A comparative evaluation of bioequivalence of Gan & Lee glargine U300 and Toujeo® in Chinese healthy male participants.

Background: To assess the bioequivalence between Gan & Lee (GL) glargine U300 and Toujeo® regarding pharmacokinetics (PK), pharmacodynamics (PD), and safety in Chinese healthy male participants. Methods: A single-center, randomized, double-blind, single-dose, two-preparation, two-sequence, four-cycle repeated crossover design study was performed to compare GL glargine U300 and Toujeo® in 40 healthy participants. The primary PK endpoints were the area under the curve of glargine metabolites, M1 concentration from 0 to 24 hours (AUC0-24h), and the maximum glargine concentration within 24 hours post-dose (Cmax). The primary PD endpoints were the area under the glucose infusion rate (GIR) curve from 0 to 24 hours (AUCGIR.0-24h) and the maximum GIR within 24 hours post-dose (GIRmax). Results: GL Glargine U300 demonstrated comparable PK parameters (AUC0-24h, Cmax, AUC0-12h, and AUC12-24h of M1) and PD responses [AUCGIR.0-24h, GIRmax, AUCGIR.0-12h, and AUCGIR.12-24h] to those of Toujeo®, as indicated by 90% confidence intervals ranging from 80% to 125%. No significant disparities in safety profiles were observed between the two treatment groups, and there were no reported instances of serious adverse events. Conclusion: The PK, PD, and safety of GL glargine U300 were bioequivalent to that of Toujeo®. Clinical trial registration: https://www.chinadrugtrials.org.cn/, identifier CTR20212419.

Plin4 exacerbates cadmium-decreased testosterone level via inducing ferroptosis in testicular Leydig cells.

Strong evidence indicates that environmental stressors are the risk factors for male testosterone deficiency (TD). However, the mechanisms of environmental stress-induced TD remain unclear. Based on our all-cause male reproductive cohort, we found that serum ferrous iron (Fe2⁺) levels were elevated in TD donors. Then, we explored the role and mechanism of ferroptosis in environmental stress-reduced testosterone levels through in vivo and in vitro models. Data demonstrated that ferroptosis and lipid droplet deposition were observed in environmental stress-exposed testicular Leydig cells. Pretreatment with ferrostatin-1 (Fer-1), a specific ferroptosis inhibitor, markedly mitigated environmental stress-reduced testosterone levels. Through screening of core genes involved in lipid droplets formation, it was found that environmental stress significantly increased the levels of perilipins 4 (PLIN4) protein and mRNA in testicular Leydig cells. Further experiments showed that Plin4 siRNA reversed environmental stress-induced lipid droplet deposition and ferroptosis in Leydig cells. Additionally, environmental stress increased the levels of METTL3, METTL14, and total RNA m6A in testicular Leydig cells. Mechanistically, S-adenosylhomocysteine, an inhibitor of METTL3 and METTL14 heterodimer activity, restored the abnormal levels of Plin4, Fe2⁺ and testosterone in environmental stress-treated Leydig cells. Collectively, these results suggest that Plin4 exacerbates environmental stress-decreased testosterone level via inducing ferroptosis in testicular Leydig cells.

U-shaped association between pan-immune-inflammation value and periodontitis: NHANES 2009-2014.

