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Background Central post-stroke pain (CPSP) is an intractable and disabling central neuropathic pain that severely affects patients’ lives, well-being, and socialization abilities. However, CPSP has been poorly studied mechanistically and its treatment remains challenging. Here, we used a rat model of CPSP induced by thalamic hemorrhage to investigate its underlying mechanisms and the effect of stellate ganglion block (SGB) on CPSP and emotional comorbidities. Methods Thalamic hemorrhage was produced by injecting collagenase IV into the ventral-posterolateral nucleus (VPL) of the right thalamus. The up-and-down method with von Frey hairs was used to measure the mechanical allodynia. Behavioral tests were carried out to examine depressive and anxiety-like behaviors including the open field test (OFT), elevated plus maze test (EPMT), novelty-suppressed feeding test (NSFT), and forced swim test (FST). The peri-thalamic lesion tissues were collected for immunofluorescence, western blotting, and enzyme-linked immunosorbent assay (ELISA). Genetic knockdown of thalamic hypoxia-inducible factor-1α (HIF-1α) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) with microinjection of HIF-1α siRNA and NLRP3 siRNA into the VPL of thalamus were performed 3 days before collagenase injection into the same regions. Microinjection of lificiguat (YC-1) and MCC950 into the VPL of thalamus were administrated 30 min before the collagenase injection in order to inhibited HIF-1α and NLRP3 pharmacologically. Repetitive right SGB was performed daily for 5 days and laser speckle contrast imaging (LSCI) was conducted to examine cerebral blood flow. Results Thalamic hemorrhage caused persistent mechanical allodynia and anxiety- and depression-like behaviors. Accompanying the persistent mechanical allodynia, the expression of HIF-1α and NLRP3, as well as the activities of microglia and astrocytes in the peri-thalamic lesion sites, were significantly increased. Genetic knockdown of thalamic HIF-1α and NLRP3 significantly attenuated mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. Further studies revealed that intra-thalamic injection of YC-1, or MCC950 significantly suppressed the activation of microglia and astrocytes, the release of pro-inflammatory cytokines, the upregulation of malondialdehyde (MDA), and the downregulation of superoxide dismutase (SOD), as well as mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. In addition, repetitive ipsilateral SGB significantly restored the upregulated HIF-1α/NLRP3 signaling and the hyperactivated microglia and astrocytes following thalamic hemorrhage. The enhanced expression of pro-inflammatory cytokines and the oxidative stress in the peri-thalamic lesion sites were also reversed by SGB. Moreover, LSCI showed that repetitive SGB significantly increased cerebral blood flow following thalamic hemorrhage. Most strikingly, SGB not only prevented, but also reversed the development of mechanical allodynia and anxiety- and depression-like behaviors induced by thalamic hemorrhage. However, pharmacological activation of thalamic HIF-1α and NLRP3 with specific agonists significantly eliminated the therapeutic effects of SGB on mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. Conclusion This study demonstrated for the first time that SGB could improve CPSP with comorbid anxiety and depression by increasing cerebral blood flow and inhibiting HIF-1α/NLRP3 inflammatory signaling.

Background Accumulating evidence supports that lysine-specific demethylase 5 (KDM5) family members act as oncogenic drivers. This study was performed to elucidate the potential effects of KDM5A on prostate cancer (PCa) progression via the miR-495/YTHDF2/m6A-MOB3B axis. Methods The expression of KDM5A, miR-495, YTHDF2 and MOB3B was validated in human PCa tissues and cell lines. Ectopic expression and knockdown experiments were developed in PCa cells to evaluate their effects on PCa cell proliferation, migration, invasion and apoptosis. Mechanistic insights into the interaction among KDM5A, miR-495, YTHDF2 and MOB3B were obtained after dual luciferase reporter, ChIP, and PAR-CLIP assays. Me-RIP assay was used to determine m6A modification level of MOB3B mRNA in PCa cells. Mouse xenograft models of PCa cells were also established to monitor the tumor growth. Results KDM5A was highly expressed in human PCa tissues and cell lines. Upregulated KDM5A stimulated PCa cell proliferation, migration and invasion, but reduced cell apoptosis. Mechanistically, KDM5A, as a H3K4me3 demethylase, bound to the miR-495 promoter, which led to inhibition of its transcription and expression. As a target of miR-495, YTHDF2 could inhibit MOB3B expression by recognizing m6A modification of MOB3B mRNA and inducing mRNA degradation. Furthermore, KDM5A was found to downregulate MOB3B expression, consequently augmenting PCa cell proliferation, migration and invasion in vitro and promoting tumor growth in vivo via the miR-495/YTHDF2 axis. Conclusion In summary, our study highlights the potential of histone demethylase KDM5A activity in enhancing PCa progression, and suggests KDM5A as a promising target for PCa treatment.

