Cerebellum and social abilities: A structural and functional connectivity study in a transdiagnostic sample.

The cerebellum has been involved in social abilities and autism. Given that the cerebellum is connected to the cortex via the cerebello-thalamo-cortical loop, the connectivity between the cerebellum and cortical regions involved in social interactions, that is, the right temporo-parietal junction (rTPJ) has been studied in individuals with autism, who suffer from prototypical deficits in social abilities. However, existing studies with small samples of categorical, case-control comparisons have yielded inconsistent results due to the inherent heterogeneity of autism, suggesting that investigating how clinical dimensions are related to cerebellar-rTPJ functional connectivity might be more relevant. Therefore, our objective was to study the functional connectivity between the cerebellum and rTPJ, focusing on its association with social abilities from a dimensional perspective in a transdiagnostic sample. We analyzed structural magnetic resonance imaging (MRI) and functional MRI (fMRI) scans obtained during naturalistic films watching from a large transdiagnostic dataset, the Healthy Brain Network (HBN), and examined the association between cerebellum-rTPJ functional connectivity and social abilities measured with the social responsiveness scale (SRS). We conducted univariate seed-to-voxel analysis, multivariate canonical correlation analysis (CCA), and predictive support vector regression (SVR). We included 1404 subjects in the structural analysis (age: 10.516 ± 3.034, range: 5.822-21.820, 506 females) and 414 subjects in the functional analysis (age: 11.260 ± 3.318 years, range: 6.020-21.820, 161 females). Our CCA model revealed a significant association between cerebellum-rTPJ functional connectivity, full-scale IQ (FSIQ) and SRS scores. However, this effect was primarily driven by FSIQ as suggested by SVR and univariate seed-to-voxel analysis. We also demonstrated the specificity of the rTPJ and the influence of structural anatomy in this association. Our results suggest that there is a complex relationship between cerebellum-rTPJ connectivity, social performance and IQ. This relationship is specific to the cerebellum-rTPJ connectivity, and is largely related to structural anatomy in these two regions. PRACTITIONER POINTS: We analyzed cerebellum-right temporoparietal junction (rTPJ) connectivity in a pediatric transdiagnostic sample. We found a complex relationship between cerebellum and rTPJ connectivity, social performance and IQ. Cerebellum and rTPJ functional connectivity is related to structural anatomy in these two regions.

Radiotherapy for patients with locally advanced esophageal squamous cell carcinoma receiving neoadjuvant immunotherapy combined with chemotherapy.

With the success of immunotherapy in advanced esophageal cancer, neoadjuvant chemo-immunotherapy (CIT) is being increasingly used for local staged esophageal cancer, especially in the context of clinical trials, which brings similar pCR with neoadjuvant chemoradiotherapy and shows promising results. However, there is still a part of potentially operable patients can't undergo surgery after neoadjuvant chemo-immunotherapy. The follow-up treatment and prognosis of this population remain unclear. Patients pathologically diagnosed with ESCC, clinical stage T1-3N+M0 or T3-4aNanyM0 (AJCC 8th), PS 0-1 were retrospectively enrolled from 1/2020 to 6/2021 in Zhejiang Cancer Hospital. All patients firstly received PD-1 inhibitors plus chemotherapy (albumin paclitaxel, 260 mg/m2 on day 1 plus carboplatin AUC = 5 on day 1) every 3 weeks for 2-4 cycles. For those patients who did not receive surgery, definitive radiotherapy with 50.4 Gy/28F or 50 Gy/25F was adopted using VMAT, concurrent with chemotherapy or alone. The concurrent chemotherapy regimens included weekly TC (paclitaxel 50 mg/m2, d1, carboplatin AUC = 2, d1) or S1 (60 mg bid d1-14, 29-42). The survival outcomes and treatment toxicity were recorded and analyzed. A total of 56 eligible patients were finally identified from 558 patients who were treated in department of thoracic surgery, among all the patients, 25 (44.6%) received radiotherapy alone, and 31 (55.4%) received chemoradiotherapy after neoadjuvant CIT. The median follow-up was 20.4 months (interquartile range [IQR] 8.7-27 months). The median PFS and OS were 17.9 months (95% confidence interval [CI] 11.0-21.9 months) and 20.5 months (95% CI 11.8-27.9 months), respectively. In the subgroup analysis, the median OS was 26.3 months (95% CI 15.33-NA) for patients exhibiting partial response (PR) to CIT, compared to 17 months (95% CI 8.77-26.4) for those with stable disease (SD) or progressive disease (PD), yielding a hazard ratio (HR) of 0.54 (95% CI 0.27-1.06, P = 0.07). No significant difference was observed for patients received radiotherapy alone or chemoradiotherapy with HR = 0.73 (95% CI 0.72-2.6, P = 0.33). The most common Adverse events (AEs) observed during this study were anemia (98.2%), leukopenia (83.9%), thrombocytopenia (53.6%). AEs of grade ≥ 3 radiation-induced pneumonitis and esophagitis were 12.5% and 32.1%, especially, 6 patients (10.7%) died from esophageal fistula and 2 patients (3.6%) died from grade 5 pneumonitis. For local advanced ESCC patients after neoadjuvant CIT who did not receive surgery, definitive radiotherapy was an optional treatment strategy. However, those patients with no response to CIT also showed poor response to radiotherapy, and particular attention should be paid to treatment related toxicity, especially esophageal fistula.