BACKGROUND: This study aimed to investigate the relationship between the pan-immune-inflammation value (PIV) and periodontitis based on a large national survey. METHODS: In the present cross-sectional study, data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2009-2014, which included a total of 10,300 participants. The categorization of periodontitis was based on the 2017 classification scheme. The PIV was determined using the formula: (neutrophils count × monocyte count × platelet count)/lymphocytes count. Restricted cubic spline and weighted multivariable logistic regression analyses were employed to evaluate the associations between the PIV with periodontitis. RESULTS: The associations between PIV and stage III/IV periodontitis followed a U-shaped pattern (Pnon-linearity < 0.001). The risk of developing stage III/IV periodontitis showed an increasing trend among participants in the first quartile (odds ratio [OR] = 1.21; 95% confidence interval [CI]: 1.01-1.46), third quartile (OR = 1.34; 95% CI: 1.11-1.61), and fourth quartile (OR = 1.47; 95% CI: 1.25-1.73) compared to those in the second quartile. Subgroup analysis indicated stronger associations of PIV with periodontitis in males (ORQ4vs2 = 1.72, 95% CI: 1.36-2.18) and individuals with hypertension (ORQ4vs2 = 1.78, 95% CI: 1.38-2.28) with significant interactions (Pinteraction < 0.05). CONCLUSIONS: There is a U-shaped association between PIV and stage III/IV periodontitis, which suggests a potential adjunctive treatment strategy for periodontitis. Higher PIV values were found to have a stronger correlation with stage III/IV periodontitis in males and individuals with hypertension. Further prospective trials are needed to confirm the validity of our results. PLAIN LANGUAGE SUMMARY: A U-shaped association exists between the pan-immune inflammation value and periodontitis in US adults, suggesting that maintaining a moderate immune inflammation response is crucial for periodontal health.

The influence factors on pit and fissure sealing behavior of 12-year-old children: a cross-sectional study in Zhejiang, China.

BACKGROUND: In the 21st century, dental caries remains a global burden, particularly severely affecting the growth and quality of life of 12-year-old children. Fortunately, pit and fissure sealing (PFS) procedures can effectively prevent molars from caries. Hence, this study focused on the relationship between PFS and oral epidemiological factors in 12-year-old children. METHODS: A cross-sectional survey was conducted in 12-year-old children from 11 cities in Zhejiang Province. Their dental conditions were collected through questionnaires, as well as basic information such as relevant family information, oral health knowledge and behavior. Then, logistic regression analysis was used to identify the influencing factors associated with PFS. RESULTS: A total of 1204 children were included, with 252 in the PFS group and 952 in the non-PFS group. There were significant differences between the two groups in terms of decayed, missing and filled teeth (DMFT) score, first permanent molar DMFT score, residential area, educational level of parents, tooth-brushing frequency, use of dental floss, oral examination in a medical institution, having taken courses on oral health care, as well as having knowledge that tooth brushing could effectively prevent gingival inflammation, PFS could protect teeth, and oral disease may affect general health. According to further logistic regression analysis, the independent factors influencing PFS included use of dental floss [odds ratios (OR) = 1.672, 95% confidence intervals (CI) = 1.235-2.263, P = 0.001], having taken courses on oral health care (OR = 0.713, 95% CI = 0.515-0.988, P = 0.042), having knowledge that tooth brushing is effective in preventing gingival inflammation (OR = 0.627, 95% CI = 0.389-0.987, P = 0.044) and having knowledge that PFS can protect teeth (OR = 0.589, 95% CI = 0.438-0.791, P < 0.001). CONCLUSION: PFS can reduce the mean DMFT score of 12-year-old children. Independent influencing factors of PFS consist of use of dental floss, having taken courses on oral health care, oral health behavior and knowledge level.

[Advance of research on 22q11.2 deletion syndrome].

22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal microdeletion disorder. Its phenotype is highly variable with incomplete penetrance. 22q11.2DS is a rare disease, and the research progress is relatively slow, which has restricted its treatment and intervention. In recent years, much progress has been made in the pathogenic mechanism and genome-wide association study of 22q11.2DS. In this review, the pathogenesis of 22q11.2DS was summarized. Thereafter, the molecular and pathological mechanisms of TBX1 and DGCR8 genes were clarified. Finally, factors affecting the penetrance of cardiac and immune system phenotypes were reviewed. This review may enhance the understanding of 22q11.2DS and has important clinical implications on the prenatal diagnosis, genetic counseling, treatment and intervention of this disease.

Sulfate Derivatives with Heteroleptic Tetrahedra: New Deep-ultraviolet Birefringent Materials in which Weak Interactions Modulate Functional Module Ordering.

