Microenvironment-responsive nanosystems for ischemic stroke therapy.

Ischemic stroke, a common neurological disorder caused by impaired blood supply to the brain, presents a therapeutic challenge. Conventional treatments like thrombolysis and neuroprotection drugs lack ideal drug delivery systems, limiting their effectiveness. Selectively delivering therapies to the ischemic cerebral tissue holds great potential for preventing and/or treating ischemia-related pathological symptoms. The unique pathological microenvironment of the brain after ischemic stroke, characterized by hypoxia, acidity, and inflammation, offers new possibilities for targeted drug delivery. Pathological microenvironment-responsive nanosystems, extensively investigated in tumors with hypoxia-responsive systems as an example, could also respond to the ischemic cerebral microenvironment and achieve brain-targeted drug delivery and release. These emerging nanosystems are gaining traction for ischemic stroke treatment. In this review, we expound on the cerebral pathological microenvironment and clinical treatment strategies of ischemic stroke, highlight various stimulus-responsive materials employed in constructing ischemic stroke microenvironment-responsive nano delivery systems, and discuss the application of these microenvironment-responsive nanosystems in microenvironment regulation for ischemic stroke treatment.

Co-treatment of agri-food waste streams using black soldier fly larvae (Hermetia illucens L.): A sustainable solution for rural waste management.

The management of rural waste, particularly agri-food waste, poses a major challenge to the ecosystem health. This study investigated the efficacy of black soldier fly larvae (Hermetia illucens L., BSFL) bioconversion for agri-food waste under independent treatment or co-treatment strategies using chicken manure and food waste as a model system. The results showed a synergistic effect of co-treating agri-food waste from different sources. The co-treatment strategy enhanced bioconversion efficiency, resulting in a 1.31-fold waste reduction rate and a 1.93-fold bioconversion rate. Additionally, larval growth performance and biomass quality of BSFL were improved, while lauric acid and oleic acid were enriched in the larval fat from the co-treatment strategy. 16S rRNA amplicon sequencing revealed that the co-treatment strategy reshaped both the residue and larval gut microbiota, with distinct enrichment of taxonomical biomarkers. Furthermore, under this strategy, metabolic functions of the residue microbiota were significantly activated, especially carbohydrate, amino acid, and lipid metabolism were enhanced by 16.3%, 23.5%, and 20.2%, respectively. The early colonization of lactic acid bacteria (Weisella and Aerococcus) in the residue, coupled with a symbiotic relationship between Enterococcus in the larval gut and the host, likely promoted organic matter degradation and larval growth performance. Scaling up the findings to a national level in China suggests that the co-treatment strategy can increase waste reduction quantity by 86,329 tonnes annually and produce more larval protein and fat with a market value of approximately US$237 million. Therefore, co-treatment of agri-food waste streams using BSFL presents a sustainable solution for rural waste management that potentially contributes to the achievement of SDG2 (Zero Hunger), SDG3 (Good Health and Well-Being), and SDG12 (Responsible Consumption and Production).

Numerical study on heat transfer and pressure performance of different suspension nozzles.

The drying process of the lithium battery pole pieces makes extensive use of the suspension nozzle. It is of great significance to study the heat transfer and pressure steady-state characteristics of the suspension nozzle and to select the appropriate nozzle structure for the production of pole pieces. Based on the SST k - ω turbulence model, this article numerically simulates the impact jet process of suspension nozzles with slits, injection holes, and effusion holes. There is a qualitative and quantitative analysis of the distribution of their velocity field, temperature field, local Nusselt number, average Nusselt number, local pressure coefficient, and average pressure coefficient, and the comprehensive performance index of the nozzle is proposed. The results show that when the weight factor of heat transfer performance α is less than 21.61% and the weight factor of pressure performance ß is more than 78.39%, the comprehensive performance of the traditional suspension nozzle with double slits is the best. As the α is increasing, the ß is decreasing. The comprehensive performance of the suspension nozzle with effusion holes is the best. The turbulent intermittence, interaction between neighbouring jets, and edge effects affect the heat transfer and pressure uniformity of the suspension nozzle.

Classification of Laboratory Test Outcomes for Maintenance Hemodialysis Patients Using Cellular Bioelectrical Measurements.

