the carotid artery injury model compared to normal vessels. Atorvastatin effectively mitigated vascular stenosis and suppresses CHOP protein expression. In HAECs, ischemia and hypoxia-induced CHOP upregulation, along with heightened TNFα, IL-6, caspase3, and caspase8 levels, while reducing cell proliferation. Atorvastatin demonstrated a dose-dependent suppression of CHOP expression in HAECs. Downregulation of CHOP or atorvastatin treatment led to reduced IL-6 and TNFα secretion, coupled with augmented cell proliferation. Similarly, ischemia and hypoxia conditions increased CHOP expression in T/G HA-VSMCs, which was concentration-dependently inhibited by atorvastatin. Furthermore, significantly increased MMP-9 and MMP-2 concentrations in the cell culture supernatant correlated with enhanced T/G HA-VSMCs migration. However, interventions targeting CHOP downregulation and atorvastatin usage curtailed MMP-9 and MMP-2 secretion and suppressed cell migration. In conclusion, CHOP plays a crucial role in endothelial injury, proliferation, and VSMCs migration during carotid artery injury, serving as a pivotal regulator in post-injury fibrous plaque formation and vascular remodeling. Statins emerge as protectors of endothelial cells, restraining VSMCs migration by modulating CHOP expression.

Apoptotic Vesicles Modulate Endothelial Metabolism and Ameliorate Ischemic Retinopathy via PD1/PDL1 Axis.

Pathological angiogenesis with subsequent disturbed microvascular remodeling is a major cause of irreversible blindness in a number of ischemic retinal diseases. The current anti-vascular endothelial growth factor therapy can effectively inhibit angiogenesis, but it also brings significant side effects. The emergence of stem cell derived extracellular vesicles provides a new underlining strategy for ischemic retinopathy. Apoptotic vesicles (apoVs) are extracted from stem cells from human exfoliated deciduous teeth (SHED). SHED-apoVs are delivered into the eyeballs of oxygen-induced retinopathy (a most common model of angiogenic retinal dieseases) mice through intravitreal injection. The retinal neovascularization and nonperfusion area, vascular structure, and density changes are observed during the neovascularization phase (P17) and vascular remodeling phase (P21), and visual function is measured. The expression of extracellular acidification rate and lactic acid testing are used to detect endothelial cells (ECs) glycolytic activity. Furthermore, lentivirus and neutralizing antibody are used to block PD1-PDL1 axis, investigating the effects of SHED-apoVs on glycolysis and angiogenic activities. This work shows that SHED-apoVs are taken up by ECs and modulate the ECs glycolysis, leading to the decrease of abnormal neovessels and vascular remodeling. Furthermore, it is found that, at the molecular level, apoVs-carried PD1 interacts with PDL1 on hypoxic ECs to regulate the angiogenic activation. SHED-apoVs inhibit pathological angiogenesis and promote vascular remodeling in ischemic retinopathy partially by modulating ECs glycolysis through PD1/PDL1 axis. This study provides a new potential strategy for the clinical treatment of pathological retinal neovascularization.

Antimony mobility in soil near historical waste rock at the world's largest Sb mine, Central China.

Soil near waste rock often contains high concentrations of antimony (Sb), but the mechanisms that mobilize Sb in a soil closely impacted by the waste rock piles are not well understood. We investigated these mobility mechanisms in soils near historical waste rock at the world's largest Sb mine. The sequential extraction (BCR) of soil reveal that over 95 % Sb is present in the residual fraction. The leached Sb concentration is related to the surface protonation and deprotonation of soil minerals. SEM-EDS shows Sb in the soil is associated with Fe and Ca. Moreover, X-ray absorption spectroscopy (XAS) results show Sb is predominantly present as Sb(V) and is associated with Fe in the form of tripuhyite (FeSbO4) as well as edge- and corner-sharing complexes on ferrihydrite and goethite. Thus, Fe in soils is important in controlling the mobility of Sb via surface complexation and co-precipitation of Sb by Fe oxides. The initially surface-adsorbed Sb(V) or co-precipitation is likely to undergo a phase transformation as the Fe oxides age. In addition, Sb mobility may be controlled by small amounts of calcium antimonate. These results further the understanding of the effect of secondary minerals in soils on the fate of Sb from waste rock weathering and inform source treatment for Sb-contaminated soils.

