Efficient molecular conformation generation with quantum-inspired algorithm.

CONTEXT: Conformation generation, also known as molecular unfolding (MU), is a crucial step in structure-based drug design, remaining a challenging combinatorial optimization problem. Quantum annealing (QA) has shown great potential for solving certain combinatorial optimization problems over traditional classical methods such as simulated annealing (SA). However, a recent study showed that a 2000-qubit QA hardware was still unable to outperform SA for the MU problem. Here, we propose the use of quantum-inspired algorithm to solve the MU problem, in order to go beyond traditional SA. We introduce a highly compact phase encoding method which can exponentially reduce the representation space, compared with the previous one-hot encoding method. For benchmarking, we tested this new approach on the public QM9 dataset generated by density functional theory (DFT). The root-mean-square deviation between the conformation determined by our approach and DFT is negligible (less than about 0.5Å), which underpins the validity of our approach. Furthermore, the median time-to-target metric can be reduced by a factor of five compared to SA. Additionally, we demonstrate a simulation experiment by MindQuantum using quantum approximate optimization algorithm (QAOA) to reach optimal results. These results indicate that quantum-inspired algorithms can be applied to solve practical problems even before quantum hardware becomes mature. METHODS: The objective function of MU is defined as the sum of all internal distances between atoms in the molecule, which is a high-order unconstrained binary optimization (HUBO) problem. The degree of freedom of variables is discretized and encoded with binary variables by the phase encoding method. We employ the quantum-inspired simulated bifurcation algorithm for optimization. The public QM9 dataset is generated by DFT. The simulation experiment of quantum computation is implemented by MindQuantum using QAOA.

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.

Dexmedetomidine attenuates ferroptosis by Keap1-Nrf2/HO-1 pathway in LPS-induced acute kidney injury.

Previous research has demonstrated that Dexmedetomidine (DEX), an α2 adrenergic agonist commonly used for its sedative and analgesic properties, can attenuate lipopolysaccharide (LPS)-induced acute kidney injury (AKI). This study explores the possibility that DEX's protective effects in LPS-induced AKI are mediated through the inhibition of ferroptosis, a form of regulated cell death characterized by iron-dependent lipid peroxidation, and the activation of the antioxidant response through the Keap1/Nrf2/HO-1 signaling pathway. We induced AKI in 42 mice using LPS and divided them into six groups: saline control, LPS, LPS + DEX, LPS + Ferrostatin-1 (LPS + Fer-1; a ferroptosis inhibitor), LPS + DEX with α2-receptor antagonist Altipamizole (LPS + DEX + ATI), and LPS + DEX with Nrf2 inhibitor ML385 (LPS + DEX + ML385). After 24 h, we analyzed blood and kidney tissues. LPS exposure resulted in AKI, with increased serum creatinine, BUN, and cystatin C, and tubular damage, which DEX and Fer-1 ameliorated. However, Altipamizole and ML385 negated these improvements. The LPS group exhibited elevated oxidative stress markers and mitochondrial damage, reduced by DEX and Fer-1, but not when α2-adrenergic or Nrf2 pathways were blocked. Nrf2 and HO-1 expression declined in the LPS group, rebounded with LPS + DEX and LPS + Fer-1, and fell again with inhibitors; inversely, Keap1 expression varied. Our results demonstrate that DEX may protect against LPS-induced AKI, at least partially by regulating ferroptosis and the α2-adrenergic receptor/Keap1/Nrf2/HO-1 pathway, suggesting a potential therapeutic role for DEX in AKI management by modulating cell death and antioxidant defenses.

Biochemical targets of the micropeptides encoded by lncRNAs.

Long non-coding RNAs (lncRNAs) are a group of transcripts longer than 200 nucleotides, which play important roles in regulating various cellular activities by the action of the RNA itself. However, about 40% of lncRNAs in human cells are potentially translated into micropeptides (also referred to as microproteins) usually shorter than 100 amino acids. Thus, these lncRNAs may function by both RNAs directly and their encoded micropeptides. The micropeptides encoded by lncRNAs may regulate transcription, translation, protein phosphorylation or degradation, or subcellular membrane functions. This review attempts to summarize the biochemical targets of the micropeptides-encoded by lncRNAs, which function by both RNAs and micropeptides, and discuss their associations with various diseases and their potentials as drug targets.