Recently, increasing evidence has suggested the association between gut dysbiosis and Alzheimer’s disease (AD) progression, yet the role of gut microbiota in AD pathogenesis remains obscure. Herein, we provide a potential mechanistic link between gut microbiota dysbiosis and neuroinflammation in AD progression. Using AD mouse models, we discovered that, during AD progression, the alteration of gut microbiota composition leads to the peripheral accumulation of phenylalanine and isoleucine, which stimulates the differentiation and proliferation of pro-inflammatory T helper 1 (Th1) cells. The brain-infiltrated peripheral Th1 immune cells are associated with the M1 microglia activation, contributing to AD-associated neuroinflammation. Importantly, the elevation of phenylalanine and isoleucine concentrations and the increase of Th1 cell frequency in the blood were also observed in two small independent cohorts of patients with mild cognitive impairment (MCI) due to AD. Furthermore, GV-971, a sodium oligomannate that has demonstrated solid and consistent cognition improvement in a phase 3 clinical trial in China, suppresses gut dysbiosis and the associated phenylalanine/isoleucine accumulation, harnesses neuroinflammation and reverses the cognition impairment. Together, our findings highlight the role of gut dysbiosis-promoted neuroinflammation in AD progression and suggest a novel strategy for AD therapy by remodelling the gut microbiota.

Silver( i ) chalcogenide/chalcogenolate clusters are promising photofunctional materials for sensing, optoelectronics and solar energy harvesting applications. However, their instability and poor room-temperature luminescent quantum yields have hampered more extensive study. Here, we graft such clusters to adaptable bridging ligands, enabling their interconnection and the formation of rigid metal–organic frameworks. By controlling the spatial separation and orientation of the clusters, they then exhibit enhanced stability (over one year) and quantum yield (12.1%). Ultrafast dual-function fluorescence switching (<1 s) is also achieved, with turn-off triggered by O 2 and multicoloured turn-on by volatile organic compounds. Single-crystal X-ray diffraction of the inclusion materials, obtained by single-crystal-to-single-crystal transformation, enables precise determination of the position of the small molecules within the framework, elucidating the switching mechanism. The work enriches the cluster-based metal–organic framework portfolio, bridges the gap between silver chalcogenide/chalcogenolate clusters and metal–organic frameworks, and provides a foundation for further development of functional silver-cluster-based materials. The properties of discrete species can sometimes be improved by fixing them into extended materials. This strategy has now been applied to silver( I ) chalcogenide/chalcogenolate clusters, resulting in a metal–organic framework with enhanced stability and fluorescent sensing capabilities. Crystallographic analysis allows precise structural determination of guest binding, which is responsible for both emission turn-off and multicoloured turn-on.

Surgical resection and endoscopic resection comprise two alternative options for the treatment of submucosal tumors (SMTs) originating from the muscularis propria (MP) layer. Endoscopic resection is minimally invasive compared with surgical resection. Conventional non-tunneling techniques, such as endoscopic submucosal dissection (ESD), endoscopic submucosal excavation (ESE), and endoscopic full-thickness resection (EFR) have been demonstrated to be safe and effective. However, these techniques fail to maintain the integrity of the mucosa and induce high risk of perforation, infection, and postoperative strictures. Submucosal tunneling endoscopic resection (STER) is a novel surgical technique that can maintain the integrity of the mucosa by establishing a tunnel between the submucosal and the MP layers. STER has been proven to be effective and safe for the treatment of SMTs. Currently, STER has become a standard treatment for gastrointestinal (GI) SMTs originating from the MP layer, notably in China. In the present review, we describe the indications, procedures, postoperative care, efficacy and safety outcomes, and future perspectives of STER for GI SMTs originating from the MP layer.

The development of facile tailoring approach to adjust the intrinsic activity and stability of atomically-precise metal nanoclusters catalysts is of great interest but remians challenging. Herein, the well-defined Au 8 nanoclusters modified by single-atom sites are rationally synthesized via a co-eletropolymerization strategy, in which uniformly dispersed metal nanocluster and single-atom co-entrenched on the poly-carbazole matrix. Systematic characterization and theoretical modeling reveal that functionalizing single-atoms enable altering the electronic structures of Au 8 clusters, which amplifies their electrocatalytic reduction of CO 2 to CO activity by ~18.07 fold compared to isolated Au 8 metal clusters. The rearrangements of the electronic structure not only strengthen the adsorption of the key intermediates *COOH, but also establish a favorable reaction pathway for the CO 2 reduction reaction. Moreover, this strategy fixing nanoclusters and single-atoms on cross-linked polymer networks efficiently deduce the performance deactivation caused by agglomeration during the catalytic process. This work contribute to explore the intrinsic activity and stability improvement of metal clusters. Tailoring catalytic performance of atomically-precise metal nanoclusters catalysts is of great interest but remains challenging. Here, the authors report a co-eletropolymerization strategy to modify well-defined Au 8 nanoclusters by single-atom sites to enhance its electrocatalytic activity for the reduction of CO 2 towards CO.