Downregulation of CASC15 attenuates the symptoms of polycystic ovary syndrome by affecting granulosa cell proliferation and regulating ovarian follicular development.

Polycystic ovary syndrome (PCOS) is a type of follicular dysplasia with an unclear pathogenesis, posing certain challenges in its diagnosis and treatment. Cancer susceptibility candidate 15 (CASC15), a long non-coding RNA closely associated with tumour development, has been implicated in PCOS onset and development. Therefore, this study aimed to investigate the molecular mechanisms underlying PCOS by downregulating CASC15 expression in both in vitro and in vivo models. We explored the potential regulatory relationship between CASC15 expression and PCOS by examining cell proliferation, cell cycle dynamics, cell autophagy, steroid hormone secretion capacity, and overall ovarian function in mice. We found that CASC15 expression in granulosa cells derived from patients with PCOS was significantly higher than those of the normal group (P < 0.001). In vitro experiments revealed that downregulating CASC15 significantly inhibited cell proliferation, promoted apoptosis, induced G1-phase cell cycle arrest, and influenced cellular autophagy levels. Moreover, downregulating CASC15 affected the follicular development process in newborn mouse ovaries. In vivo studies in mice demonstrated that disrupting CASC15 expression improved PCOS-related symptoms such as polycystic changes and hyperandrogenism, and significantly affected ovulation induction and embryo implantation in pregnant mice. Overall, CASC15 was highly expressed in granulosa cells of patients with PCOS and its downregulation improved PCOS-related symptoms by influencing granulosa cell function and follicular development in mice.

SVHRSP Alleviates Age-Related Cognitive Deficiency by Reducing Oxidative Stress and Neuroinflammation.