Background: End-stage kidney disease (ESKD) patients often face complications like anemia, malnutrition, and cardiovascular issues. Serological tests, which are uncomfortable and not frequently conducted, assist in medical assessments. A non-invasive, convenient method for determining these test results would be beneficial for monitoring patient health. Objective: This study develops machine learning models to estimate key serological test results using non-invasive cellular bioelectrical impedance measurements, a routine procedure for ESKD patients. Methods: The study employs two machine learning models, Support Vector Machine (SVM) and Random Forest (RF), to determine key serological tests by classifying cell bioelectrical indicators. Data from 688 patients, comprising 3,872 biochemical-bioelectrical records, were used for model validation. Results: Both SVM and RF models effectively categorized key serological results (albumin, phosphorus, parathyroid hormone) into low, normal, and high. RF generally outperformed SVM, except in classifying calcium levels in women. Conclusion: The machine learning models effectively classified serological test results for maintenance hemodialysis patients using cellular bioelectrical indicators, therefore can help in making judgments about physicochemical indicators using electrical signals, thereby reducing the frequency of serological tests.

Approved drugs and natural products at clinical stages for treating Alzheimer's disease.

Alzheimer's disease (AD) remains the foremost cause of dementia and represents a significant unmet healthcare need globally. The complex pathogenesis of AD, characterized by various pathological and physiological events, has historically challenged the development of anti-AD drugs. However, recent breakthroughs in AD drug development, including the approvals of aducanumab, lecanemab, and sodium oligomannate (GV-971), have ended a nearly two-decade hiatus in the introduction of new AD drugs. These developments have addressed long-standing challenges in AD drug development, marking a substantial shift in the therapeutic landscape of AD. Moreover, natural products (NPs) have shown promise in AD drug research, with several currently under clinical investigation. Their distinct properties and mechanisms of action offer new avenues to complement and enhance existing AD treatment approaches. This review article aims to provide an overview of the recent advancements and prospects in AD therapeutics, focusing on both NPs and approved drugs.

The impact of social media information exposure on appearance anxiety in young acne patients: a moderated chain mediation model.

Introduction: The boom of social media has provided a wider space for ordinary people to display themselves, but visual presentation has also intensified the focus on appearance, which in turn triggers anxiety about appearance. The study aims to investigate the impact of social media information exposure on appearance anxiety in young acne patients and the pathways and mechanisms that cause this effect. Methods: A moderated chain mediation model was constructed, and a questionnaire was used to collect information on social media information exposure, internalization of beauty ideals, fear of negative evaluation, self-esteem, and appearance anxiety in young acne patients (N = 382), and the relationships between the variables were explored through regression analysis. Results: The results show that there was a significant path of effect (t > 2.5, p < 0.05) between social media information exposure, internalization of beauty ideals, fear of negative evaluation, and appearance anxiety. Self-esteem significantly moderated the relationship between social media information exposure and internalization of beauty ideals (t < -2, p < 0.05). Discussion: In conclusion, in young acne patients, internalization of beauty ideals and fear of negative evaluation chain mediated the association between social media information exposure and appearance anxiety, and young acne patients' internalization of beauty ideals was inversely correlated with their level of self-esteem.

Impact of corrupt admission on the mental health of Chinese adolescents.

Through preferential treatment by education officials or through bribery, some adolescents can obtain admission to a junior high school. However, it is unclear whether it affects the mental health of adolescents. This study used Propensity Score Matching to examine the effects of corruption on adolescent mental health. A total of 17,254 junior high school students sample (11-18 years old; 48.7% girls and 53.1% boys) were used from the China Education Panel Survey. 14.1% of adolescents attended a junior high school by corrupt means, corruption had a significantly negative effect on the mental health of these adolescents (ATT = -0.388, p < 0.01), the reasons grounded in the fact that they received more criticisms from teachers and wanted to leave their current school. In general, corruption in the admissions process can have detrimental effects on the mental health of adolescents. This study extends the previous articles on how to improve adolescent mental health and complements the application of cognitive dissonance theory. Findings from this study revealed that anti-corruption in the education sector is necessary, and the institutional design to ensure fair enrolment in basic education will contribute to the mental health of adolescents.

Study on heat transfer and pressure steady-state characteristics of a floating nozzle under a moving wall.

