The neuronal implementation of representational geometry in primate prefrontal cortex.

Modern neuroscience has seen the rise of a population-doctrine that represents cognitive variables using geometrical structures in activity space. Representational geometry does not, however, account for how individual neurons implement these representations. Leveraging the principle of sparse coding, we present a framework to dissect representational geometry into biologically interpretable components that retain links to single neurons. Applied to extracellular recordings from the primate prefrontal cortex in a working memory task with interference, the identified components revealed disentangled and sequential memory representations including the recovery of memory content after distraction, signals hidden to conventional analyses. Each component was contributed by small subpopulations of neurons with distinct spiking properties and response dynamics. Modeling showed that such sparse implementations are supported by recurrently connected circuits as in prefrontal cortex. The perspective of neuronal implementation links representational geometries to their cellular constituents, providing mechanistic insights into how neural systems encode and process information.

Highly asymmetric aldol reaction of isatins and ketones catalyzed by chiral bifunctional primary-amine organocatalyst on water.

Herein, we have reported an environmentally friendly asymmetric aldol reaction between isatins and ketones catalyzed by double-hydrogen-bonded primary amine organocatalysts on water under mild conditions. Enantioenriched 3-hydroxy-2-oxindoles were obtained in high yields (up to 99%) and excellent stereoselectivities (up to 99 : 1 dr and 99% ee) under optimal conditions. Furthermore, the model reaction involving isatin and cyclohexanone was successfully scaled to 10 mmol with no reduction in yield or stereoselectivity. In addition, the catalyst was recovered via simple filtration and was subsequently reused on water, which highlights its good application potential.

Synthesis of A11Cys-B11Cys Disulfide Surrogates of H2 Relaxin through an Intermolecular Native Chemical Ligation-Assisted Diaminodiacid Strategy.

We report an intermolecular native chemical ligation-assisted diaminodiacid strategy for the flexible construction of A11Cys-B11Cys disulfide surrogates of H2 relaxin. The practicality of this strategy was evidenced by the synthesis of four new H2 relaxin analogs, among which H2-2a-B28Ile is found to exhibit improved potency, selectivity, and stability compared with native H2 relaxin.

The role of glucocorticoids in increasing cardiovascular risk.

Introduction: Different studies provide conflicting evidence regarding the potential for glucocorticoids (GCs) to increase the risk of cardiovascular diseases. This study performed a systematic review and meta-analysis to determine the correlation between GCs and cardiovascular risk, including major adverse cardiovascular events (MACE), death from any cause, coronary heart disease (CHD), heart failure (HF), and stroke. Methods: We performed a comprehensive search in PubMed and Embase (from inception to June 1, 2022). Studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the associations of interest were included. Results: A total of 43 studies with 15,572,512 subjects were included. Patients taking GCs had a higher risk of MACE (RR = 1.27, 95% CI: 1.15-1.40), CHD (RR = 1.25, 95% CI: 1.11-1.41), and HF (RR = 1.92, 95% CI: 1.51-2.45). The MACE risk increased by 10% (95% CI: 6%-15%) for each additional gram of GCs cumulative dose or by 63% (95% CI: 46%-83%) for an additional 10 µg daily dose. The subgroup analysis suggested that not inhaled GCs and current GCs use were associated with increasing MACE risk. Similarly, GCs were linked to an increase in absolute MACE risk of 13.94 (95% CI: 10.29-17.58) cases per 1,000 person-years. Conclusions: Administration of GCs is possibly related with increased risk for MACE, CHD, and HF but not increased all-cause death or stroke. Furthermore, it seems that the risk of MACE increased with increasing cumulative or daily dose of GCs.

Panaxynol ameliorates cardiac ischemia/reperfusion injury by suppressing NLRP3-induced pyroptosis and apoptosis via HMGB1/TLR4/NF-κB axis.