Deep-ultraviolet (UV) birefringent materials are urgently needed to facilitate light polarization in deep-UV lithography. Maximizing anisotropy by regulating the alignment of functional modules is essential for improving the linear optical performance of birefringent materials. In this work, we proposed a strategy to design deep-UV birefringent materials that achieve functional module ordering via weak interactions. Following this strategy, four compounds CN4H7SO3CF3, CN4H7SO3CH3, C(NH2)3SO3CH3, and C(NH2)3SO3CF3 were identified as high-performance candidates for deep-UV birefringent materials. The millimeter-sized crystals of CN4H7SO3CF3, CN4H7SO3CH3, and C(NH2)3SO3CH3 were grown, and the transmittance spectra show that their cutoff edges are below 200 nm. CN4H7SO3CF3 exhibits the largest birefringence (0.149 @ 546 nm, 0.395 @ 200 nm) in the deep-UV region among reported sulfates and sulfate derivatives. It reveals that the hydrogen bond can modulate the module ordering of the heteroleptic tetrahedra and planar π-conjugated cations, thus greatly enhancing the birefringence. Our study not only discovers new deep-UV birefringent materials but also provides an upgraded strategy for optimizing optical anisotropy to achieve efficient birefringence.

Efficacy analysis of ALK inhibitors for treating lung squamous carcinoma patients harboring ALK rearrangement.

Background: Anaplastic lymphoma kinase (ALK)-rearranged pulmonary squamous cell carcinoma (SCC) is a rare subtype of non-small cell lung cancer and the treatment options are limited. We aimed to evaluate the efficacy of ALK tyrosine kinase inhibitors (TKIs) in advanced lung SCC patients with ALK rearrangement. Methods: We collected 11 primary lung SCC samples at the Zhejiang Cancer Hospital between March 2015 and October 2022. In addition, we conducted a literature search of previous studies, and a pooled analysis of 34 patients was performed. The Kaplan-Meier method was applied to generate progression-free survival (PFS) and overall survival (OS) curves, and a log-rank test was used to compare PFS and OS curves for different subgroups. Results: A pooled analysis of 36 patients was performed. Nineteen patients (52.8%) achieved partial response and 9 (25.0%) had stable disease. The objective response rate was 52.8%, and the disease control rate was 77.8%. The median PFS was 7.10 months. Further, alectinib was not superior to crizotinib in prolonging PFS (9.00 vs. 6.00 months, P=0.60). The median PFS of patients receiving initial ALK TKIs as the first-line therapy and second- or further-line therapy was 9.00 and 6.00 months (P=0.26), respectively. Conclusions: Patients with ALK-rearranged lung SCC obtained moderate benefit from ALK-inhibitor therapy. Compared with crizotinib, alectinib did not show superior efficacy in the treatment of ALK-positive lung SCC. Further high-quality trials are warranted.

Safety of Antiplatelet Therapy in Noncardioembolic Ischemic Stroke With Thrombocytopenia: The CASE II Study.

BACKGROUND: There is scant evidence regarding the safety of antiplatelet therapy in acute ischemic stroke (AIS) patients with thrombocytopenia. Our study aims to address this concern by examining AIS patients with thrombocytopenia from a large database in real-world settings. METHODS AND RESULTS: We included patients with AIS with a platelet count <100×109/L who had complete records of antiplatelet drug use. Those requiring anticoagulation or having contraindications to antiplatelet therapy were excluded. Short-term safety outcomes were in-hospital bleeding events, while the long-term safety outcome was 1-year all-cause mortality. A good clinical outcome was defined as functional independence, indicated by a modified Rankin Scale score of 0 to 2 at discharge. Propensity score matched analyses were used. We screened 169 423 patients with AIS from 90 stroke centers in the CASE II register, ultimately enrolling 2808 noncardioembolic patients with thrombocytopenia. In the propensity score matched analyses, no significant difference was observed between the antiplatelet and nonantiplatelet groups in terms of intracranial hemorrhage (odds ratio=0.855 [95% CI, 0.284-5.478]; P=0.160) or gastrointestinal bleeding (odds ratio=2.034 [95% CI, 0.755-5.478]; P=0.160). Antiplatelet therapy was associated with improved functional outcomes at discharge (odds ratio=1.405 [95% CI, 1.028-1.920]; P=0.033), and showed a trend towards reducing 1-year mortality (odds ratio=0.395 [95% CI, 0.152-1.031]; P=0.058). CONCLUSIONS: The use of antiplatelet therapy lessened as platelet count decreased in patients with AIS with thrombocytopenia. However, our findings suggest that antiplatelet medications remain safe and effective for this population.