This work considers the flow field as two-dimensional turbulent flow and studies the steady-state properties of heat transfer and the pressure of the suspension nozzle. An adiabatic wall parallel to the moving wall and two slit entrances at either end of the adiabatic wall make up the rectangular flow field. The SST k - ω turbulence model is used in the turbulence computation. Both qualitative and quantitative analyses are conducted on the distribution of the flow field, temperature field, local Nusselt number, local pressure coefficient, average Nusselt number, and average pressure coefficient under various combination conditions. The findings indicate that when the suspension nozzle's flow field varies greatly, wall-jet velocity ratio is 0.1. A rise in Jet inclination angle is not helpful for the wall's suspension, and it has minimal effect on the flow field. The flow field is greatly influenced by separation space-slit width ratio. Larger separation space-slit width ratio values are advantageous for the wall's heat transmission but unfavorable for the wall's suspension. The flow field is most influenced by wall-jet velocity ratio. The wall's ability to convey heat is stronger the higher the wall-jet velocity ratio, but its ability to support weight falls.

Rational or altruistic: the impact of social media information exposure on Chinese youth's willingness to donate blood.

Background: Non-remunerated blood donation is the main approach for various medical institutions to get the source of blood supply, but the blood supply shortage is still a problem in today's society. Social media has become the main approach of information acquisition for youth groups nowadays, and the information on social media will have an impact on people's behavioral decisions. The objective of this study was therefore to investigate the correlation between social media exposure to relevant information about blood donation and the willingness of youths to donate blood. Methods: We collected data from 455 questionnaires through an online questionnaire and structural equation modeling was constructed for validation. Data were analyzed for reliability, validity, and demographic differences using IBM-SPSS 26.0, and IBM-SPSS-AMOS 26.0 was used for model fit analysis and path analysis. Results: The results of the study showed that there was a positive correlation between social media exposure to relevant blood donation information and willingness to donate blood (ß = 0.262, p < 0.001), altruism (ß = 0.203, p < 0.001) and self-efficacy (ß = 0.170, p < 0.001). While there was also a positive correlation between attitude toward blood donation and self-efficacy (ß = 0.560, p < 0.001), there was no positive correlation between it and willingness to donate blood (ß = -0.180, p = 0.786). There was also a positive correlation between altruism and willingness to donate blood (ß = 0.150, p < 0.05) and attitude toward blood donation (ß = 0.150, p < 0.001). Similarly, there was a positive correlation between self-efficacy and willingness to donate blood (ß = 0.371, p < 0.001). Conclusion: Exposure to more information related to blood donation on social media can increase the willingness of the youth population to donate blood, while exposure to information related to altruism and self-efficacy on social media can also enhance young people's attitudes toward blood donation, while further strengthening their willingness to donate.

Predictive value of the domain specific PLA2R antibodies for clinical remission in patients with primary membranous nephropathy: A retrospective study.

BACKGROUND: M-type phospholipase A2 receptor (PLA2R) is a major auto-antigen of primary membranous nephropathy(PMN). Anti-PLA2R antibody levels are closely associated with disease severity and therapeutic effectiveness. Analysis of PLA2R antigen epitope reactivity may have a greater predictive value for remission compared with total PLA2R-antibody level. This study aims to elucidate the relationship between domain-specific antibody levels and clinical outcomes of PMN. METHODS: This retrospective analysis included 87 patients with PLA2R-associated PMN. Among them, 40 and 47 were treated with rituximab (RTX) and cyclophosphamide (CTX) regimen, respectively. The quantitative detection of -immunoglobulin G (IgG)/-IgG4 targeting PLA2R and its epitope levels in the serum of patients with PMN were obtained through time-resolved fluorescence immunoassays and served as biomarkers in evaluating the treatment effectiveness. A predictive PMN remission possibility nomogram was developed using multivariate logistic regression analysis. Discrimination in the prediction model was assessed using the area under the receiver operating characteristic curve (AUC-ROC).Bootstrap ROC was used to evaluate the performance of the prediction model. RESULTS: After a 6-month treatment period, the remission rates of proteinuria, including complete remission and partial remission in the RTX and CTX groups, were 70% and 70.21% (P = 0.983), respectively. However, there was a significant difference in immunological remission in the PLA2R-IgG4 between the RTX and CTX groups (21.43% vs. 61.90%, P = 0.019). Furthermore, we found differences in PLA2R-CysR-IgG4(P = 0.030), PLA2R-CTLD1-IgG4(P = 0.005), PLA2R-CTLD678-IgG4(P = 0.003), and epitope spreading (P = 0.023) between responders and non-responders in the CTX group. Multivariate logistic analysis showed that higher levels of urinary protein (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.26-0.95; P = 0.035) and higher levels of PLA2R-CTLD1-IgG4 (OR, 0.79; 95%CI,0.62-0.99; P = 0.041) were independent risk factors for early remission. A multivariate model for estimating the possibility of early remission in patients with PMN is presented as a nomogram. The AUC-ROC of our model was 0.721 (95%CI, 0.601-0.840), in consistency with the results obtained with internal validation, for which the AUC-ROC was 0.711 (95%CI, 0.587-0.824), thus, demonstrating robustness. CONCLUSIONS: Cyclophosphamide can induce immunological remission earlier than rituximab at the span of 6 months. The PLA2R-CTLD1-IgG4 has a better predict value than total PLA2R-IgG for remission of proteinuria at the 6th month.