BACKGROUND AND PURPOSE: Panaxynol (PNN) is a common natural minor component in Umbelliferae plants. Many clinical studies have shown that PNN exhibits nutritional value and anti-inflammatory and other pharmacological activities. However, whether PNN can mediate cardiac ischemia/reperfusion injury (IRI) remains unclear. Here, we aimed to determine the potential effects of PNN on myocardial IRI. METHODS: Myocardial IRI was stimulated in a mouse IRI model, and neonatal rat ventricle myocytes (NRVMs) were exposed to hypoxia/reoxygenation to construct in an vitro model. Myocardial infarction size, myocardial tissue injury, myocardial apoptotic index, hemodynamic monitoring, pyroptosis-related proteins, cardiac enzyme activities and inflammatory responses were examined to assess myocardial injury. RESULTS: It was found that PNN administration markedly reduced myocardial infarct size and apoptosis, suppressed myocardial damage and cell pyroptosis, attenuated pro-inflammatory cytokines and neutrophil infiltration via NLRP3 inhibitor. More importantly, PNN treatment remarkably decreased the expression of TLR4/NF-κB pathway-associated proteins and NLRP3-related pyroptosis proteins by HMGB1 inhibitor. PNN also enhanced cell viability, reduced cardiac enzyme activities, suppressed apoptosis and attenuated inflammation in the isolated NRVMs. Furthermore, vitro studies indicated that MCC950 (a NLRP3 inhibitor) increased the anti-inflammatory and anti-apoptotic effects of PNN on NRVMs via HMGB1/TLR4 pathway. CONCLUSION: To sum up, our results demonstrate that PNN exhibits a cardioprotective effect by modulating heart IRI-induced apoptosis and pyroptosis via HMGB1/TLR4/NF-κB pathway, thereby inhibiting NLRP3 inflammasome stimulation.

Human acute microelectrode array recordings with broad cortical access, single-unit resolution, and parallel behavioral monitoring.

There are vast gaps in our understanding of the organization and operation of the human nervous system at the level of individual neurons and their networks. Here, we report reliable and robust acute multichannel recordings using planar microelectrode arrays (MEAs) implanted intracortically in awake brain surgery with open craniotomies that grant access to large parts of the cortical hemisphere. We obtained high-quality extracellular neuronal activity at the microcircuit, local field potential level and at the cellular, single-unit level. Recording from the parietal association cortex, a region rarely explored in human single-unit studies, we demonstrate applications on these complementary spatial scales and describe traveling waves of oscillatory activity as well as single-neuron and neuronal population responses during numerical cognition, including operations with uniquely human number symbols. Intraoperative MEA recordings are practicable and can be scaled up to explore cellular and microcircuit mechanisms of a wide range of human brain functions.

Single-Shot Solid-Phase Synthesis of Full-Length H2 Relaxin Disulfide Surrogates.

Chemical synthesis of insulin superfamily proteins (ISPs) has recently been widely studied to develop next-generation drugs. Separate synthesis of multiple peptide fragments and tedious chain-to-chain folding are usually encountered in these studies, limiting accessibility to ISP derivatives. Here we report the finding that insulin superfamily proteins (e.g. H2 relaxin, insulin itself, and H3 relaxin) incorporating a pre-made diaminodiacid bridge at A-B chain terminal disulfide can be easily and rapidly synthesized by a single-shot automated solid-phase synthesis and expedient one-step folding. Our new H2 relaxin analogues exhibit almost identical structures and activities when compared to their natural counterparts. This new synthetic strategy will expediate production of new ISP analogues for pharmaceutical studies.

Bioinformatics analysis of ferroptosis in spinal cord injury.

Ferroptosis plays a key role in aggravating the progression of spinal cord injury (SCI), but the specific mechanism remains unknown. In this study, we constructed a rat model of T10 SCI using a modified Allen method. We identified 48, 44, and 27 ferroptosis genes that were differentially expressed at 1, 3, and 7 days after SCI induction. Compared with the sham group and other SCI subgroups, the subgroup at 1 day after SCI showed increased expression of the ferroptosis marker acyl-CoA synthetase long-chain family member 4 and the oxidative stress marker malondialdehyde in the injured spinal cord while glutathione in the injured spinal cord was lower. These findings with our bioinformatics results suggested that 1 day after SCI was the important period of ferroptosis progression. Bioinformatics analysis identified the following top ten hub ferroptosis genes in the subgroup at 1 day after SCI: STAT3, JUN, TLR4, ATF3, HMOX1, MAPK1, MAPK9, PTGS2, VEGFA, and RELA. Real-time polymerase chain reaction on rat spinal cord tissue confirmed that STAT3, JUN, TLR4, ATF3, HMOX1, PTGS2, and RELA mRNA levels were up-regulated and VEGFA, MAPK1 and MAPK9 mRNA levels were down-regulated. Ten potential compounds were predicted using the DSigDB database as potential drugs or molecules targeting ferroptosis to repair SCI. We also constructed a ferroptosis-related mRNA-miRNA-lncRNA network in SCI that included 66 lncRNAs, 10 miRNAs, and 12 genes. Our results help further the understanding of the mechanism underlying ferroptosis in SCI.