The role of FERMT2 in the tumor microenvironment and immunotherapy in pan-cancer using comprehensive single-cell and bulk sequencing.

FERMT2 has been identified as a participant in integrin-linked kinase signaling pathways, influencing epithelial-mesenchymal transition and thereby affecting tumor initiation, progression, and invasion. While the character of FERMT2 in the tumor microenvironment (TME) as well as its implications for immunotherapy remain unclear. Thus, we conducted a comprehensive analysis to assess the prognostic significance of FERMT2 using Kaplan-Meier analysis. In addition, we employed enrichment analysis to uncover potential underlying molecular mechanisms. Using "Immunedeconv" package, we evaluated the immune characteristics of FERMT2 within TME. Furthermore, we determined the expression levels of FERMT2 in various cell types within TME, based on single-cell sequencing data. To confirm the co-expression of FERMT2 and markers of cancer-associated fibroblasts (CAFs), we performed multiplex immunofluorescence staining on tissue paraffin sections across various cancer types. Our analysis disclosed a significant correlation between elevated FERMT2 expression and unfavorable prognosis in specific cancer types. Furthermore, we identified a strong correlation between FERMT2 expression and diverse immune-related factors, including immune checkpoint molecules, immune cell infiltration, microsatellite instability (MSI), and tumor mutational burden (TMB). Additionally, there was a significant correlation between FERMT2 expression and immune-related pathways, particularly those associated with activating, migrating, and promoting the growth of fibroblasts in diverse cancer types. Interestingly, we observed consistent co-expression of FERMT2 in both malignant tumor cells and stromal cells, particularly within CAFs. Notably, our findings also indicated that FERMT2, in particular, exhibited elevated expression levels within tumor tissues and co-expressed with α-SMA in CAFs based on the multiplex immunofluorescence staining results.

Case of submandibular schwannoma and review of literature.

Schwannomas are slow growing, benign tumours arising from Schwann cells. They are usually solitary and are sometimes associated with Neurofibromatosis type 1 and 2. As reported by Okada et al., while approximately 25%-40% of extra-cranial schwannomas occur in the head and neck region, Schwannomas of the oral cavity are very uncommon, accounting for only 1% of all Schwannomas. We report a case of a sublingual schwannoma in a 47-year-old female, discovered incidentally during the workup for tinnitus. The radiological and histopathological findings, along with a literature review, are presented.

Peimenine unleashes therapeutic promise in urothelial bladder cancer: inhibition of proliferation, induction of cell death and modulation of key pathways.

Peimenine (PEI) is a steroid alkaloid substance isolated from Fritillaria thunbergii bulbs. It has various pharmacological activities, such as relief from coughs and asthma, expectorant properties, antibacterial effects, sedative qualities, and anti-inflammatory properties. Notably, PEI can effectively inhibit the proliferation and tumor formation of liver cancer and osteosarcoma cells by inducing autophagic cell death. However, the precise effect and mechanisms of PEI on urothelial bladder cancer (UBC) cells remain uncertain. Thus, this study aims to investigate the impact of PEI on UBC cells both in vivo and in vitro. The IC50 values of BIU-87 and EJ-1 cells after 48 h were 710.3 and 651.1 µg/mL, respectively. Additionally, PEI blocked the cell cycle in BIU-87 and EJ-1 cells during the G1 phase. Furthermore, it hindered the migration of BIU-87 and EJ-1 cells substantially. PEI significantly inhibited the tumor development of EJ-1 cells within the xenograft tumor model in vivo. Mechanically, PEI augmented the protein and mRNA expression of BIM, BAK1, and Cytochrome C (CYCS) in UBC cells. Taken together, PEI suppressed the proliferation of UBC cells both in vitro and in vivo by inducing cell death and cell cycle arrest, suggesting that PEI could be applied in the treatment of UBC.