BACKGROUND: Our previous studies have shown that scorpion venom heat-resistant synthesized peptide (SVHRSP) induces a significant extension in lifespan and improvements in age-related physiological functions in worms. However, the mechanism underlying the potential anti-aging effects of SVHRSP in mammals remains elusive. METHODS: Following SVHRSP treatment in senescence-accelerated mouse resistant 1 (SAMR1) or senescence-accelerated mouse prone 8 (SAMP8) mice, behavioral tests were conducted and brain tissues were collected for morphological analysis, electrophysiology experiments, flow cytometry, and protein or gene expression. The human neuroblastoma cell line (SH-SY5Y) was subjected to H2O2 treatment in cell experiments, aiming to establish a cytotoxic model that mimics cellular senescence. This model was utilized to investigate the regulatory mechanisms underlying oxidative stress and neuroinflammation associated with age-related cognitive impairment mediated by SVHRSP. RESULTS: SVHRSP significantly ameliorated age-related cognitive decline, enhanced long-term potentiation, restored synaptic loss, and upregulated the expression of synaptic proteins, therefore indicating an improvement in synaptic plasticity. Moreover, SVHRSP demonstrated a decline in senescent markers, including SA-ß-gal enzyme activity, P16, P21, SIRT1, and cell cycle arrest. The underlying mechanisms involve an upregulation of antioxidant enzyme activity and a reduction in oxidative stress-induced damage. Furthermore, SVHRSP regulated the nucleoplasmic distribution of NRF2 through the SIRT1-P53 pathway. Further investigation indicated a reduction in the expression of proinflammatory factors in the brain after SVHRSP treatment. SVHRSP attenuated neuroinflammation by regulating the NF-κB nucleoplasmic distribution and inhibiting microglial and astrocytic activation through the SIRT1-NF-κB pathway. Additionally, SVHRSP significantly augmented Nissl body count while suppressing neuronal loss. CONCLUSION: SVHRSP could remarkably improve cognitive deficiency by inhibiting oxidative stress and neuroinflammation, thus representing an effective strategy to improve brain health.

Scorpion venom heat-resistant synthesized peptide ameliorates epileptic seizures and imparts neuroprotection in rats mediated by NMDA receptors.

Finding new and effective natural products for designing antiepileptic drugs is highly important in the scientific community. The scorpion venom heat-resistant peptide (SVHRP) was purified from Buthus martensii Karsch scorpion venom, and subsequent analysis of the amino acid sequence facilitated the synthesis of a peptide known as scorpion venom heat-resistant synthesis peptide (SVHRSP) using a technique for peptide synthesis. Previous studies have demonstrated that the SVHRSP can inhibit neuroinflammation and provide neuroprotection. This study aimed to investigate the antiepileptic effect of SVHRSP on both acute and chronic kindling seizure models by inducing seizures in male rats through intraperitoneal administration of pentylenetetrazole (PTZ). Additionally, an N-methyl-D-aspartate (NMDA)-induced neuronal injury model was used to observe the anti-excitotoxic effect of SVHRSP in vitro. Our findings showed that treatment with SVHRSP effectively alleviated seizure severity, prolonged latency, and attenuated neuronal loss and glial cell activation. It also demonstrated the prevention of alterations in the expression levels of NMDA receptor subunits and phosphorylated p38 MAPK protein, as well as an improvement in spatial reference memory impairment during Morris water maze (MWM) testing in PTZ-kindled rats. In vitro experiments further revealed that SVHRSP was capable of attenuating neuronal action potential firing, inhibiting NMDA receptor currents and intracellular calcium overload, and reducing neuronal injury. These results suggest that the antiepileptic and neuroprotective effects of SVHRSP may be mediated through the regulation of NMDA receptor function and expression. This study provides new insight into therapeutic strategies for epilepsy.

Integrative single-cell and bulk transcriptomes analyses reveals heterogeneity of serine-glycine-one-carbon metabolism with distinct prognoses and therapeutic vulnerabilities in HNSCC.

Metabolic heterogeneity plays a central role in sustaining uncontrolled cancer cell proliferation and shaping the tumor microenvironment (TME), which significantly compromises the clinical outcomes and responses to therapy in head and neck squamous cell carcinoma (HNSCC) patients. This highlights the urgent need to delineate the intrinsic heterogeneity and biological roles of metabolic vulnerabilities to advance precision oncology. The metabolic heterogeneity of malignant cells was identified using single-cell RNA sequencing (scRNA-seq) profiles and validated through bulk transcriptomes. Serine-glycine-one-carbon (SGOC) metabolism was screened out to be responsible for the aggressive malignant properties and poor prognosis in HNSCC patients. A 4-SGOC gene prognostic signature, constructed by LASSO-COX regression analysis, demonstrated good predictive performance for overall survival and therapeutic responses. Patients in the low-risk group exhibited greater infiltration of exhausted CD8+ T cells, and demonstrated better clinical outcomes after receiving immunotherapy and chemotherapy. Conversely, high-risk patients exhibited characteristics of cold tumors, with enhanced IMPDH1-mediated purine biosynthesis, resulting in poor responses to current therapies. IMPDH1 emerged as a potential therapeutic metabolic target. Treatment with IMPDH inhibitors effectively suppressed HNSCC cell proliferation and metastasis and induced apoptosis in vitro and in vivo by triggering GTP-exhaustion nucleolar stress. Our findings underscore the metabolic vulnerabilities of HNSCC in facilitating accurate patient stratification and individualized precise metabolic-targeted treatment.