Research on ability of tetramethylpyrazine on promoting neurogenesis after OGD injury based on neural stem cell microenvironment / 中国药理学通报

Aim To study the ability of tetramethylpyrazine (TMP) on promoting neurogenesis in neural stem cell microenvironment after oxygen-glucose deprivation (OGD) injury in vitro. Methods Neural stem cells (NSCs), astrocytes (ACs) and cerebral microvascular endothelial cells (BMECs) were respectively extracted and separated to establish a co-culture system. The OGD modeling conditions were optimized by NSCs activity, and the concentration of TMP was optimized by Nissl staining. Then CCK-8 and Nestin

Antioxidant, AChE inhibitory, and anticancer effects of Verbascum thapsus extract.

Verbascum thapsus (VT) is a medicinal plant that is used in folk medicine to treat a variety of ailments. For this study, the biological functions of VT methanol extract were determined in vitro. The plant's methanol extract was created through the maceration process. The phytochemical composition of plant extracts was investigated using liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). The antioxidant capacity of the extract was determined using the DPPH (2,2-diphenyl-1-picrylhydrazil) and ABTS (2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) tests and its cytotoxicity was assessed using the MTT ((3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a tetrazole)) assay on the Caco-2 (human colorectal adenocarcinoma cells), LNCaP (Lymph Node Carcinoma of the Prostate), and HEK293 cell lines (Human embryonic kidney 293 cells) used to model colon, prostate, and non-cancerous cells. VT extract showed low DPPH and ABTS radical scavenging activities compared to standard antioxidants at 30 mg/ml concentration. In addition, it was determined that VT extract inhibited acetylcholinesterase enzyme.

Red meat consumption and risk for dyslipidaemia and inflammation: A systematic review and meta-analysis.

Aim: The study (PROSPERO: CRD42021240905) aims to reveal the relationships among red meat, serum lipids and inflammatory biomarkers. Methods and results: PubMed, EMBASE and the Cochrane databases were explored through December 2021 to identify 574 studies about red meat and serum lipids markers including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP) or hypersensitive-CRP (hs-CRP). Finally, 20 randomized controlled trials (RCTs) involving 1001 people were included, red meat and serum lipid markers and their relevant information was extracted. The pooled standard mean difference (SMD) was obtained by applying a random-effects model, and subgroup analyses and meta-regression were employed to explain the heterogeneity. Compared with white meat or grain diets, the gross results showed that the consumption of red meat increased serum lipid concentrations like TG (0.29 mmol/L, 95% CI 0.14, 0.44,P<0.001), but did not significantly influence the TC (0.13 mmol/L, 95% CI -0.07, 0.33, P = 0.21), LDL-C (0.11 mmol/L, 95% CI -0.23, 0.45, P = 0.53), HDL-C (-0.07 mmol/L, 95% CI -0.31, 0.17, P = 0.57),CRP or hs-CRP (0.13 mmol/L, 95% CI -0.10, 0.37,P = 0.273). Conclusion: Our study provided evidence to the fact that red meat consumption affected serum lipids levels like TG, but almost had no effect on TC, LDL-C, HDL-C and CRP or hs-CRP. Such diets with red meat should be taken seriously to avoid the problem of high lipid profiles. Systematic review registration: [https://www.crd.york.ac.uk/PROSPERO], identifier [CRD42021240905].

[Abundances and Morphology Patterns of Microplastics Under Different Land Use Types on the Loess Plateau].

As an emerging pollutant to the environment, microplastics have received widespread attention worldwide. The Loess Plateau, as one of the major agricultural production areas in China, has various land use types, but how the abundance and morphological patterns of microplastics differ among soils under different land use types remains unclear. In this study, we collected soils from three different land use types:croplands, apple orchards, and landfills in the Wangdonggou Catchment. Microplastics were separated and extracted using a modified density centrifugation method, and the abundance, composition, and morphological characteristics of the soil were analyzed and characterized using a laser infrared imaging system. The results showed that the average abundance of microplastics in the Wangdonggou Catchment was 4715 n·kg-1, mainly composed of PET, PU, and alkyd varnish(ALK), respectively accounting for 30.39%, 29.58%, and 8.42%. More than 80% of the microplastics were fragmented, and more than 60% of the microplastics were of a size ≤ 50 µm. The average abundance of microplastics varied significantly among land use types:cropland soil (7550 n·kg-1)>apple orchard soil (3440 n·kg-1)>landfill soil (2283 n·kg-1). The average area, width, height, eccentricity, circularity, and other morphological characteristics of microplastics in apple orchard soil were significantly different from those in the cropland and landfill soil.