Parenting beliefs and practices as precursors to academic outcomes in Chinese children.

Due to the rapid sociocultural changes in China, Chinese parents' childrearing beliefs and practices have undergone dramatic transformations. Against this context, this study examined whether Chinese parents' endorsement of progressive and traditional childrearing beliefs would predict children's academic achievement, as well as whether parenting practices would mediate this association. This study utilized a longitudinal design and followed 206 Chinese families for 2 years from the end of preschool to Grade 2. Parents showed greater endorsement of progressive than traditional childrearing beliefs, as well as higher use of authoritative than authoritarian parenting practices. Parents' childrearing beliefs in preschool predicted children's math achievement in Grade 2 via authoritative parenting. However, parenting beliefs were unrelated to authoritarian parenting, and authoritarian parenting did not predict any of the child academic outcomes in Grade 2. The findings suggest Chinese parents' orientations toward progressive parenting beliefs and authoritative parenting practices. They also highlight the utility of parenting beliefs in explaining disparities in early academic achievement. The nonsignificant findings pertinent to authoritarian parenting call for re-examination of the cultural meaning and effects of authoritarian parenting in Chinese society.

[Pathogenesis of ferroptosis on chronic kidney disease and traditional Chinese medicine intervention: a review].

Chronic kidney disease(CKD) is an insidious disease that has become a significant global public health issue due to its high incidence rate, low awareness, low diagnostic rate, poor prognosis, and high medical costs. Recent studies have shown that CKD development is associated with varying degrees of ferroptosis features. Traditional Chinese medicine(TCM) can regulate iron metabolism, lipid peroxidation, antioxidant systems to inhibit ferroptosis and delay the progression of CKD. Consequently, the intervention mechanism of ferroptosis has become one of the focuses of CKD research. TCM has thousands of years of traditional experience and wisdom. It focuses on the overall regulation of human body functions and can stimulate the body's disease resistance and recovery capabilities, which has certain advantages in treating CKD. However, there is currently a lack of comprehensive articles on the application of TCM in intervening ferroptosis to treat CKD and the pathogenesis of ferroptosis in CKD. Therefore, this article summarizes the latest research progress both domestically and internationally, briefly introduces the main mechanisms of ferroptosis, and systematically reviews the relationship between ferroptosis and CKD. The article integrates TCM theories related to ferroptosis in CKD, including "deficiency" "stasis" "phlegm turbidity" and "toxins" and summarizes the research status of active ingredients and herbal formulas in intervening ferroptosis to treat CKD. By considering ferroptosis from a new perspective, this article aims to provide new targets and directions for the application of TCM in treating CKD.

High keratin 15 expression reflects favorable prognosis in early cervical cancer patients.

OBJECTIVE: Keratin 15 (KRT15) exhibits inconsistent prognostic roles in different cancers, and its prognostic value in early cervical cancer patients who receive tumor resection remains unknown. This study aimed to assess the relationship of KRT15 expression with prognosis in these patients. METHODS: Totally, 147 early cervical cancer patients who received tumor resection were reviewed in this retrospective study. KRT15 was detected in formalin-fixed paraffin-embedded tumor tissue by immunohistochemistry (IHC). KRT15 IHC scores were computed by multiplying the percentage of positively stained cells (scored as 0-4) and corresponding staining intensity (scored as 0-3), ranging from 0 to 12. RESULTS: Elevated KRT15 IHC score was linked with moderate to well differentiation (P = 0.005), tumor size ≤ 4 cm (P = 0.017), and International Federation of Gynecology and Obstetrics (FIGO) stage Ia/Ib (P < 0.001). KRT15 IHC score was inversely associated with adjuvant radiotherapy (P = 0.025) and adjuvant chemotherapy (P = 0.016). KRT15 IHC score ≥ 1 was linked with increased disease-free survival (DFS) (P = 0.003) and overall survival (OS) (P = 0.049). Meanwhile, KRT15 IHC score ≥ 1 independently predicted increased DFS (hazard ratio = 0.213, P = 0.017), but not OS (P > 0.05). KRT15 IHC score ≥ 3 and KRT15 IHC score ≥ 6 could not predict DFS or OS (all P > 0.05). By subgroup analyses, KRT15 IHC score ≥ 1 forecasted favorable DFS in patients with age > 45 years, human papillomavirus-positive, squamous carcinoma, and tumor size ≤ 4 cm (all P < 0.05). KRT15 IHC score ≥ 1 and KRT15 IHC score ≥ 3 predicted ascended DFS in patients without adjuvant radiotherapy or adjuvant chemotherapy (all P < 0.05). CONCLUSION: High KRT15 expression reflects favorable tumor features and longer survival in early cervical cancer patients who receive tumor resection.