Shared genetic factors and causal association between chronic hepatitis C infection and diffuse large B cell lymphoma.

BACKGROUND: Epidemiological research and systematic meta-analyses indicate a higher risk of B-cell lymphomas in patients with chronic hepatitis C virus (HCV) compared to non-infected individuals. However, the genetic links between HCV and these lymphomas remain under-researched. METHODS: Mendelian randomization analysis was employed to explore the association between chronic hepatitis C (CHC) and B-cell lymphomas as well as chronic lymphocytic leukemia (CLL). Approximate Bayes Factor (ABF) localization analysis was conducted to find shared genetic variants that might connect CHC with B-cell lymphomas and chronic lymphocytic leukemia (CLL). Furthermore, The Variant Effect Predictor (VEP) was utilized to annotate the functional effects of the identified genetic variants. RESULTS: Mendelian randomization revealed a significant association between CHC and increased diffuse large B cell lymphoma (DLBCL) risk (OR: 1.34; 95% CI: 1.01-1.78; P = 0.0397). Subsequent colocalization analysis pinpointed two noteworthy variants, rs17208853 (chr6:32408583) and rs482759 (chr6:32227240) between these two traits. The annotation of these variants through the VEP revealed their respective associations with the butyrophilin-like protein 2 (BTNL2) and notch receptor 4 (NOTCH4) genes, along with the long non-coding RNA (lncRNA) TSBP1-AS1. CONCLUSION: This research provides a refined genetic understanding of the CHC-DLBCL connection, opening avenues for targeted therapeutic research and intervention.

FLAMES overlaying anti-N-methyl-D-aspartate receptor encephalitis: a case report and literature review.

BACKGROUND: In recent years, simultaneous or sequential occurrence of MOG antibody disease and anti-NMDAR encephalitis in the same patient has been reported with increasing frequency. Scholars refer to the overlapping occurrence of these two disorders as MOG antibody disease and anti-NMDAR encephalitis overlap syndrome (MNOS). Cortical T2-weighted fluid-attenuated inversion recovery (FLAIR) -hyperintense lesions in anti-MOG-associated encephalitis with seizures (FLAMES) is a rare clinical phenotype of MOGAD in which cortical FLAIR high-signal lesions are unilateral, with little spread to the cortex and meninges bilaterally. Although cases of FLAMES have been consistently reported. However, to our knowledge, such cases of FLAMES combined with NMDARE are rare. CASE PRESENTATION: Here, we describe a case of FLAMES combined with anti-NMDARE. The patient was a young male, 29 years old, admitted to our hospital with isolated seizures, whose MRI showed unilateral thalamic and bilateral frontal and parietal leptomeningeal involvement. Since we were unaware of the possibility of bilateral meningo-cortical MOGAD manifestations, the case was initially diagnosed as viral encephalitis and was given antiviral therapy. The diagnosis was not clarified until anti-NMDAR-IgG and MOG-IgG positivity was detected in the cerebrospinal fluid and serum. The patient was then treated with high-dose corticosteroids and his symptoms responded well to the steroids. Therefore, this case expands the clinical spectrum of MNOS overlap syndrome. In addition, we describe the clinical features of MNOS by summarizing the existing literature and exploring the possible mechanisms of its immune response. CONCLUSIONS: Our case serves as a reminder to clinicians that when patients present with atypical clinical manifestations such as seizures, consideration should be given to MNOS and conduct testing for various relevant autoantibodies (including MOG abs) and viruses in both serum and cerebrospinal fluid, as it is easy to misdiagnose the disease as other CNS diseases, such as viral meningoencephalitis. This syndrome exhibits a high responsiveness to steroids, highlighting the critical importance of recognizing the clinical and neuroimaging features of this overlap syndrome for prompt diagnosis and treatment. Furthermore, it enriches the disease spectrum of MNOS.