[Visual analysis of exosomes in traditional Chinese medicine research and application status based on CiteSpace knowledge map].

In this study, CiteSpace was used to conduct bibliometric statistics and visualization of the research papers on the exosomes in traditional Chinese medicine(TCM) and application status in CNKI, Wanfang, VIP, and Web of Science. The authors, research institutions, and keywords of the relevant papers were analyzed to summarize the research status, hotspots, and development trends of TCM application of exosomes, thereby providing references for future research. A total of 340 Chinese papers and 9 English papers were included. In Chinese papers, GUO Hai-dong is the author with the largest amount of research papers, and his research interest is the mechanism of electroacupuncture in promoting functional recovery after sciatic nerve injury by regulating the release of exosomes. Shanghai University of Traditional Chinese Medicine is the research institution with the largest amount of papers, followed by Nanjing University of Chinese Medicine and Hunan University of Chinese Medicine. There was less cooperation among these research institutions, and cooperation between teams and agencies should be strengthened. The overall volume of publications in English was comparatively small, and the connections between the authors were weak. The publishing organizations were mostly distributed in medical schools, hospitals, comprehensive universities, and the cooperation between institutions was scattered. The main keywords in Chinese papers include microRNA, mesenchymal stem cells, bone marrow mesenchymal stem cells, mechanism of action, and extracellular vesicles. The research of exosomes in TCM is increasing in recent years. The research hotspot is that exosomes can both serve as biomarkers for the diagnosis and prognosis of certain diseases in TCM and drug carriers of Chinese medicine for targeted treatment of diseases. Keyword prominence suggested that exosomes derived from osteoblasts and macrophages in the treatment of diseases might still be a future research trend.

Synergistic Nanowire-Enhanced Electroporation and Electrochlorination for Highly Efficient Water Disinfection.

Conventional water disinfection methods such as chlorination typically involve the generation of harmful disinfection byproducts and intensive chemical consumption. Emerging electroporation disinfection techniques using nanowire-enhanced local electric fields inactivate microbes by damaging their outer structures without byproduct formation or chemical dosing. However, this physical-based method suffers from a limited inactivation efficiency under high water flux due to an insufficient contact time. Herein, we integrate electrochlorination with nanowire-enhanced electroporation to achieve a synergistic flow-through process for efficient water disinfection targeting bacteria and viruses. Electroporation at the cathode induces sub-lethal damages on the microbial outer structures. Subsequently, electrogenerated active chlorine at the anode aggravates these electroporation-induced injuries to the level of lethal damage. This sequential flow-through disinfection system achieves complete disinfection (>6.0-log) under a very high water flux of 2.4 × 104 L/(m2 h) with an applied voltage of 2.0 V. This disinfection efficiency is 8 times faster than that of electroporation alone. Further, the specific energy consumption for the disinfection by this novel process is extremely low (8 × 10-4 kW h/m3). Our results demonstrate a promising method for rapid and energy-efficient water disinfection by coupling electroporation with electrochlorination to meet vital needs for pathogen elimination.

Identification of a 3-Gene Prognostic Index for Papillary Thyroid Carcinoma.

The accurate determination of the risk of cancer recurrence is a critical unmet need in managing thyroid cancer (TC). Although numerous studies have successfully demonstrated the use of high throughput molecular diagnostics in TC prediction, it has not been successfully applied in routine clinical use, particularly in Chinese patients. In our study, we objective to screen for characteristic genes specific to PTC and establish an accurate model for diagnosis and prognostic evaluation of PTC. We screen the differentially expressed genes by Python 3.6 in The Cancer Genome Atlas (TCGA) database. We discovered a three-gene signature Gap junction protein beta 4 (GJB4), Ripply transcriptional repressor 3 (RIPPLY3), and Adrenoceptor alpha 1B (ADRA1B) that had a statistically significant difference. Then we used Gene Expression Omnibus (GEO) database to establish a diagnostic and prognostic model to verify the three-gene signature. For experimental validation, immunohistochemistry in tissue microarrays showed that thyroid samples' proteins expressed by this three-gene are differentially expressed. Our protocol discovered a robust three-gene signature that can distinguish prognosis, which will have daily clinical application.

A New Nomogram for Predicting the Risk of Intracranial Hemorrhage in Acute Ischemic Stroke Patients After Intravenous Thrombolysis.