[Spatial-temporal Variation in Water Quality of Rain-source Rivers in Shenzhen from 2015 to 2021 and Its Response to Rainfall].

Rain-source urban rivers have the characteristics of small water capacity， lack of dynamic water supply， and being easily polluted. This study analyzed the spatial and temporal distribution characteristics of river water quality and the response of characteristic pollutants to rainfall based on daily rainfall data and 21 water quality indicators of nine major river basins in Shenzhen （excluding Shenzhen-Shantou） from 2015 to 2021 by using the single-factor assessment method， comprehensive pollution index method， hierarchical cluster analysis， and Pearson correlation. The results showed that： ① in 2015， the water quality of most sections in the whole region was inferior Class V water. After October 2018， the overall water quality of rivers was greatly improved， which was consistent with the background of Shenzhen's special water control activities in 2018. By 2021， the water quality of approximately 62% of sections reached Class Ⅰ-Ⅲ water standards. ② The water pollution in the densely populated western part of Shenzhen was more serious than that in the eastern part， and the water pollution in the lower reaches of the estuaries and tributaries was more serious than that in the upper reaches. ③ The water quality of the Pingshan River， Guanlan River， Longgang River， and Maozhou River was significantly affected by rainfall. ④ The main characteristic pollution indexes of the Shenzhen River were DO， permanganate index， COD， BOD5， NH4+-N， TP， petroleum， and anionic surfactant. For the Pingshan River and Longgang River， rainfall increased the concentrations of TP and NH4+-N. For the Maozhou River， rainfall increased the concentrations of TP and COD. For the Shenzhen River， rainfall increased the concentrations of COD， TP， and NH4+-N. The above results reveal the spatio-temporal variation in rain-source river water quality in Shenzhen and its response to non-point source pollution caused by rainfall events and provide a scientific reference for building a higher quality water environment in Shenzhen.

Medicarpin suppresses lung cancer cell growth in vitro and in vivo by inducing cell apoptosis.

Lung cancer (LC) is the leading cause of cancer deaths worldwide. Surgery, chemoradiotherapy, targeted therapy, and immunotherapy are considered dominant treatment strategies for LC in the clinic. However, drug resistance and meta-stasis are two major challenges in cancer therapies. Medicarpin (MED) is an isoflavone compound isolated from alfalfa, which is usually used in traditional medicine. This study was de sig ned to evaluate the anti-LC effect and reveal the underlying mechanisms of MED in vivo and in vitro. We found that MED could significantly inhibit proliferation, induce apoptosis, and cell cycle arrest of A549 and H157 cell lines. Basically, MED induced cell apoptosis of LC cells by upregu lating the expression of pro-apoptotic proteins BAX and Bak1, leading to the cleavage of caspase-3 (Casp3). Moreover, MED inhibited the proliferation of LC cells via downregulating the expression of proliferative protein Bid. Overall, MED inhibited LC cell growth in vitro and in vivo via suppressing cell proliferation and inducing cell apoptosis, suggesting the therapeutic potential of MED in treating LC.

Gut microbiota and its metabolic products in acute respiratory distress syndrome.