ASS1 Enhances Anoikis Resistance via AMPK/CPT1A-mediated Fatty Acid Metabolism in Ovarian Cancer.

Metastasis is the leading cause of death in ovarian cancer (OC), with anoikis resistance being a crucial step for detached OC cells survival. Despite extensive research, targeting anoikis resistance remians a challenge. Here, we identify argininosuccinate synthase 1 (ASS1), a key enzyme in urea cycle, is markedly upregulated in OC cells in detached culture and is associated with increased anoikis resistance and metastasis. Disruption of the AMP/ATP balance by elevated ASS1 activates AMPK and its downstream factor, CPT1A. Then, ASS1 enhances FAO, leading to higher ATP generation and lipid utilization. Inhibition of CPT1A reverses ASS1-induced FAO. Our study gives some new functional insights into OC metabolism and represents a shift from traditional views, expanding ASS1's relevance beyond nitrogen metabolism to fatty acid metabolism. It uncovers how ASS1-induced FAO disrupts the AMP/ATP balance, leading to AMPK activation. By identifying the ASS1/AMPK/CPT1A axis as crucial for OC anoikis resistance and metastasis, our study opens up new avenues for therapeutic interventions.

Ecofriendly Controlled-Release Insecticide Carrier: pH-/Temperature-Responsive Rosin-Derived Hydrogels for Avermectin Delivery against Mythimna separata (Walker).

The exploration of environmentally friendly, less toxic, sustained-release insecticide is increasing with the growing demand for food to meet the requirements of the expanding population. As a sustained-release carrier, the unique, environmentally friendly intelligent responsive hydrogel system is an important factor in improving the efficiency of insecticide utilization and accurate release. In this study, we developed a facile approach for incorporating the natural compound rosin (dehydroabietic acid, DA) and zinc ions (Zn2+) into a poly(N-isopropylacrylamide) (PNIPAM) hydrogel network to construct a controlled-release hydrogel carrier (DA-PNIPAM-Zn2+). Then, the model insecticide avermectin (AVM) was encapsulated in the carrier at a drug loading rate of 36.32% to form AVM@DA-PNIPAM-Zn2+. Surprisingly, the smart controlled carrier exhibited environmental responsiveness, strongly enhanced mechanical properties, self-healing ability, hydrophobicity, and photostability to ensure a balance between environmental friendliness and the precision of the drug release. The release experiments showed that the carboxyl and amide groups in the polymer chains alter the intermolecular forces within the hydrogel meshes and ingredient diffusion by changing temperatures (25 and 40 °C) and pH values (5.8, 7.4, and 8.5), leading to different release behaviors. The insecticidal activity of the AVM@DA-PNIPAM-Zn2+ against oriental armyworms was good, with an effective minimum toxicity toward aquatic animals. Therefore, AVM@DA-PNIPAM-Zn2+ is an effective drug delivery system against oriental armyworms. We anticipate that this ecofriendly, sustainable, smart-response carrier may broaden the utilization rosin and its possible applications in the agricultural sector.

Rational and design of prophylactic cranial irradiation (PCI) and brain MRI surveillance versus brain MRI surveillance alone in patients with limited-stage small cell lung cancer achieving complete remission (CR) of tumor after chemoradiotherapy: a multicenter prospective randomized study.

