FoxO1-modulated macrophage polarization regulates osteogenesis via PPAR-γ signaling.

Periodontitis, a common chronic inflammatory disease, epitomizes a significant impairment in the host immune system and an imbalance of bone metabolism. Macrophage polarization, a dynamic process dictated by the microenvironment, intricately contributes to the interplay between the immune system and bone remodeling, namely the osteoimmune system. Forkhead box protein O1 (FoxO1) has been shown to play a dramatic role in mediating oxidative stress, bone mass, as well as cellular metabolism. Nevertheless, the function and underlying mechanisms of FoxO1 in regulating macrophage polarization-mediated osteogenesis in periodontitis remain to be further elucidated. Here, we found that FoxO1 expression was closely linked to periodontitis, accompanied by aggravated inflammation. Notably, FoxO1 knockdown skewed macrophage polarization from M1 to the antiinflammatory M2 phenotype under inflammatory conditions, which rescued the impaired osteogenic potential. Mechanistically, we revealed that the enhancement of the transcription of peroxisome proliferator-activated receptor (PPAR) signaling in FoxO1-knockdown macrophages. In agreement with this contention, GW9662, a specific inhibitor of PPAR-γ signaling, greatly aggravated macrophage polarization from M2 to the M1 phenotype and attenuated osteogenic potential under inflammatory conditions. Additionally, PPAR-γ signaling agonist rosiglitazone (RSG) was applied to address ligature-induced periodontitis with attenuated inflammation. Our data lend conceptual credence to the function of FoxO1 in mediating macrophage polarization-regulated osteogenesis which serves as a novel therapeutic target for periodontitis.

Silver coordination-induced n-doping of PCBM for stable and efficient inverted perovskite solar cells.

The bidirectional migration of halides and silver causes irreversible chemical corrosion to the electrodes and perovskite layer, affecting long-term operation stability of perovskite solar cells. Here we propose a silver coordination-induced n-doping of [6,6]-phenyl-C61-butyric acid methyl ester strategy to safeguard Ag electrode against corrosion and impede the migration of iodine within the PSCs. Meanwhile, the coordination between DCBP and silver induces n-doping in the PCBM layer, accelerating electron extraction from the perovskite layer. The resultant PSCs demonstrate an efficiency of 26.03% (certified 25.51%) with a minimal non-radiative voltage loss of 126 mV. The PCE of resulting devices retain 95% of their initial value after 2500 h of continuous maximum power point tracking under one-sun irradiation, and > 90% of their initial value even after 1500 h of accelerated aging at 85 °C and 85% relative humidity.

Development of active film based on collagen and hydroxypropyl methylcellulose incorporating apple polyphenol for food packaging.

Collagen (COL)-hydroxypropyl methylcellulose (HPMC) blended films with apple polyphenol (AP) as cross-linking agent and antioxidant compound were developed to produce biodegradable active packaging film. The effects of AP content on the rheological behavior of the blended solution, the structure, physicochemical and functional properties of the blended film were systematically investigated. The incorporation of AP increased the viscosity and reduced the fluidity of COL-HPMC solution. The results of rheological tests and FTIR analysis manifested the formation of hydrogen bonding interactions between collagen, HPMC and AP, which made the structures of COL-HP-AP films more compact. The mechanical strength, UV-blocking ability, water-resistance performance and thermostability were gradually enhanced as increasing AP content. DPPH free radical scavenging experiment showed that a small amount of AP could efficiently improve the antioxidant activity of COL-HP film, and with increasing AP content to 5 wt%, the scavenging rate was as high as 94.23 %. Active film containing 5 wt% AP showed obvious antibacterial effect on E. coli and S. aureus, and it could effectively prevent the oxidation of vitamin C and reduce the accumulation of MDA on green pepper during the storage. COL-HP-AP films have great potential in food packaging field for extending the shelf life of food.

Monomeric C-reactive protein is associated with severity and prognosis of decompensated hepatitis B cirrhosis.