The prevalence rate of acute respiratory distress syndrome (ARDS) is estimated at approximately 10% in critically ill patients worldwide, with the mortality rate ranging from 17% to 39%. Currently, ARDS mortality is usually higher in patients with COVID-19, giving another challenge for ARDS treatment. However, the treatment efficacy for ARDS is far from satisfactory. The relationship between the gut microbiota and ARDS has been substantiated by relevant scientific studies. ARDS not only changes the distribution of gut microbiota, but also influences intestinal mucosal barrier through the alteration of gut microbiota. The modulation of gut microbiota can impact the onset and progression of ARDS by triggering dysfunctions in inflammatory response and immune cells, oxidative stress, cell apoptosis, autophagy, pyroptosis, and ferroptosis mechanisms. Meanwhile, ARDS may also influence the distribution of metabolic products of gut microbiota. In this review, we focus on the impact of ARDS on gut microbiota and how the alteration of gut microbiota further influences the immune function, cellular functions and related signaling pathways during ARDS. The roles of gut microbiota-derived metabolites in the development and occurrence of ARDS are also discussed.

Alfalfa MsbHLH115 confers tolerance to cadmium stress through activating the iron deficiency response in Arabidopsis thaliana.

Cadmium (Cd) pollution severely affects plant growth and development, posing risks to human health throughout the food chain. Improved iron (Fe) nutrients could mitigate Cd toxicity in plants, but the regulatory network involving Cd and Fe interplay remains unresolved. Here, a transcription factor gene of alfalfa, MsbHLH115 was verified to respond to iron deficiency and Cd stress. Overexpression of MsbHLH115 enhanced tolerance to Cd stress, showing better growth and less ROS accumulation in Arabidopsis thaliana. Overexpression of MsbHLH115 significantly enhanced Fe and Zn accumulation and did not affect Cd, Mn, and Cu concentration in Arabidopsis. Further investigations revealed that MsbHLH115 up-regulated iron homeostasis regulation genes, ROS-related genes, and metal chelation and detoxification genes, contributing to attenuating Cd toxicity. Y1H, EMSA, and LUC assays confirmed the physical interaction between MsbHLH115 and E-box, which is present in the promoter regions of most of the above-mentioned iron homeostasis regulatory genes. The transient expression experiment showed that MsbHLH115 interacted with MsbHLH121pro. The results suggest that MsbHLH115 may directly regulate the iron-deficiency response system and indirectly regulate the metal detoxification response mechanism, thereby enhancing plant Cd tolerance. In summary, enhancing iron accumulation through transcription factor regulation holds promise for improving plant tolerance to Cd toxicity, and MsbHLH115 is a potential candidate for addressing Cd toxicity issues.

Efficacy and Safety of Different Doses of Rivaroxaban and Risk Factors for Bleeding in Elderly Patients with Venous Thromboembolism: A Real-World, Multicenter, Observational, Cohort Study.

INTRODUCTION: Venous thromboembolism (VTE) consists of deep vein thrombosis (DVT) and pulmonary embolism (PE). Rivaroxaban is a direct oral anticoagulant (DOAC) inhibiting activated coagulation factor X (FXa), and exerts several advantages in the treatment of VTE compared to conventional therapy. However, the efficacy and safety of rivaroxaban in elderly patients with VTE was still poorly understood. METHODS: The study was carried out using an observational and non-interventional approach. A total of 576 patients aged ≥ 60 years with newly diagnosed VTE were included in the study. All patients received rivaroxaban with recommended treatment duration of ≥ 3 months for secondary prevention. In addition, 535 elderly patients with various diseases except VTE were included in the study in a retrospective and randomized way. RESULTS: The total bleeding rate was 12.2% (70/576). Major bleeding and non-major clinically relevant (NMCR) bleeding occurred in 4 (0.69%) patients and 5 (0.87%) patients, respectively. The rate of recurrent VTE was 5.4%. The mean level of D-dimers was increased by 467.2% in the elderly patients with VTE compared with the elderly patients without VTE. The elderly patients with VTE receiving rivaroxaban at a dose of 10 mg once daily (n = 134) had lower risk for bleeding (3.7% vs 14.7%; P = 0.001) and a similar rate of recurrent VTE (4.5% vs 5.7%; P = 0.596) as compared to the elderly patients with VTE receiving rivaroxaban at higher doses including 15 mg once daily and 20 mg once daily (n = 442). In addition, age, concomitant aspirin, hemoglobin, activated partial thromboplastin time (APTT), and rivaroxaban doses were independent predictive factors for bleeding events. CONCLUSIONS: The study suggested that a dose of 10 mg once daily should be the priority in elderly patients with VTE receiving long-term rivaroxaban anticoagulation therapy in view of reduced bleeding risk.