Interaction between hypertension and frailty and their impact on death risk in older adults: a follow-up study.

BACKGROUND: Hypertension and frailty often occur concurrently, exhibiting increasing prevalence in the older population. In this study, we analyzed the frailty status among older adults with hypertension and the impact of their interaction on death risk. METHOD: This prospective cohort survey study included data from older people in an urban community in Beijing collected between 2009 and 2020 using the cluster random sampling method. The participants were older adults who were ≥ 60 years old at the time of investigation and had lived at the place of investigation for > 1 year. The survey variables comprised those related to health and frailty status assessed during the 2009 baseline survey, along with death-related information as outcome variables in 2020. Additionally, a frailty index (FI) model was used to examine the frailty status among the older adults at baseline. The effects of hypertension prevalence on the age-related frailty changes as well as on mortality for varying degrees of frailty were further analyzed. Lastly, Cox regression and Kaplan-Meier curves were applied to evaluate the impact of the interaction between hypertension and frailty on death risk. RESULTS: Ultimately, 1197 older individuals aged between 60 and 101 years(average age at baseline: 74.8 ± 8.6 years) were included .Among them, 475 individuals were men (mean age:74.8 ± 8.8 years), and 722 were women (mean age:74.8 ± 8.4 years).Frailty was identified in 151 individuals, leading to a prevalence rate of 12.6%(151/1197),while hypertension was detected in 593 (prevalence rate:49.5% [593/1197]).A total of 443 deaths were recorded by 2020, resulting in a mortality rate of 37.0% (443/1197).Moreover, FI values and mortality rates were higher at any age in older adults with hypertension compared with those without hypertension. Survival time analysis showed that the median survival time of older adults with hypertension and frailty was the shortest (39.0[95%CI: 35.6-42.3] months)when compared with that of older adults without hypertension but with frailty (52.9 [95%CI: 46.6-59.3] months), those with hypertension but without frailty (102.7 [95%CI: 98.7-106.8] months), and those without hypertension and frailty (127.9 [95%CI: 113.5-134.7] months),with log-rank x2 = 999.686 and P < 0.001. Furthermore, Cox regression results demonstrated that older adults with hypertension and frailty had the highest death risk when compared with that of older adults without hypertension and frailty (HR = 1.792, P < 0.001), those without hypertension but with frailty (HR = 1.484, P < 0.001), and those with hypertension but without frailty (HR = 1.406, P = 0.005). CONCLUSION: Frailty is prevalent among older adults with hypertension; however, older adults with both hypertension and frailty have a relatively higher mortality risk. Therefore, screening and assessment of frailty in the older population with hypertension are crucial for its early identification, thereby enabling timely and appropriate interventions to prevent or delay the adverse effects of this concurrent condition.

Selective Adsorption Behavior of Sulfuric Acid Oxidized and Doped Conjugated Microporous Poly(aniline)s toward Lead Ions in an Aqueous Environment.

The coexistence of lead, zinc, and copper ions in wastewater constitutes an environmental challenge of pressing concern. This research delves into the preparation of innovative oxidation-doped conjugated microporous poly(aniline) frameworks, exploring their prospective efficacy in regulating lead ion adsorption from aqueous solutions. H2SO4-CMPTA demonstrates the capability to reach adsorption equilibrium within 15 min at a lead concentration of 50 ppm. Even at a lead concentration of 20 ppm, it still efficaciously attenuates these levels to sub-10 ppb, a value surpassing extant standard. H2SO4-CMPTA retains over 78.8% adsorption efficiency after six cycles. Analytical characterization coupled with computational calculations suggests that sulfate-coordinated nitrogen cationic structure plays a crucial role in adsorption. A deeper investigation reveals the cardinal role of electrostatic attraction and exclusive chelation adsorption underpinning the efficient capture of lead ions by doped sulfate ions. Intriguingly, in a mixed heavy metal solution containing lead, zinc, and copper ions, H2SO4-CMPTA exhibits an initial predilection toward zinc ions, yet an eventual ion-exchange adsorption gravitating toward lead ions was discerned, governed by the latter's superior binding energy. Our study elucidates a promising material as an efficacious tool for the remediation of aquatic environments tainted with lead contaminants.