C-reactive protein (CRP) is an acute-phase protein produced by the liver in response to infection and during chronic inflammatory disorders. Systemic inflammation is a major driver of cirrhosis progression from the compensated to the decompensated stage. Previous studies have shown that pentameric CRP (pCRP) to be a weak predictor of disease severity and prognosis in patients with decompensated hepatitis B cirrhosis, with it being only helpful for identifying patients with a higher short-term risk of death under certain conditions. Accumulating evidence indicates that pCRP dissociates to and acts primarily as the monomeric conformation (mCRP) at inflammatory loci, suggesting that mCRP may be a potentially superior disease marker with higher specificity and relevance to pathogenesis. However, it is unknown whether mCRP and anti-mCRP autoantibodies are associated with disease severity, or progression in decompensated hepatitis B cirrhosis. In this study, we evaluated the serum levels of mCRP and anti-mCRP autoantibodies in patients with decompensated cirrhosis of hepatitis B and their association with disease severity and theoretical prognosis. The results showed that patients with high mCRP and anti-mCRP autoantibody levels had more severe liver damage and that coagulation function was worse in patients with high anti-mCRP autoantibodies. Analysis of the correlation between pCRP, mCRP and anti-mCRP autoantibody levels with Model for End-Stage Liver Disease (MELD), Albumin-Bilirubin (ALBI), and Child-Turcotte-Pugh (CTP) prognostic scores showed that mCRP was the most strongly correlated with MELD score, followed by anti-mCRP autoantibodies; conversely, pCRP was not significantly correlated with prognostic score. Therefore, mCRP and anti-mCRP autoantibodies may be more advantageous clinical indicators than pCRP for evaluating the pathological state of decompensated hepatitis B cirrhosis.

Improvement of social functioning in patients with first-episode schizophrenia using blonanserin treatment: a prospective, multi-centre, single-arm clinical trial.

Objectives: This clinical trial primarily aimed to investigate the effects of blonanserin on social functioning in patients with first-episode schizophrenia. Methods: In this prospective, multi-centre, single-arm clinical trial study, blonanserin (flexible oral dose ranging from 8mg to 24mg per day) was given 26 weeks. Outcome measures included the Personal and Social Performance (PSP) scale for evaluating social functioning, the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) for measuring neurocognitive performance, and the Positive and Negative Syndrome Scale (PANSS) for assessing symptom severity. The primary endpoint was social function improvement evaluated by PSP scale at the end of blonanserin treatment. And the secondary endpoint was to validate the efficacy and neurocognitive effects of blonanserin. Adverse drug reactions (ADRs) were also recorded and analysed. Results: A total of 96 patients with first-episode schizophrenia were recruited and proceeded to analysis. Fifty-one participants (53.1%) completed the PSP scale measurements at baseline and week 26. Following 26 weeks of blonanserin treatment, all outcome measurements demonstrated significant improvement during the follow-up period. Notably, PSP scores exhibited a continuous increase up to 68.1% ± 103.7% at the end of the treatment (46.6 ± 14.6 at baseline, 69.4 ± 17.4 at week 26, p<0.001), indicating positive effects on social functioning that were already noticeable by week 8. Conclusion: Blonanserin treatment exhibited favourable effects on social functioning in individuals with first-episode schizophrenia. The results suggest that blonanserin was effective treatment options for patients with schizophrenia encountering functional impairments.

CSF Findings in Chinese Patients with NMDAR, LGI1 and GABABR Antibody-Associated Encephalitis.