BACKGROUND: Prophylactic cranial irradiation (PCI) is part of standard care in limited-stage small cell lung cancer (SCLC) at present. As evidence from retrospective studies increases, the benefits of PCI for limited-stage SCLC are being challenged. METHODS: A multicenter, prospective, randomized controlled study was designed. The key inclusion criteria were: histologically or cytologically confirmed small cell carcinoma, age ≥ 18 years, KPS ≥ 80, limited-stage is defined as tumor confined to one side of the chest including ipsilateral hilar, bilateral mediastinum and supraclavicular lymph nodes, patients have received definitive thoracic radiotherapy (regardless of the dose-fractionation of radiotherapy used) and chemotherapy, evaluated as complete remission (CR) of tumor 4-6 weeks after the completion of chemo-radiotherapy. Eligible patients will be randomly assigned to two arms: (1) PCI and brain MRI surveillance arm, receiving PCI (2.5 Gy qd to a total dose of 25 Gy in two weeks) followed by brain MRI surveillance once every three months for two years; (2) brain MRI surveillance alone arm, undergoing brain MRI surveillance once every three months for two years. The primary objective is to compare the 2-year brain metastasis-free survival (BMFS) rates between the two arms. Secondary objectives include 2-year overall survival (OS) rates, intra-cranial failure patterns, 2-year progression-free survival rates and neurotoxicity. In case of brain metastasis (BM) detect during follow-up, stereotactic radiosurgery (SRS) will be recommended if patients meet the eligibility criteria. DISCUSSION: Based on our post-hoc analysis of a prospective study, we hypothesize that in limited-stage SCLC patients with CR after definitive chemoradiotherapy, and ruling out of BM by MRI, it would be feasible to use brain MRI surveillance and omit PCI in these patients. If BM is detected during follow-up, treatment with SRS or whole brain radiotherapy does not appear to have a detrimental effect on OS. Additionally, this approach may reduce potential neurotoxicity associated with PCI.

Recent Advances in Dopamine-Based Membrane Surface Modification and Its Membrane Distillation Applications.

Surface modification of membranes is essential for improving flux and resistance to contamination for membranes. This is of great significance for membrane distillation, which relies on the vapor pressure difference across the membrane as the driving force. In recent years, biomimetic mussel-inspired substances have become the research hotspots. Among them, dopamine serves as surface modifiers that would achieve highly desirable and effective membrane applications owing to their unique physicochemical properties, such as universal adhesion, enhanced hydrophilicity, tunable reducibility, and excellent thermal conductivity. The incorporation of a hydrophilic layer, along with the utilization of photothermal properties and post-functionalization capabilities in modified membranes, effectively addresses challenges such as low flux, contamination susceptibility, and temperature polarization during membrane distillation. However, to the best of our knowledge, there is still a lack of comprehensive and in-depth discussions. Therefore, this paper systematically compiles the modification method of dopamine on the membrane surface and summarizes its application and mechanism in membrane distillation for the first time. It is believed that this paper would provide a reference for dopamine-assisted membrane separation during production, and further promote its practical application.

PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma: A case report.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal disease with limited effective treatment especially after first-line chemotherapy. The human epidermal growth factor receptor 2 (HER-2) immunohistochemistry (IHC) positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC. CASE SUMMARY: We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn't have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment. A novel combination therapy PRaG 3.0 of RC48 (HER2-antibody-drug conjugate), radiotherapy, PD-1 inhibitor, granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month. She had not developed any grade 2 or above treatment-related adverse events at any point. Percentage of peripheral CD8+Temra and CD4+Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy. CONCLUSION: PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.

Inhibition of ESCRT-independent extracellular vesicles biogenesis suppresses enterovirus 71 replication and pathogenesis in mice.