Long-term dynamic changes and influencing factors of corneal morphology after multiple intravitreal injections of anti-VEGF drugs.

To observe alterations in corneal morphology caused by repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF). Prospective cohort study. Seventy-seven eyes were treated with intravitreal injection of anti-VEGF from June 2021 to March 2023. There were 25 eyes of neovascular age-related macular degeneration (nAMD), 24 eyes of diabetic macular edema (DME), and 28 eyes of retinal vein occlusion (RVO). Aflibercept was used in 37 eyes and Ranibizumab was used in 40 eyes. 3 + PRN was used. Corneal endothelium and corneal thickness were measured using a corneal endothelial microscope. The data related to central corneal thickness, corneal endothelial cell density (ECD), average cell size, coefficient of variation (CV), proportion of hexagonal cells (Hex%) was collected. A comparison was also made between baseline and the dynamic changes of all indexes 1 year following the last injection. It was observed that in comparison to baseline, ECD and Hex% decreased significantly after the 3rd injection of Aflibercept and Ranibizumab. However, ECD did not decrease further and remained at the same level as after the last injection. Hex% and average cell size increased to a certain extent in comparison to the last injection. All the changes were found to be statistically significant (P < .01). After 3 injections, ECD in DME group was markedly lower than that in nAMD and RVO group, but the CV in DME group was higher than that in nAMD as well as RVO groups, and all the differences were statistically significant (P < .05). Following intravitreal anti-VEGF therapy, DME is more likely than other disorders to result in a decrease in ECD. Repeated intravitreal injections of anti-VEGF drugs can reduce the Hex% and ECD to a certain extent. After the last injection, Hex% can progressively recover, and ECD can remain stable without further declining. After injections, ECD in DME group was found to be significantly lower than that in nAMD and RVO groups, but CV in DME group was significantly higher in comparison to the other 2 groups. In patients with macular edema, repeated intravitreal injections of anti-VEGF may have certain effects on corneal morphology. Patients with diabetes mellitus in particular should pay special attention to corneal safety following repeated intravitreal injections if they have significantly reduced ECD at baseline.

Black soldier fly larvae mitigate greenhouse gas emissions from domestic biodegradable waste by recycling carbon and nitrogen and reconstructing microbial communities.

Black soldier fly larvae have been proven to reduce greenhouse gas emissions in the treatment of organic waste. However, the microbial mechanisms involved have not been fully understood. The current study mainly examined the dynamic changes of carbon and nitrogen, greenhouse gas emissions, the succession of microbial community structure, and changes in functional gene abundance in organic waste under larvae treatment and non-aeration composting. Thirty percent carbon and 55% nitrogen in the organic waste supplied were stored in larvae biomass. Compared to the non-aeration composting, the larvae bioreactor reduced the proportion of carbon and nitrogen converted into greenhouse gases (CO2, CH4, and N2O decreased by 62%, 87%, and 95%, respectively). 16S rRNA sequencing analysis indicated that the larvae bioreactor increased the relative abundance of Methanophaga, Marinobacter, and Campylobacter during the bioprocess, enhancing the consumption of CH4 and N2O. The metagenomic data showed that the intervention of larvae reduced the ratio of (nirK + nirS + nor)/nosZ in the residues, thereby reducing the emission of N2O. Larvae also increased the functional gene abundance of nirA, nirB, nirD, and nrfA in the residues, making nitrite more inclined to be reduced to ammonia instead of N2O. The larvae bioreactor mitigated greenhouse gas emissions by redistributing carbon and nitrogen and remodeling microbiomes during waste bioconversion, giving related enterprises a relative advantage in carbon trading.