Purpose: CSF inflammation in subtypes of antibody-defined autoimmune encephalitis (AE) ranges in intensity from moderate to severe. In a retrospective, cross-sectional study, we characterized CSF findings in Chinese patients with anti-N-methyl-D-aspartate receptor encephalitis (NMDAR-E), anti-leucine-rich glioma-inactivated 1 encephalitis (LGI1-E), and anti-gamma aminobutyric acid-B receptor encephalitis (GABABR-E). Patients and Methods: The AE cases, including 102 NMDAR-E, 68 LGI1-E and 15 GABABR-E, were included. CSF inflammatory parameters consisted primarily of CSF leukocytes, oligoclonal bands (OCBs), and CSF/serum albumin ratios (QAlb). Ten serum cytokines were evaluated in order to classify AE subtypes. Results: 88% of NMDAR-E, 80% of GABABR-E, and 51% of LGI1-E patients had aberrant CSF features. In NMDAR-E, the CSF leukocyte count, CSF protein concentration, and age-adjusted QAlb were significantly higher than in LGI1-E, but did not differ from GABABR-E. Blood-CSF barrier dysfunction was less common in NMDAR-E patients with >40 years old. On admission, inflammatory CSF response was more prevalent in NMDAR-E patients with a higher CASE score. With age <60 years, CSF inflammatory changes were less frequent in LGI1-E patients, but more common in GABABR-E patients. MCP-1, IL-10, IL-1ß, and IL-4 were potential classifiers for NMDAR-E, LGI1-E, and GABABR-E, and correlated substantially with CSF leukocyte count and QAlb. Conclusion: Subtype-specific patterns are formed by the various inflammatory CSF parameters in NMDAR-E, LGI1-E, and GABABR-E, and their correlation with disease severity, age, and disease duration. CSF inflammatory characteristics associated with MCP-1, IL-10, IL-1ß, and IL-4 may be potential immunopathogeneses targeting markers for these AE subtypes.

Diagnostic signatures and immune cell infiltration characteristics in anti-GABABR encephalitis.

PURPOSE: Anti-gamma-aminobutyric acid B receptor (GABABR) encephalitis is an uncommon form of autoimmune encephalitis associated with a poor prognosis and a high fatality rate. We aim to find diagnostic markers for anti- GABABR encephalitis as well as the effects of immune cell infiltration on this pathology. METHODS: For quantitative proteomic analysis, isobaric tags for relative and absolute quantitation were used in conjunction with LC-MS/MS analysis. To conduct functional correlation analyses, differentially expressed proteins (DEPs) were identified. Following that, we used bioinformatics analysis to screen for and determine the diagnostic signatures of anti- GABABR encephalitis. ROC curves were used to evaluate the diagnostic values. To assess the inflammatory status of anti- GABABR encephalitis, we used cell-type identification by estimating relative subsets of the RNA transcript (CIBERSORT) and explored the link between diagnostic markers and infiltrating immune cells. RESULTS: Overall, 108 robust DEPs (47 upregulated and 61 downregulated) were identified, of which 11 were immune related. The most impressively enriched pathways were complemented and coagulation cascades, actin cytoskeleton regulation, and cholesterol metabolism; GSEA revealed that the enriched pathways were considerably differentially connected to immune modulation. Eleven immune-related DEPs were chosen for further investigation. We developed a novel diagnostic model based on CSF1R and AZGP1 serum levels using ROC analysis (area under the ROC curve = 1). M1 macrophages and activated natural killer cells are likely to play a role in course of anti- GABABR encephalitis. CONCLUSION: We identified CSF1R and AZGP1 are possible anti-GABABR encephalitis diagnostic indicators, and immune cell infiltration may have a significant impact on the development and occurrence of anti- GABABR encephalitis.

Cross-Spatiotemporal Graph Convolution Networks for Skeleton-Based Parkinsonian Gait MDS-UPDRS Score Estimation.

Gait impairment in Parkinson's Disease (PD) is quantitatively assessed using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), a well-established clinical tool. Objective and efficient PD gait assessment is crucial for developing interventions to slow or halt its advancement. Skeleton-based PD gait MDS-UPDRS score estimation has attracted increasing interest in improving diagnostic efficiency and objectivity. However, previous works ignore the important cross-spacetime dependencies between joints in PD gait. Moreover, existing PD gait skeleton datasets are very small, which is a big issue in deep learning-based gait studies. In this work, we collect a sizable PD gait skeleton dataset by multi-view Azure Kinect sensors. The collected dataset contains 102 PD patients and 30 healthy older adults. In addition, gait data from 16 young adults (aged 24-50 years) are collected to further examine the effect of age on PD gait assessment. For skeleton-based automatic PD gait analysis, we propose a novel cross-spatiotemporal graph convolution network (CST-GCN) to learn complex features of gait patterns. Specifically, a gait graph labeling strategy is designed to assemble and group cross-spacetime neighbors of the root node according to the spatiotemporal semantics of the gait skeleton. Based on this strategy, the CST-GCN module explicitly models the cross-spacetime dependencies among joints. Finally, a dual-path model is presented to realize the modeling and fusion of spatial, temporal, and cross-spacetime gait features. Extensive experiments validate the effectiveness of our method on the collected dataset.