Enterovirus 71 (EV71) causes hand-foot-and-mouth disease (HFMD), neurological complications, and even fatalities in infants. Clinically, the increase of extracellular vesicles (EVs) in EV71 patients' serum was highly associated with the severity of HFMD. EV71 boosts EVs biogenesis in an endosomal sorting complex required for transport (ESCRT)-dependent manner to facilitate viral replication. Yet, the impact of EVs-derived from ESCRT-independent pathway on EV71 replication and pathogenesis is highly concerned. Here, we assessed the effects of EV71-induced EVs from ESCRT-independent pathway on viral replication and pathogenesis by GW4869, a neutral sphingomyelinase inhibitor. Detailly, in EV71-infected mice, blockade of the biogenesis of tissue-derived EVs in the presence of GW4869 restored body weight loss, attenuated clinical scores, and improved survival rates. Furthermore, GW4869 dampens EVs biogenesis to reduce viral load and pathogenesis in multiple tissues of EV71-infected mice. Consistently, GW4869 treatment in a human intestinal epithelial HT29 cells decreased the biogenesis of EVs, in which the progeny EV71 particle was cloaked, leading to the reduction of viral infection and replication. Collectively, GW4869 inhibits EV71-induced EVs in an ESCRT-independent pathway and ultimately suppresses EV71 replication and pathogenesis. Our study provides a novel strategy for the development of therapeutic agents in the treatment for EV71-associated HFMD.

Efficient Control of Rhizoctonia solani Using Environmentally Friendly pH-Responsive Tannic Acid-Rosin Nano-Microcapsules.

A nanomicrocapsule system was constructed through the polymerization of tannic acid (TA) and emulsifier OP-10 (OP-10), followed by the chelation of iron ions, to develop a safe and effective method for controlling Rhizoctonia solani in agriculture. The encapsulated active component is a rosin-based triazole derivative (RTD) previously synthesized by our research group (RTD@OP10-TA-Fe). The encapsulation efficiency of the nanomicrocapsules is 82.39%, with an effective compound loading capacity of 96.49%. Through the encapsulation of the RTD via nanomicrocapsules, we improved its water solubility, optimized its stability, and increased its adhesion to the leaf surface. Under acidic conditions (pH = 5.0), the release rate of nanomicrocapsules at 96 h is 96.31 ± 0.8%, which is 2.04 times higher than the release rate under normal conditions (pH = 7.0). Additionally, the results of in vitro and in vivo antifungal assays indicate that compared with the original compound, the nanomicrocapsules exhibit superior antifungal activity (EC50 values of RTD and RTD@OP10-TA-Fe are 1.237 and 0.860 mg/L, respectively). The results of field efficacy trials indicate that compared with RTD, RTD@OP10-TA-Fe exhibits a more prolonged period of effectiveness. Even after 3 weeks, the antifungal rate of RTD@OP10-TA-Fe remains at 40%, whereas RTD, owing to degradation, shows an antifungal rate of 11.11% during the same period. Furthermore, safety assessment results indicate that compared with the control, RTD@OP10-TA-Fe has almost no impact on the growth of rice seedlings and exhibits low toxicity to zebrafish. This study provides valuable insights into controlling R. solani and enhancing the compound performance.

Discovery of novel acrylopimaric acid triazole derivatives as promising antifungal agents.

BACKGROUND: To further develop potential natural fungicides, two series of new acrylopimaric acid triazole derivatives were synthesized, and their antifungal activities were tested and evaluated. RESULTS: In vitro antifungal activity results indicated that compound 5m exhibited significant inhibitory activity against Rhizoctonia solani with an half maximal effective concentration (EC50) value of 1.528 mg/L. Its antifungal effect was comparable to that of the commercially available fungicide fluconazole, epoxiconazole and propiconazole (EC50 values of 1.441, 0.815 and 1.173 mg/L). Subsequently, in vivo studies were conducted on compound 5m, which revealed its significant protective and curative effects against R. solani. In addition, physiological and biochemical studies showed that compound 5m could disrupt the morphology and ultrastructure of R. solani mycelium, increase cell membrane permeability, inhibit ergosterol synthesis, and enhance the activity of defense enzymes in rice plants. Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies revealed that the molecular structure significantly influenced the binding of compound 5m to the receptor, thereby enhancing its antifungal activity. CONCLUSION: Compound 5m exhibits excellent antifungal activity against R. solani, making it a promising candidate fungicide for the prevention and control of R. solani. © 2024 Society of Chemical Industry.