Structural Simplification of Podophyllotoxin: Discovery of γ-Butyrolactone Derivatives as Novel Antiviral Agents for Plant Protection.

Natural products are a valuable resource for the discovery of novel crop protection agents. A series of γ-butyrolactone derivatives, derived from the simplification of podophyllotoxin's structure, were synthesized and assessed for their efficacy against tobacco mosaic virus (TMV). Several derivatives exhibited notable antiviral properties, with compound 3g demonstrating the most potent in vivo anti-TMV activity. At 500 µg/mL, compound 3g achieved an inactivation effect of 87.8%, a protective effect of 71.7%, and a curative effect of 67.7%, surpassing the effectiveness of the commercial plant virucides ningnanmycin and ribavirin. Notably, the syn-diastereomer (syn-3g) exhibited superior antiviral activity compared to the anti-diastereomer (anti-3g). Mechanistic studies revealed that syn-3g could bind to the TMV coat protein and interfere with the self-assembly process of TMV particles. These findings indicate that compound 3g, with its simple chemical structure, could be a potential candidate for the development of novel antiviral agents for crop protection.

Intravenous thrombolysis versus dual antiplatelet therapy in minor ischemic stroke within the thrombolytic window (TAMIS): a multicenter cohort study.

Intravenous thrombolysis (IVT) and dual antiplatelet therapy (DAPT) have been widely used in minor ischemic stroke (MIS) treatment. However, the clinical outcomes and safety of these two treatments have not been compared within the early thrombolytic time window. Here, we conducted a multicenter, ambispective cohort study involving patients with MIS presenting within 4.5 h of symptom onset at 3 affiliated hospitals of Jinan University from 2018-2022. The patients were divided into the IVT group and DAPT group. The primary outcome was a 90-day excellent outcome (mRS ≤ 1). A total of 1,026 patients were enrolled, of whom 492 were assigned to the IVT group and 534 were assigned to the DAPT group. The IVT group had better 90-day excellent outcomes (mRS ≤ 1) than the DAPT group (OR 1.69, 95% CI 1.14-2.52, P = 0.010). Among the 623 patients with nondisabling stroke, the proportion of mRS ≤ 1 in the IVT group was higher than the DAPT group (P = 0.009). In the subtypes of MIS with large vessel occlusion/stenosis and with isolated symptoms, the 90-day outcomes of the IVT group and DAPT group were not different (P > 0.05). In conclusion, compared with DAPT, IVT was associated with better 90-day clinical outcomes in patients with MIS (in particular, for those with mRS > 1), including earlier clinical improvement.IVT also benefited the early neurological improvement of patients with severe stenosis/occlusion of intracranial large vessels, nondisabling mild stroke, nondisabling mild stroke with isolated symptoms.

Bone ingrowth induced by gelatin/chitosan internal matrix of 3DP Ti6Al4V scaffold.