Brain-wide neuronal circuit connectome of human glioblastoma.

Glioblastoma (GBM), a universally fatal brain cancer, infiltrates the brain and can be synaptically innervated by neurons, which drives tumor progression 1-6 . Synaptic inputs onto GBM cells identified so far are largely short-range and glutamatergic 7-9 . The extent of integration of GBM cells into brain-wide neuronal circuitry is not well understood. Here we applied a rabies virus-mediated retrograde monosynaptic tracing approach 10-12 to systematically investigate circuit integration of human GBM organoids transplanted into adult mice. We found that GBM cells from multiple patients rapidly integrated into brain-wide neuronal circuits and exhibited diverse local and long-range connectivity. Beyond glutamatergic inputs, we identified a variety of neuromodulatory inputs across the brain, including cholinergic inputs from the basal forebrain. Acute acetylcholine stimulation induced sustained calcium oscillations and long-lasting transcriptional reprogramming of GBM cells into a more invasive state via the metabotropic CHRM3 receptor. CHRM3 downregulation suppressed GBM cell invasion, proliferation, and survival in vitro and in vivo. Together, these results reveal the capacity of human GBM cells to rapidly and robustly integrate into anatomically and molecularly diverse neuronal circuitry in the adult brain and support a model wherein rapid synapse formation onto GBM cells and transient activation of upstream neurons may lead to a long-lasting increase in fitness to promote tumor infiltration and progression.

Camelliazijinica (Theaceae), a new species endemic to Danxia landscape from Guangdong Province, China.

A new species of the genus Camellia (Theaceae), Camelliazijinica, discovered in the Danxia landscape from Guangdong Province, China, is characterized and illustrated. Phylogenetic analysis based on chloroplast genomes suggested its affinity with C.drupifera, C.oleifera and C.fluviatilis, however, it morphologically differs from all of the latter by leaf shape and size. Phonologically, it most closely resembles C.microphylla, but can be distinguished from the latter by its young branchlets glabrous (vs. densely pubescent), fewer bracteoles and sepals, diverse leaf shape, midvein raised slightly with sparsely pubescent or glabrous (vs. prominently with densely pubescent) and leaf adaxially matt (vs. vernicose) when dried. By morphological and molecular analyses, Camelliazijinica represented a distinct new species of C.sect.Paracamellia.

Study on nonlinear dynamic characteristics of a two-speed transmission system at low speed.

A pure shear mechanical model of low gear of six-degree-of-freedom two-speed transmission system is established by using lumped parameter method. The Runge-Kutta method is used to numerically solve the aforementioned nonlinear system. The variation of transmission error between gears is analyzed by using global bifurcation, time domain diagram, phase diagram and Poincare cross section. Moreover, the transfer error bifurcation characteristics of the solar wheel and the first planetary wheel under different gear moduli are investigated. The results show that: by taking the excitation frequency as the control parameter, the system includes period-1 motion, period-2 motion, quasi-periodic motion, multiperiodic motion, and chaotic motion. With the increase of gear modulus, the system mainly presents chaotic motion in the medium frequency range (0.5<ωh≤2). It shows stable period-1 motion in the high frequency range (2<ωh≤3), and the higher the modulus, the wider the high frequency range of period-1 motion. The research results can provide reference for the design and optimization of this kind of two-speed transmission system in the future.

Antiviral effectiveness and survival correlation of azvudine and nirmatrelvir/ritonavir in elderly severe patients with COVID-19: a retrospective real-world study.