Single Idiosyncratic Ionic Generator Working in Iso-Osmotic Solutions Via Ligand Confined Assembled in Gaps Between Nanosheets.

Numerous reported bioinspired osmotic energy conversion systems employing cation-/anion-selective membranes and solutions with different salinity are actually far from the biological counterpart. The iso-osmotic power generator with the specific ionic permselective channels (e.g., K+ or Na+ channels) which just allow specific ions to get across and iso-osmotic solutions still remain challenges. Inspired by nature, we report a bioinspired K+ -channel by employing a K+ selective ligand, 1,1,1-tris{[(2'-benzylaminoformyl)phenoxy]methyl}ethane (BMP) and graphene oxide membrane. Specifically, the K+ and Na+ selectivity of the prepared system could reach up to ≈17.8, and the molecular dynamics simulation revealed that the excellent permselectivity of K+ mainly stemmed from the formed suitable channel size. Thus, we assembled the K+ -selective iso-osmotic power generator (KSIPG) with the power density up to ≈15.1 mW/m2 between equal concentration solutions, which is higher than traditional charge-selective osmotic power generator (CSOPG). The proposed strategy has well shown the realizable approach to construct single-ion selective channels-based highly efficient iso-osmotic energy conversion systems and would surely inspire new applications in other fields, including self-powered systems and medical materials, etc.

Effect of hip strategy-based motion control training on walking function restoration after ankle joint injury.

OBJECTIVES: The study aimed to explore the effect of hip strategybased motion control training on the recovery of walking function after ankle injury and the optimization of the rehabilitation program. PATIENTS AND METHODS: In the study, 62 patients with ankle injuries were randomly divided into the observation group (n=30; 24 males, 6 females; mean age: 41.9±8.5 years; range, 28 to 56 years) and the control group (n=32; 26 males, 6 females; mean age: 42.0±9.3 years; range, 27 to 55 years) between September 2021 and September 2022. Both groups were treated using routine rehabilitation training, including conventional drug and rehabilitation treatment. The observation group additionally received hip strategy-based motion control training, which included hip muscle strength training, hip joint stability control training, balance testing and training system training, and three-dimensional gait analysis system training for six weeks. All patients were evaluated before and after the treatment using the balance function parameters (motion length and motion ellipse area), Berg Balance Scale, the timed up-and-go test, and three-dimensional gait analysis system (step length and step frequency). RESULTS: There was no significant difference in the evaluation indexes between the two groups before treatment (p>0.05). After treatment, the evaluation indexes of the two groups were significantly better than those before treatment (p<0.05), and all the indexes in the observation group were significantly better than those in the control group (p<0.05). CONCLUSION: Hip strategy-based motion control training could significantly improve the recovery of walking function in patients with ankle injuries.

Anti-epileptic and Neuroprotective Effects of Ultra-low Dose NADPH Oxidase Inhibitor Dextromethorphan on Kainic Acid-induced Chronic Temporal Lobe Epilepsy in Rats.