Effects of microbial deodorizer on pig feces fermentation and the underlying deodorizing mechanism.

Microbial deodorization is a novel strategy for reducing odor in livestock and poultry feces. Herein, 12 strains of ammonia (NH3) and 15 hydrogen sulfide (H2S) removing bacteria were obtained with a removal efficiency of 65.20-79.80% and 34.90-79.70%, respectively. A novel bacteria deodorant named MIX (Bacillus zhangzhouensis, Bacillus altitudinis, and Acinetobacter pittii at a ratio of 1:1:2) were obtained. MIX can shorten the temperature rising stage by 2 days and prolong the thermophilic stage by 4 days. The ability of MIX to remove NH3, H2S, and volatile fatty acids (VFAs) and the underlying removal mechanism were analyzed during pig feces fermentation. MIX can significantly reduce the concentrations of NH3 and H2S by 41.82% and 66.35% and increase the concentrations of NO3--N and SO42- by 7.80% and 8.83% (P < 0.05), respectively, on the 25th day. Moreover, the concentrations of acetic, propionate, iso-valerate, and valerate were significantly reduced. The dominant bacteria communities at the phylum level were Firmicutes, Proteobacteria, Bacteroidetes, and Spirochaetes. B. zhangzhouensis and B. altitudinis could convert NH4+-N to NO3--N, and A. pittii could transfer H2S to SO42-. This study revealed that bacteria deodorant can reduce the concentrations of NH3, H2S, and VFAs in pig feces and increase those of NH4+, NO3-, and SO42- and has excellent potential in deodorizing livestock and poultry feces composting.

Functional-Group-Induced Single Quantum Well Dion-Jacobson 2D Perovskite for Efficient and Stable Inverted Perovskite Solar Cells.

In two-dimensional/three-dimensional (2D/3D) perovskite heterostructure, randomly distributed multiple quantum wells (QW) 2D perovskites are frequently generated, which are detrimental to carrier transport and structural stability. Here, the high quality 2D/3D perovskite heterostructure is constructed by fabricating functional-group-induced single QW Dion-Jacobson (DJ) 2D perovskites. The utilization of ─OCH3 in the precursor solution facilitates the formation of colloidal particles with uniform size, resulting in the production of a pure 2D DJ perovskite with an n value of 3. This strategy facilitates the improvement of 3D structural stability and expedites carrier transport. The resultant devices accomplish a power conversion efficiency of 25.26% (certified 25.04%) and 23.56% at a larger area (1 cm2 ) with negligible hysteresis. The devices maintain >96% and >89% of their initial efficiency after continuous maximum power point tracking under simulated AM1.5 illumination for 1300 h and under damp-heat conditions (85 °C and 85% RH) for 1010 h, respectively.

Optimizing functional zoning for Dalingshan Forest Park in China through microcosmic human disturbance evaluation.