Discovery of Potential Rosin-Based Triazole Antifungal Candidates to Control Valsa mali for Sustainable Crop Protection.

To investigate the potential application value of dehydroabietic acid, 27 novel dehydroabietyl-1,2,4-triazole-5-thioether-based derivatives were designed and characterized by IR, 1H NMR, 13C NMR, and LC-MS. Their antifungal activities were evaluated against five plant fungi, namely, Valsa mali, Colletotrichum orbiculare, Fusarium graminearum, Sclerotinia sclerotiorum, and Gaeumannomyces graminis; the results showed that compound 5h-1 (Co. 5h-1) exhibited a considerable inhibitory effect against V. mali. Moreover, in vivo experiments indicated that Co. 5h-1 had a certain protective effect on apple branches. The preliminary structure-activity relationship analysis suggested that the electron-withdrawing group on the benzyl group was significantly better than that of other substituent derivatives. Through electron microscopy analysis, it was found that Co. 5h-1 hindered the growth of mycelia, damaged their cell structure, and caused the large accumulation of reactive oxygen species (ROS). Preliminary research on the mode of action indicated that Co. 5h-1 could affect the activity of CAT by increasing the α-helix (0.790%), decreasing the ß-sheet (0.170%), which led to the accumulation of ROS. In addition, Co. 5h-1 also affected the activity of CYP51, hindered the biosynthesis of ergosterol, and increased cell membrane permeability. Overall, this above research proposed that Co. 5h-1 can be a novel leading structure for development of a fungicide agent.

Analyzing changes in volatile flavor compounds of soy protein isolate during ultrasonic-thermal synergistic treatments using electronic nose and HS-SPME-GC-MS combined with chemometrics.

The beany flavor of soy protein isolate (SPI) creates barriers to their application in food processing. This study investigated the effect of ultrasonic-thermal synergistic treatments, combined with vacuum degassing, on the removal of volatile compounds from SPI. The results revealed that ultrasonic-thermal synergistic treatments altered protein secondary structure and increased fluorescence intensity and surface hydrophobicity, which affected the flavor-binding ability of protein, resulting in reduced electronic nose sensor response values. At synergistic treatment (350 W, 120 ℃ and 150 s), the content of hexanal, (E)-2-hexenal, and 1-octen-3-ol reduced by 70.60 %, 95.60 % and 61.23 %. (E)-2-nonenal and 2-pentylfuran were not detected. Chemometric analysis indicated significant flavor differences between control and treated SPI. Furthermore, α-helix, ß-sheet, ß-turn, and surface hydrophobicity highly correlated with volatile compounds through correlation analysis, indicating that altered protein structure affected interactions with volatile compounds. The study reduced beany flavor and further expanded the range of applications of plant protein in food industry.

Synthesis of Acrylopimaric Acid Triazole Derivatives and Their Antioomycete Activity against Phytophthora capsici.

To develop new antioomycete agents against plant pathogens, two series of acrylopimaric acid triazole derivatives from rosin were synthesized. The in vitro antioomycete activity of these derivatives was evaluated and screened against Pseudoperonospora cubensisi, Plasmopara viticola, Phytophthora sojae, Phytophthora infestans, and Phytophthora capsici. Compound 5m showed the highest antioomycete activity against P. capsici, with a half-maximal effective concentration (EC50) value that was lower than that of the positive control metalaxyl (1.391 and 1.815 mg/L, respectively). Compound 5m demonstrated satisfactory protective and curative efficacy against P. capsici in pepper in in vivo antioomycete activity studies. Physiological and biochemical testing showed that the action mechanism of compound 5m on P. capsici involved altering the morphology and ultrastructure of the mycelium, increasing cell membrane permeability, inducing dysfunction of the nucleus and mitochondria, and ultimately causing cell necrosis. In addition, the analysis of three-dimensional quantitative structure-activity relationship (3D-QSAR) revealed the significance of the molecular structure and charge distribution in the interaction between compound 5m and its target. Collectively, these findings indicate that compound 5m has the potential as an antioomycete candidate.