Regarding its structural and mechanical adaptability to bone defects, 3D printed (3DP) Ti6Al4V scaffolds are widely used in orthopedics now, purposed to restore the function and mechanical stability of impaired bone. In scaffold fabrication, surface modification is acknowledged as a reliable strategy to enhance the interface interaction between 3DP Ti6Al4V scaffold and bone. Despite its advantage in bone-Ti6Al4V bonding improvement, surface modification lacks the ability to induce bone in-growth efficiently as expected. As an attempt to overcome this challenge, in the current work the inner voids of 3DP Ti6Al4V scaffold were occupied by a gelatin/chitosan porous matrix, purposed to act as a platform for guiding bone ingrowth. Firstly, the gelatin/chitosan matrix was prepared via freeze-drying using genipin as a crosslinker, resulting in a trabecular bone-like interconnected porous network characterized with a gelatin/chitosan ratio dependent swelling capability, degradation and model anti-bacterial drug release behavior. Besides of that, gelatin in the matrix was witnessed to accelerate biomineralization in simulated body fluid. Secondly, a formulated gelatin/chitosan matrix was embedded into 3DP Ti6Al4V scaffold to generate a composite scaffold capable of inducing bone in-growth. The followed studies showed gelatin/chitosan matrix can endow the scaffold with good biological and sustained drug release properties, along with minimal change to the compressive strength of the scaffold. The in vivo experiment results revealed that after 4 weeks of implantation, more new bone formation was witnessed in the inner structure of the composite scaffold than the 3DP Ti6Al4V scaffold, with the average bone volume fraction (BV/TV) value increased from 24.09 % to 46.08 %, the average trabecular bone thickness (Tb. Th) value increased from 0.118 mm to 0.278 mm. Therefore, it was confirmed an inner matrix in 3DP Ti6Al4V scaffold played an essential role in guiding bone in-growth.

Adolescent co-exposure to environmental cadmium and high-fat diet induces cognitive decline via Larp7 m6A-mediated SIRT6 inhibition.

The effects and underlying mechanisms of adolescent exposure to combined environmental hazards on cognitive function remain unclear. Here, using a combined exposure model, we found significant cognitive decline, hippocampal neuronal damage, and neuronal senescence in mice exposed to cadmium (Cd) and high-fat diet (HFD) during adolescence. Furthermore, we observed a significant downregulation of Sirtuin 6 (SIRT6) expression in the hippocampi of co-exposed mice. UBCS039, a specific SIRT6 activator, markedly reversed the above adverse effects. Further investigation revealed that co-exposure obviously reduced the levels of La ribonucleoprotein 7 (LARP7), disrupted the interaction between LARP7 and SIRT6, ultimately decreasing SIRT6 expression in mouse hippocampal neuronal cells. Overexpression of Larp7 reversed the combined exposure-induced SIRT6 decrease and senescence in mouse hippocampal neuronal cells. Additionally, the results showed notably elevated levels of Larp7 m6A and YTH domain family protein 2 (YTHDF2) in mouse hippocampal neuronal cells treated with the combined hazards. Ythdf2 short interfering RNA, RNA immunoprecipitation, and RNA stability assays further demonstrated that YTHDF2 mediated the degradation of Larp7 mRNA under combined exposure. Collectively, adolescent co-exposure to Cd and HFD causes hippocampal senescence and cognitive decline in mice by inhibiting LARP7-mediated SIRT6 expression in an m6A-dependent manner.

Factors influencing contractors' low-carbon construction behaviors in China: a LDA-DEMATEL-ISM approach.

Contractors' low-carbon construction behaviors (CLCB) are pivotal in advancing decarbonization during the construction phase. However, there exists a notable gap in the comprehensive exploration of the multifaceted factors and mechanisms influencing CLCB. Therefore, this study aims to systematically identify the factors influencing CLCB in China, examine the interrelationships among these factors, and pinpoint the key determinants. Based on topic modeling of Latent Dirichlet Allocation (LDA), influencing factors are identified firstly from the pertinent literature. Subsequently, the causality degree and centrality degree between these factors are assessed by the Decision-Making Trial and Evaluation Laboratory (DEMATEL), followed by the establishment of a hierarchical structure using the Interpretive Structural Modeling (ISM) method, culminating in the identification of pivotal factors. Findings reveal that (1) 21 influential factors influencing CLCB are identified. (2) "Incentive policies for relevant stakeholders" and "Low-carbon regulation and supervision" emerge as key influences. (3) CLCB should be guided by policy and subjective awareness, fortified by market and management support, underpinned by technology, and directly driven by economic considerations. This research furnishes valuable insights for promoting low-carbon development during the construction phase, thereby assisting the construction sector in achieving carbon peak and carbon neutrality.

High systemic inflammatory response index (SIRI) is an independent risk factor for poor outcome in IgA nephropathy patients.