Human disturbance stands as a prominent factor influencing the ecological environment within natural protected areas. Presently, the issue of balancing human activities and ecological preservation has emerged as a critical concern in the construction of China's natural protected area system. Functional zoning serves as the cornerstone of natural protected area management and represents a pivotal tool in achieving this equilibrium. This study endeavors to introduce a set of functional zoning methods for natural protected areas based on human disturbance assessments. Utilizing Dalingshan Forest Park in Dongguan city which is known for its significant human disturbances as a case study, field surveys were conducted to identify various types of small-scale and understory-hidden human disturbances, such as residential areas, roads, tourist areas, forestry areas, and energy facilities. Subsequently, a microcosmic human disturbance model tailored to forested areas was developed using the analytic hierarchy process. By integrating the findings of macrocosmic human disturbance assessments conducted concurrently by the research group, a functional zoning plan for Dalingshan Forest Park was proposed. The results show that ecological conservation zones within the park should be established in three specific areas, primarily in regions with low-level microcosmic human disturbance (levels 1 and 2) and terrain fluctuations ≥110 m. In contrast, the rational use zone is notably influenced by tourist infrastructure and road networks, predominantly located in regions with high human activity, such as popular tourist destinations and areas with road classifications and vehicular traffic. The microcosmic human disturbance assessment method proposed in this study enhances the rationality and accuracy of natural protected area functional zoning. It provides a more scientifically grounded research approach for similar studies concerning natural protected area functional zoning and contributes valuable insights for the further advancement of China's efforts in the integration and optimization of natural protected areas.

Performance of aerobic denitrifying fungal community for promoting nitrogen reduction and its application in drinking water reservoirs.

The effect of mix-cultured aerobic denitrifying microorganisms on the water remediation has been extensively explored, but little is known about the performance of mix-cultured low efficiency fungi on denitrification. In this study, two kinds of aerobic denitrifying fungi (Trichoderma afroharzianum H1 and Aspergillus niger C1) were isolated from reservoirs, improved the capacity by mix-cultured. The results showed a difference between northern and southern reservoirs, the dominants of genera were Cystobasidium and Acremonium. The removals of total nitrogen (TN) was 12.00%, 7.53% and 69.33% in Trichoderma afroharzianum H1, Aspergillus niger C1 and mix-cultured (C1 and H1) under the denitrification medium. The contents of ATP and electron transport system activity in mix-cultured amendment were increased by 42.54% and 67.52%, 1.72 and 2.91 times, respectively. Besides, the raw water experiment indicated that TN removals were 24.05%, 12.66% and 73.42% in Trichoderma afroharzianum H1, Aspergillus niger C1 and mix-cultured. The removals of dissolved organic carbon in mix-cultured were increased 35.02% and 50.46% compared to Trichoderma afroharzianum H1 and Aspergillus niger C1. Therefore, mix-cultured of two low efficiency aerobic denitrifying fungi has been considered as a novelty perspective for mitigation of drinking water source.

Effects of Peripherally inserted Central Catheter (PICC) materials and designs on reduction of PICC-related complications: A systematic review and meta-analysis.

Studies showed that integrating coating or valve into Peripherally Inserted Central (PICC) can prevent related complications. However, data regarding efficiency were controversial. Therefore, a systematic review was needed to analyse the effect of PICC materials and designs on reduction of PICC-related complications. We searched PubMed, Cochrane library, EMbase, grey literature and referent literature from inception to 5 August 2022. Randomized controlled trials (RCTs) and case-control study were included. Two authors extracted data independently, using a predesigned Excel form, and assessed the quality of included RCTs according to the Cochrane Handbook for Systematic Reviews (V5.1.0), case-control study was assessed by the Newcastle-Ottawa Scale. Data were analysed using Review Manager (v5.3.0). A total of 10 RCTs and one case-control study were included. Meta-analysis results showed that PICC designs reduce the incidence of obstruction, and at the critical value of PICC-associated bloodstream infection, but may have no effects on other complications. Based on the literature reviewed, we can only say PICC new materials did not reflect significant reduction on complications, what's more, the result needs more multicentre, large RCTs to support. We suggested clinicians combine descriptive research and cost-effect analysis to select appropriate PICC materials and designs for patients.

FoxO1 knockdown inhibits RANKL-induced osteoclastogenesis by blocking NLRP3 inflammasome activation.