The open-circuit demagnetization curve of a hard-magnetic cylinder of length-to-diameter ratio γ measured in a high-field solenoid can be corrected to its corresponding closed-circuit curve using accurately calculated magnetometric demagnetizing factor N m ( γ , χ ) for a paramagnetic cylinder of susceptibility χ , based on a differential paramagnetic approach. The corrected curve can be very close to the curve directly measured using an electromagnet in some cases. However, for grain-oriented cylinders along the easy axis, it has a more rounded knee and a reduced intrinsic coercive force compared to the electromagnet-measured nearly rectangular closed-circuit curve owing to the collective switch of the magnetic moments of grains and the enhanced local demagnetizing fields at the cylinder ends.

Background:Pancreatitis is a common disease of the digestive system. Acute pancreatitis is one of the most common reasons for gastrointestinal hospital admission, and chronic pancreatitis significantly reduces quality of life. However, national epidemiological data on pancreatitis in China are lacking. This study aimed to quantify the disease burden of pancreatitis in China from 1990 to 2019.Methods:This study was based on the Global Burden of Disease Study 2019 dataset. Age-standardized rates of incidence (ASIR), prevalence (ASPR), mortality (ASMR), and disability-adjusted life years (DALYs) were used to describe the disease burden of pancreatitis, and estimated annual percentage change (EAPC) was used to indicate the average change in age-standardized rates. We also described the trend of pancreatitis-related mortality and DALYs, which are attributable to alcohol use by age and sex.Results:From 1990 to 2019, the ASIR, ASPR, ASMR, and age-standardized DALYs of pancreatitis in China decreased by 10.90, 1.50, 0.49, and 15.54 per 100,000, respectively, with EAPCs of −1.35 (95% uncertainty interval [UI]: −1.67, −1.02) and −0.37 (95% UI: −0.43, −0.31), −2.01 (95% UI: −2.07, −1.94) and −2.32 (95% UI: −2.37, −2.28), respectively. Recently, the numbers of incident and prevalent cases have risen, with estimates of 380,018 (95% UI: 308,669–462,767) and 493,765 (95% UI: 416,705–578,675), respectively, in 2019. Among men, the disease burden of pancreatitis was more severe than among women, and with variances in the distribution among different age groups. Age-standardized DALYs caused by alcohol-related pancreatitis have gradually worsened in the past decade, accounting for 34.09% of the total in 2019.Conclusions:The disease burden of pancreatitis in China has declined in the past 30 years, but the exacerbation of population aging poses a challenge to prevention and control of pancreatitis. Alcohol use has gradually become an important factor in the disease burden of pancreatitis in recent years.

Water shortages have become a major problem facing the world today. Membrane separation technology is commonly used in water treatment applications. The development of new materials for water treatment can reduce the energy required for water treatment, reduce cost, and improve efficiency. The unique structure and properties of graphene and silica make them attractive materials for preparation of nanofiltration membranes for water treatment. We have successfully prepared a graphene oxide/silica (GO/SiO2) hybrid composite materials by in situ hydrolysis, using tetraethyl orthosilicate (TEOS) as a silicon source in an alkaline environment. The chemistry and structure of these materials are characterized by TEM, FTIR, Raman, and XPS of GO and the GO/SiO2 composite. BET porosimetry reveals that the total pore volume of the composite is 2.84 cm3 g−1, the specific surface area is 2897 m2 g−1, and the average pore diameter is 3.97 nm. We prepared GO membranes and GO/SiO2 composite membranes by vacuum suction filtration. The morphology of the membrane was observed by FESEM and AFM. The composite membrane has a larger surface roughness (Rms = 9.39). We also tested the thermal stability by TGA, and hydrophilicity by water contact angle measurements. The water permeance of the composite membrane is up to 229.15 L m−2 h−1 bar−1, and the rejection of the rhodamine B dye molecules is as high as 99%. The GO/SiO2 hybrid composite membrane has good hydrophilicity and thermal stability, high water permeance and rejection, and can be developed as a high-performance material for water treatment.

BackgroundRice (Oryza sativa L.) production, such as farmers’ livelihood and the soil quality, has been identified to be strong influenced by climate change in China. However, the benefits of low carbon technologies (LCTs) are still debatable in rice production for farmers, which have been identified to tackle agricultural challenges. The choice of potential LCTs relevant to the case study is based on a literature review of previous empirical studies. Thus, the objectives of the study were to (1) investigate the public perception and preferences of LCTs in rice production of China, and (2) analyze the influences of the factors on farmer’s decision in adopting LCTs in rice production. There were 555 farmer surveys from eight representative rice production counties in HP province of southern China, both the Poisson estimators and multivariate probit (MVP) approach were applied in the study.ResultsOur results show that water-saving irrigation, integrated pest management techniques and planting green manure crops in winter season were the three major LCTs adapted by farmers in rice production. The intensity and probability of LCTs adoptions were influenced by the main factors including farmers’ education level, climate change awareness, machinery ownership, technical support and subsidies. There is a significant correlation among the LCTs, and the adoption of the technologies is interdependent, depicting either complementarities or substitutabilities between the practices.ConclusionsThis study suggests that policies enhance the integration of LCTs would be central to farmers’ knowledge, environmental concerns, technical service and financial support in rice production systems in China.