BACKGROUND: The systemic inflammatory response index (SIRI), a straightforward and easily accessible measure of inflammation and prognosis, has drawn more attention lately. It is unknown, however, if SIRI is important for IgA nephropathy (IgAN) patients' outcomes. To better clarify these concerns, we conducted this investigation. METHOD: This retrospective study involved 981 patients with biopsy-confirmed IgAN from West China Hospital of Sichuan University between 2008 and 2019. The patients were divided into two groups based on the SIRI's optimal cut-off value calculated by the X-tile: the low SIRI group (SIRI ≤ 0.63, n = 312) and the high SIRI group (SIRI > 0.63, n = 669). Basic clinical characteristics at the time of renal biopsy were evaluated, and the relationship between SIRI and the combined endpoint was analyzed. We also used the Cox proportional hazard model and Kaplan‒Meier curve to evaluate the renal prognosis of IgAN. RESULTS: A total of 981 IgAN patients were included. During a median follow-up period of 56.7 months (36.8-80.4 months), 122 patients progressed to the combined endpoint (12.4%). Patients were divided into a low SIRI group (SIRI ≤ 0.63, n = 312) and a high SIRI group (SIRI > 0.63, n = 669) according to the optimal cut-off value of the systemic inflammatory response index (SIRI). Further analysis showed that a higher SIRI value was significantly associated with the risk of IgAN patients reaching the composite endpoint (HR 1.62, 95% CI 1.02-2.56, p = 0.041). CONCLUSION: High SIRI is a significant and independent risk factor for renal disease progression in IgAN patients.

Causal Relationship between Mitochondrial Biological Function and Periodontitis: Evidence from a Mendelian Randomization Study.

A growing number of studies indicate that mitochondrial dysfunction serves as a pathological mechanism for periodontitis. Therefore, this two-sample Mendelian randomization (MR) study was carried out to explore the causal associations between mitochondrial biological function and periodontitis, because the specific nature of this causal relationship remains inconclusive in existing MR studies. Inverse variance weighting, Mendelian randomization-Egger, weighted mode, simple mode, and weighted median analyses were performed to assess the causal relationships between the exposure factors and periodontitis. The results of the present study revealed a causal association between periodontitis and medium-chain specific acyl-CoA dehydrogenase (MCAD), malonyl-CoA decarboxylase (MLYCD), glutaredoxin 2 (Grx2), oligoribonuclease (ORN), and pyruvate carboxylase (PC). Notably, MCAD and MLYCD are causally linked to periodontitis, and serve as protective factors. However, Grx2, ORN, and PC function as risk factors for periodontitis. Our study established a causal relationship between mitochondrial biological function and periodontitis, and such insights may provide a promising approach for treating periodontitis via mitochondrial regulation.

The clinical and pathological evaluation of patients with immunoglobulin A nephropathy by diffusion tensor imaging and intravoxel incoherent motion diffusion-weighted imaging.

OBJECTIVES: To explore the efficacy of diffuse magnetic resonance imaging (MRI) for identifying clinicopathological changes in immunoglobulin A nephropathy (IgAN) patients. METHODS: The study enrolled IgAN patients and healthy volunteers. IgAN patients were divided into Group 1 [estimated glomerular filtration rate (eGFR) ≥ 90 mL/min/1.73 m2], Group 2 (60 ≤ eGFR < 90 mL/min/1.73 m2), and Group 3 (eGFR < 60 mL/min/1.73 m2). Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and diffusion tensor imaging (DTI) were performed via 3.0 T magnetic resonance. Diffuse MRI, clinical, and pathological indicators were collected and analysed. P < .05 was considered statistically significant. RESULTS: Forty-six IgAN patients and twenty-seven volunteers were enrolled. The apparent diffusion coefficient, diffusion coefficient (D), perfusion fraction (f), and fractional anisotropy (FA) were significantly different among IgAN subgroups and controls. These parameters were positively correlated with eGFR and negatively with creatinine, and inversely correlated with glomerular sclerosis, interstitial fibrosis, and tubular atrophy (all P < .05). They had significantly high area under the curve (AUC) for distinguishing IgAN patients from controls, while FA had the highest AUC in identifying Group 1 IgAN patients from volunteers. CONCLUSIONS: DTI and IVIM-DWI had the advantage of evaluating clinical and pathological changes in IgAN patients. DTI was superior at distinguishing early IgAN patients and might be a noninvasive marker for screening early IgAN patients from healthy individuals. ADVANCES IN KNOWLEDGE: DTI and IVIM-DWI could evaluate clinical and pathological changes and correlated with Oxford classification in IgAN patients. They could also identify IgAN patients from healthy populations, while DTI had superiority in differentiating early IgAN patients.