OBJECTIVES: This study aimed to elucidate the connection between osteoclastic forkhead transcription factor O1 (FoxO1) and periodontitis and explore the underlying mechanism by which FoxO1 knockdown regulates osteoclast formation. MATERIALS AND METHODS: A conventional ligature-induced periodontitis model was constructed to reveal the alterations in the proportion of osteoclastic FoxO1 in periodontitis via immunofluorescence staining. Additionally, RNA sequencing (RNA-seq) was performed to explore the underlying mechanisms of FoxO1 knockdown-mediated osteoclastogenesis, followed by western blotting, quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay. RESULTS: FoxO1+ osteoclasts were enriched in the alveolar bone in experimental periodontitis. Moreover, FoxO1 knockdown led to impaired osteoclastogenesis with low expression of osteoclast differentiation-related genes, accompanied by an insufficient osteoclast maturation phenotype. Mechanistically, RNA-seq revealed that the nuclear factor kappa B (NF-κB) and nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome signaling pathways were inhibited in FoxO1-knockdown osteoclasts. Consistent with this, MCC950, an effective inhibitor of the NLRP3 inflammasome, substantially attenuated osteoclast formation. CONCLUSIONS: FoxO1 knockdown contributed to the inhibition of osteoclastogenesis by effectively suppressing NF-κB signaling and NLRP3 inflammasome activation. This prospective study reveals the role of FoxO1 in mediating osteoclastogenesis and provides a viable therapeutic target for periodontitis treatment.

Nonivamide inhibits proliferation of human corneal epithelial cells by inducing cell cycle arrest and oxidative stress.

Nonivamide, an agonist of transient receptor potential vanilloid type 1 (TRPV1), is widely used as a riot control agent, police incapacitant spray and pesticide. Although generally considered non-fatal, eye discomfort and even ocular injuries caused by such products are common. Little research has been conducted on the effects of nonivamide on corneal epithelial cells. Cell viability, impedance, flow cytometry, western blotting, and real-time fluorescence analyses were performed to investigate the effects of nonivamide on human corneal epithelial cells (HCE-T cells). We found that nonivamide impaired proliferation at subtoxic doses (100 µM and 200 µM) in HCE-T cells. Next, we described the mechanisms of action of nonivamide. Nonivamide caused cell cycle arrest by increasing p21 and decreasing cyclin D1. TRPV1 was activated by nonivamide, leading to an influx of Ca2+. Enhanced Ca2+ influx partially contributed to oxidative stress. Mitochondrial membrane potential (MMP) also decreased. All combined stress resulted in the inhibition of cell proliferation in HCE-T cells. In summary, nonivamide inhibited the proliferation of HCE-T cells at sub-toxic doses by inducing cell cycle arrest and oxidative stress. Our data demonstrate the corneal toxicity of nonivamide and explain the mechanisms underlying nonivamide-induced corneal injury.

Kaolinite reduced Cd accumulation in peanut and remediate soil contaminated with both microplastics and cadmium.

Microplastics (MPs) increase the effective state of heavy metals (HMs) in soil and seriously threaten the yield and quality of peanuts (Arachis Hypogea L.). Kaolinite (KL) has the potential to ameliorate MP- and HM- contaminated soils, but the mechanism of action between them is not well understood. Therefore, 60-day experiments were conducted, where KL (1 %, 2 %) and MPs (0.1 %, 1 %) were individually or jointly mixed into soils with different cadmium (Cd) concentrations (0.5, 2.5, and 5.0 mg·kg-1) to cultivate peanuts in a greenhouse. Finally, soil-bioavailable Cd, peanut dry weight, peanut Cd concentrations, the pH, cation exchange capacity (CEC), dissolved organic carbon (DOC), microbial biomass carbon (MBC) and microbial biomass nitrogen (MBN) were determined. It was shown that MPs negatively affected the peanut dry weight and increased the content of soil-bioavailable Cd and Cd concentration in peanut. In the MP- and Cd-contaminated soils, KL mitigated the negative influence of MPs by increasing the dry weight of peanuts by 8.40 %-40.59 %, decreasing the soil-bioavailable Cd by 23.70-35.74 %, and significantly decreasing peanut Cd concentrations by 9.65-30.86 %. The presence of MPs decreased soil pH (7.69-7.87) and the CEC (20.96-23.95 cmol·L-1) and increased the soil DOC (1.84-2.26 mg·kg-1). KL significantly increased soil pH (7.79-8.03) and the CEC (24.96-28.28 cmol·L-1) and mitigated the adverse influence of MPs on the pH and CEC of Cd-contaminated soils. A regression path analysis (RPA) evidenced that KL decreased Cd accumulation in plants by changing the properties of soil contaminated with MPs and Cd. The research results revealed the mechanism of KL on peanut growth and Cd absorption in MP- and Cd-contaminated soil. The results of this study provide a foundation to improve the quality of MP- and HM-contaminated soils and realize safe peanut production.