Background: Azvudine and nirmatrelvir/ritonavir are approved to treat mild-to-moderate coronavirus disease 2019 (COVID-19) in adults with a high risk for progression to severe infection. We sought to compare the antiviral effectiveness and clinical outcomes of elderly severe patients with COVID-19 receiving these two antiviral agents. Methods: In this observational study, we identified 249 elderly patients with severe COVID-19 infection who were admitted to the Second Medical Center of the People's Liberation Army General Hospital from December 2022 to January 2023, including 128 azvudine recipients, 66 nirmatrelvir/ritonavir recipients and 55 patients not received antiviral treatments. We compared the cycle threshold (Ct) value dynamic change of all three groups. The primary outcome was a composite outcome of disease progression, including all-cause death, intensive care unit admission, and initiation of invasive mechanical ventilation. The outcomes of all enrolled patients were followed up from the electronic medical record system. Kaplan-Meier and Cox risk proportional regression analyses were used to compare the clinical outcomes of all three groups. To more directly compare the effectiveness of the two antiviral drugs, we performed propensity-score matching between the two antiviral groups and compared antiviral efficacy and clinical outcomes in the matched population. Findings: Among 249 patients (mean age, 91.41 years), 77 patients died during the follow-up period. When compared to patients who did not receive any antivirals, neither nirmatrelvir/ritonavir nor azvudine demonstrated a survival benefit. The Cox analysis of the all-cause death of the three groups showed that the risk of death was 0.730 (0.423-1.262) in the azvudine group 0.802 (0.435-1.480) and in the nirmatrelvir/ritonavir group compared with the non-antiviral group. After propensity score matching, we included 58 azvudine recipients and 58 nirmatrelvir/ritonavir recipients. The fitted curve of the Ct value after matching illustrated that the rate of viral decline in the early stage of nirmatrelvir/ritonavir treatment seems to surpass that of azvudine, but there was no statistical significance. Azvudine was seemly associated with a lower risk of composite outcomes (HR:1.676, 95% CI:0.805-3.488) and short-term all-cause death (HR: 1.291, 95%CI: 0.546-3.051). Interpretation: Patients who received azvudine have a similar antiviral effectiveness and survival curve trend compared to nirmatrelvir/ritonavir. In this limited series, antiviral treatment was not associated with a significant clinical benefit. This lack of clinical benefit might be attributed to potential bias. Funding: This study was supported by the "National Key R&D Program of China" (Funding No. 2020YFC2008900) and the National Defense Science and Technology Innovation Special Zone Project (223-CXCY-N101-07-18-01).

Sustainable and Rapid Water Purification at the Confined Hydrogel Interface.

Emerging organic contaminants in water matrices have challenged ecosystems and human health safety. Persulfate-based advanced oxidation processes (PS-AOPs) have attracted much attention as they address potential water purification challenges. However, overcoming the mass transfer constraint and the catalyst's inherent site agglomeration in the heterogeneous system remains urgent. Herein, the abundant metal-anchored loading (≈6-8 g m-2) of alginate hydrogel membranes coupled with cross-flow mode as an efficient strategy for water purification applications is proposed. The organic flux of the confined hydrogel interfaces sharply enlarges with the reduction of the thickness of the boundary layer via the pressure field. The normalized property of the system displays a remarkable organic (sulfonamides) elimination rate of 4.87 × 104 mg min-1 mol-1. Furthermore, due to the fast reaction time (<1 min), cross-flow mode only reaches a meager energy cost (≈2.21 Wh m-3) under the pressure drive field. It is anticipated that this finding provides insight into the novel design with ultrafast organic removal performance and low techno-economic cost (i.e., energy operation cost, material, and reagent cost) for the field of water purification under various PS-AOPs challenging scenarios.

Fructus lycii oligosaccharide alleviates acute liver injury via PI3K/Akt/mTOR pathway.

Regulating the immune-environment is essential for treating acute liver injury (ALI). However, the deficiency of an effective immune balancer restricted progress. Herein, we reported an oligosaccharide from Fructus lycii oligosaccharide (FLO). To investigate the effects of FLO, we adopted primary macrophages and LO2 for experiments in vitro. In vivo, we assessed the influence of FLO in ALI with histochemical staining and enzyme indicators detection. Following that, we clarified the underlying mechanisms using western blotting and immunofluorescence. Our results indicated that FLO (100 µg/mL) showed apparent inflammatory reversal effects by shifting the phenotype of macrophages from M1 to M2 without causing any cytotoxicity. Furthermore, CCl4-induced mice were significantly improved by FLO intragastric administration. Meanwhile, PI3K/AKT/mTOR pathway was confirmed for the up-regulation of IL-10 via M2 polarization of macrophages. Collectively, our findings highlight the beneficial effects of FLO on ALI therapy via M1 to M2 macrophage conversion.