Neuroinflammation mediated by microglia and oxidative stress play pivotal roles in the development of chronic temporal lobe epilepsy (TLE). We postulated that kainic acid (KA)-Induced status epilepticus triggers microglia-dependent inflammation, leading to neuronal damage, a lowered seizure threshold, and the emergence of spontaneous recurrent seizures (SRS). Extensive evidence from our laboratory suggests that dextromethorphan (DM), even in ultra-low doses, has anti-inflammatory and neuroprotective effects in many animal models of neurodegenerative disease. Our results showed that administration of DM (10 ng/kg per day; subcutaneously via osmotic minipump for 4 weeks) significantly mitigated the residual effects of KA, including the frequency of SRS and seizure susceptibility. In addition, DM-treated rats showed improved cognitive function and reduced hippocampal neuronal loss. We found suppressed microglial activation-mediated neuroinflammation and decreased expression of hippocampal gp91phox and p47phox proteins in KA-induced chronic TLE rats. Notably, even after discontinuation of DM treatment, ultra-low doses of DM continued to confer long-term anti-seizure and neuroprotective effects, which were attributed to the inhibition of microglial NADPH oxidase 2 as revealed by mechanistic studies.

The Health Insurance Fund Participates in Controlling the Epidemic: Insights from German Experience in Dealing with the COVID-19 Pandemic.

To reveal the importance of the participation of the health insurance fund in the prevention and control of serious infectious diseases, this research retrospectively analyzed the case of the German statutory health insurance fund in response to the COVID-19 epidemic. Based on Germany's practical experience, this research offers a strategy idea for other countries with a social health insurance system, aiming to ensure that the health care system does not collapse rapidly due to medical resource shortage in the event of a pandemic. Firstly, this research conducted a documentary analysis to systematically collate the temporary and additional coverage measures provided by the health insurance fund from January to the end of July 2020, which sheds light on the pivotal role of these funds in epidemic prevention and control. Secondly, this research used comparative analysis to examine the time sequence of implementing these different types of coverage measures in the progression of the epidemic to illustrate how the health insurance fund adjusted its response measures. The health insurance fund was actively involved in the development of core strategies for combating the epidemic when it broke out, by taking part in joint multisectoral consultations. By using payment instruments flexibly, the fund led the implementation of epidemic prevention and control measures, as it could allocate health resources quickly and efficiently in emergencies. Furthermore, the health insurance fund played a critical role in transmitting information on the epidemic and guiding the insured to take appropriate protective measures. By fulfilling its role in health promotion, particularly in the area of health education, the fund provided important complementary and synergistic contributions to the prevention and control of the spread of infectious diseases. In summary, this research provides a new model for other countries for mobilizing a multi-sectoral response to infectious disease prevention and control, and emphasises the key role of the health insurance fund in responding to major public health crises.

Mechanism and Association between Microbial Nitrogen Transformation in Rhizosphere and Accumulation of Ciprofloxacin in Choysum (Brassica parachinensis).

Rhizosphere microbiota are an important factor impacting plant uptake of pollutants. However, little is known about how microbial nitrogen (N) transformation in the rhizosphere affects the uptake and accumulation of antibiotics in plants. Here, we determined recruitment of N transformation functional bacteria upon ciprofloxacin (CIP) exposure, by comparing differences in assembly processes of both rhizospheric bacterial communities and N transformation between two choysum (Brassica parachinensis) varieties differing in CIP accumulation. The low accumulation variety (LAV) of CIP recruited more host bacteria (e.g., Nitrospiria and Nitrolancea) carrying nitrification genes (mainly nxrA) but fewer host bacteria carrying denitrification genes, especially narG, relative to the high accumulation variety (HAV) of CIP. The nxrA and narG abundance in the LAV rhizosphere were, respectively, 1.6-7.8 fold higher and 1.4-3.4 fold lower than those in the HAV rhizosphere. Considering that nitrate can decrease CIP uptake into choysum through competing for the proton motive force and energy, such specific bacteria recruitment in LAV favored the production and utilization of nitrate in its rhizosphere, thus limiting its CIP accumulation with 1.6-2.4 fold lower than the HAV. The findings give insight into the mechanism underlying low pollutant accumulation, filling the knowledge gap regarding the profound effects of rhizosphere microflora and N transformation processes on antibiotic accumulation in crops.