Total bilirubin level is associated with acute kidney injury in neonates admitted to the neonatal intensive care units: based on MIMIC-III database.

OBJECTIVE: The objective of this study was to investigate the association between total bilirubin and acute kidney injury (AKI) in neonates admitted to neonatal intensive care units (NICU). METHODS: All data utilized were extracted from Medical Information Mart for Intensive Care-III (MIMIC-III) in this retrospective cohort study. The primary outcome was the occurrence of AKI during hospitalization in the NICU, and the exposure was the initial measurement of total bilirubin levels within 24 h of neonatal admission to the NICU. The relationship between serum total bilirubin and AKI was evaluated by employing univariate and multivariate logistic regression models. Additionally, subgroup analyses were conducted based on birth weight, sepsis, and mechanical ventilation. RESULTS: This retrospective cohort study included a population of 1,726 neonates, and 95 neonates developed AKI. Total bilirubin, as a continuous variable, was linked with decreased AKI risk among neonates admitted to the NICU [odds ratio (OR) = 0.77, 95% confidence interval (CI): 0.64-0.92]. Similarly, when total bilirubin levels were categorized by tertiles, tertiles 3 showed a significant association with decreased AKI risk (OR = 0.39, 95%CI: 0.19-0.83). The relationship of total bilirubin level and AKI was also existent among neonates admitted to the NICU who were underweight, had not sepsis, and received mechanical ventilation. CONCLUSION: Total bilirubin level may be a protective factor for the risk of developing AKI.

Fundamental Aspects of Phase-Separated Biomolecular Condensates.

Biomolecular condensates, formed through phase separation, are upending our understanding in much of molecular, cell, and developmental biology. There is an urgent need to elucidate the physicochemical foundations of the behaviors and properties of biomolecular condensates. Here we aim to fill this need by writing a comprehensive, critical, and accessible review on the fundamental aspects of phase-separated biomolecular condensates. We introduce the relevant theoretical background, present the theoretical basis for the computation and experimental measurement of condensate properties, and give mechanistic interpretations of condensate behaviors and properties in terms of interactions at the molecular and residue levels.

Tannic acid and silicate-functionalized polyvinyl alcohol-hyaluronic acid hydrogel for infected diabetic wound healing.

Healing of chronic diabetic wounds is challenging due to complications of severe inflammatory microenvironment, bacterial infection and poor vascular formation. Herein, a novel injectable polyvinyl alcohol-hyaluronic acid-based composite hydrogel was developed, with tannic acid (TA) and silicate functionalization to fabricate an 'all-in-one' hydrogel PTKH. On one hand, after being locally injected into the wound site, the hydrogel underwent a gradual sol-gel transition in situ, forming an adhesive and protective dressing for the wound. Manipulations of rheological characteristics, mechanical properties and swelling ability of PTKH could be performed via regulating TA and silicate content in hydrogel. On the other hand, PTKH was capable of eliminating reactive oxygen species overexpression, combating infection and generating a cell-favored microenvironment for wound healing acceleration in vitro. Subsequent animal studies demonstrated that PTKH could greatly stimulate angiogenesis and epithelization, accompanied with inflammation and infection risk reduction. Therefore, in consideration of its impressive in vitro and in vivo outcomes, this 'all-in-one' multifunctional hydrogel may hold promise for chronic diabetic wound treatment.