Effects of acupuncture on sleep quality in patients with Parkinson's disease: A systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate the evidence relating to acupuncture on the sleep quality of patients with Parkinson's disease. DATA SOURCES: Six English-language (PubMed, Cochrane Library, EBSCOhost, Embase, OVID MEDLINE, and Web of Science) and four Chinese-language (China National Knowledge Infrastructure, SinoMed, China Scientific Journals Database, and Wanfang) databases were searched for pertinent studies published from database inception to 11 October 2023. METHODS: Two researchers independently screened eligible studies and extracted relevant data using custom data extraction tables. Methodological quality assessment of the included studies was performed using Cochrane Handbook 5.1.0. Meta-analysis was performed using Cochrane Review Manager version 5.4. RESULTS: Twenty-four studies (1701 participants) met inclusion criteria. The meta-analysis showed that acupuncture improved the Parkinson's Disease Sleep Scale, Pittsburgh Sleep Quality Index, Hamilton Anxiety Scale, Hamilton Depression Scale, Self-Rating Depression Scale, and Parkinson's Disease Questionnaire 39 scores compared with controls (all P < 0.05). CONCLUSION: This review showed that acupuncture improved sleep quality, anxiety and depressive symptoms, and quality of life of patients with Parkinson's disease relative to controls.

Co-delivery of indomethacin and uricase as a new strategy for inflammatory diseases associated with high uric acid.

Uric acid is the final metabolite in humans. High level of uric acid chronically induces urate deposition, aggravates kidney damage, and concomitantly causes an increase in inflammatory factors. Alleviating acute inflammation and decreasing uric acid levels are the key points in the treatment of inflammatory diseases associated with high uric acid. However, a drug delivery system that combines anti-inflammatory and uric acid reduction functions at the same time remains a challenge to be settled. Here, we designed a nanocrystal-based co-delivery platform, IND Nplex, characterized by loading of indomethacin (IND) and uricase. Compared with free IND or uricase, IND Nplex possessed a better anti-inflammatory effect by restraining the release of inflammation-related factors in vitro. In addition, pharmacokinetic and biodistribution studies revealed that IND Nplex significantly prolonged the retention time in vivo and was more concentrated in the kidney. In acute gouty arthritis model rats, IND Nplex markedly relieved ankle joint swelling and mitigated synovial inflammation. In acute kidney injury model rats, IND Nplex indicated better biocompatibility and significant amelioration of renal fibrosis. Moreover, IND Nplex showed the effect of anti-inflammatory and improved renal function via determination of inflammatory factors and biochemical markers in the serum and kidney. In conclusion, these results indicate that IND Nplex exerts anti-inflammatory activity and uric acid-lowering effect and could become a promising candidate for the treatment of uric acid-related diseases.

A flame-retardant and conductive fabric-based triboelectric nanogenerator: Application in fire alarm and emergency evacuation.

The fabrics commonly used in architectural decorative materials pose significant fire hazards due to their flammability and rapid fire spread. Moreover, the traditional fire-alarm systems may fail to function properly in complex fire environments owing to power supply disruptions. In this study, we developed a low-cost and eco-friendly flame-retardant conductive fabric-based triboelectric nanogenerator (FCF-TENG) by integrating flame-retardant conductive nylon fabric and polytetrafluoroethylene soaked cotton fabric. This nanogenerator exhibits excellent flame-retardant properties and remarkable energy-harvesting capabilities. The nylon fabric, treated with layer-by-layer self-assembly method, possesses outstanding self-extinguishing capability and melt-dripping resistance. Additionally, the electrical performance of FCF-TENG significantly improves, with a 10-fold boost in conductivity, and the open-circuit voltage increases by 84% to 92 V. Besides, by incorporating the rectifier circuit, the FCF-TENG is capable of completely charging a 1 µF capacitor within 30 s. Furthermore, the FCF-TENG was successfully applied as a self-powered sensor in the fire-alarm system and served as a safety exit indicator for evacuees and fire rescue. This work presents an effective and innovative application of multifunctional smart textiles for energy harvesting and self-powered sensing.