Safety and effectiveness of oral medium to high dose blonanserin in patients with schizophrenia: subgroup analysis from a prospective, multicenter, post-marketing surveillance study in mainland China.

BACKGROUND: Blonanserin (BNS) had been undergoing post-market surveillance (PMS) since September 2018. Using the surveillance data, we did this analysis to assess the safety and effectiveness of different doses of BNS to explore a sufficient dose range of BNS in Chinese patients with schizophrenia (SZ). METHODS: A 12-week, prospective, observational, single-arm, multicenter, open-label PMS was conducted. In this analysis, we divided the patients from PMS into low, medium to high, and high dose groups based on the dose of BNS they received, with medium to high dose group being the focus. The Brief Psychiatric Rating Scale (BPRS) scores at week 2 or 4, 6 or 8, and 12 were calculated to evaluate the effectiveness of BNS in improving psychiatric symptoms. The safety of BNS was reported as the incidence of adverse drug reactions. RESULTS: 364 patients were included in the medium to high dose group, of which 321 completed the surveillance, with a dropout rate of 11.8%. The mean daily dose was 15.1 ± 1.92 mg. The BPRS total score was 50.1 ± 11.95 at baseline and decreased to 26.6 ± 7.43 at 12 weeks (P < 0.001). When compared with other groups, the median to high dose group achieved significantly more reduction in BPRS score at week 12 (P = 0.004 versus low dose and P = 0.033 versus higher dose). Extrapyramidal symptoms [EPS (46.4%)] were the most common adverse reactions in the medium to high group. The average weight gain during the surveillance was 0.5 ± 2.56 kg and prolactin elevation occurred in 2.2% patients. Most adverse reactions were mild. CONCLUSIONS: BNS at medium to high doses (mean 15.1 mg/d) significantly improved symptoms of SZ and was well-tolerated. Most ADRs were mild, and the likelihood of causing metabolic side effects and prolactin elevations was low. Medium to high dose of BNS is a more potent treatment choice for SZ. TRIAL REGISTRATION NUMBER: ChiCTR2100048734. Date of registration: 2021/07/15 (retrospectively registered).

Different Size Formulations of Fluopyram: Preparation, Antifungal Activity, and Accumulation in the Fungal Pathogen Botrytis cinerea.

Nanotechnology is revolutionizing the efficient production and sustainable development of modern agriculture. Understanding the pesticide activity of both nano- and conventional methods is useful for developing new pesticide formulations. In this study, three solid fluopyram formulations with varying particle sizes were developed, and the mechanisms underlying the difference in the antifungal activity among these formulations were investigated. Wet media milling combined with freeze drying was used to prepare fluopyram nanoparticles (FLU-NS) and a micron-sized solid formulation (FLU-MS), and a jet grinding mill was employed to fabricate fluopyram wettable powder (FLU-WP). The mean particle sizes of FLU-NS, FLU-MS, and FLU-WP were 366.8 nm, 2.99 µm, and 10.16 µm, respectively. Notably, FLU-NS displayed a toxicity index against Botrytis cinerea (gray mold) that was approximately double those of FLU-MS and FLU-WP. Similar trends were noticed in the antifungal tests on Alternaria solani. The uptake of FLU-NS by B. cinerea was approximately twice that of FLU-MS and FLU-WP, indicating that fluopyram nanoparticles are more easily taken up by the pathogen (B. cinerea), and display better bioactivity than the larger fluopyram particles. Therefore, the nanosizing of pesticides appears to be a viable strategy to enhance efficiency without increasing the amount of pesticide used.