Background: We aimed to develop and validate a new nomogram for predicting the risk of intracranial hemorrhage (ICH) in patients with acute ischemic stroke (AIS) after intravenous thrombolysis (IVT). Methods: A retrospective study enrolled 553 patients with AIS treated with IVT. The patients were randomly divided into two cohorts: the training set (70%, n = 387) and the testing set (30%, n = 166). The factors in the predictive nomogram were filtered using multivariable logistic regression analysis. The performance of the nomogram was assessed based on the area under the receiver operating characteristic curve (AUC-ROC), calibration plots, and decision curve analysis (DCA). Results: After multivariable logistic regression analysis, certain factors, such as smoking, National Institutes of Health of Stroke Scale (NIHSS) score, blood urea nitrogen-to-creatinine ratio (BUN/Cr), and neutrophil-to-lymphocyte ratio (NLR), were found to be independent predictors of ICH and were used to construct a nomogram. The AUC-ROC values of the nomogram were 0.887 (95% CI: 0.842-0.933) and 0.776 (95% CI: 0.681-0.872) in the training and testing sets, respectively. The AUC-ROC of the nomogram was higher than that of the Multicenter Stroke Survey (MSS), Glucose, Race, Age, Sex, Systolic blood Pressure, and Severity of stroke (GRASPS), and stroke prognostication using age and NIH Stroke Scale-100 positive index (SPAN-100) scores for predicting ICH in both the training and testing sets (p < 0.05). The calibration plot demonstrated good agreement in both the training and testing sets. DCA indicated that the nomogram was clinically useful. Conclusions: The new nomogram, which included smoking, NIHSS, BUN/Cr, and NLR as variables, had the potential for predicting the risk of ICH in patients with AIS after IVT.

Epidemiological and clinical characteristics of the chikungunya outbreak in Ruili City, Yunnan Province, China.

Chikungunya fever is an acute infectious disease caused by the chikungunya virus (CHIKV) that is characterized by fever, rash, and joint pain. CHIKV has infected millions of people in Africa, Asia, America, and Europe since it re-emerged in the Indian Ocean region in 2004. Here, we report an outbreak of Chikungunya fever that occurred in Ruili of Yunnan Province, a city located on the border between China and Myanmar, in September 2019. The outbreak lasted for three months from September to December. Overall, 112 cases were confirmed by a real-time reverse-transcription polymerase chain reaction in the Ruili People's Hospital, and they showed apparent temporal, spatial, and population aggregation. Among them, 91 were local cases distributed in 19 communities of Ruili City, and 21 were imported cases. The number of female patients was higher than that of male patients, and most patients were between 20 and 60 years old. The main clinical manifestations included joint pain (91.96%), fever (86.61%), fatigue (58.04%), chills (57.14%), rash (48.21%), headache (39.29%), and so forth. Biochemical indexes revealed increased C-reactive protein (63.39%), lymphopenia (57.17%), increased hemoglobin (33.04%), neutrophilia (28.57%), and thrombocytopenia (16.07%). Phylogenetic analysis of the complete sequences indicated that the CHIKV strains in this outbreak belonged to the Indian Ocean clade of the East/Central/South African genotype. We speculated that this chikungunya outbreak might be caused by CHIKV-infected persons returning from Myanmar, and provided a reference for the formulation of effective treatment and prevention measures.

Comparative research on separation and purification methods of neural stem cells / 中国药理学通报

Aim To explore and optimize the different separation and purification methods of neural stem cells (NSCs) , and compare the cell viability and purity after separation and purification.Methods (X) Separation of NSCs: The brains of ICR mice born within 24 h were isolated ( the cerebellum and olfactory bulb removed) , chopped and digested by mechanical pipetting, trypsin digestion, and PDD enzyme digestion.After sieving and centrifugation, the brain tissues were inoculated at a concentration of 1 X 10 • L , and cultured in serum-free medium to observe and compare the activity, proliferation and number of miscellaneous cells.(2) Purification of NSCs: The brain tissues of mice born within 24 h were isolated, and NSCs were purified by differential centrifugation and sieving, and the purity was identi-fied by immunofluorescence.Results NSCs separated by PDD enzyme digestion had high survival rate and rapid proliferation rate; the Nestin positive rate of NSCs in both Sieving assay and Differential centrifugation assay groups was higher than that of primary NSCs (59.14% ± 0.16% , P <0.05) , and the former (93.54% ± 0.02%) was higher than the latter (86.12% ± 0.04% ) .Conclusions The three separation methods can obtain a large amount of NSCs.Among them, the PDD enzymatic digestion method has little damage to the NSCs, and the neuro-sphere proliferation speed is fast; the NSCs obtained by the sieving assay have higher purity.

Recent progress and challenges in solution blow spinning.

In the past 30 years, researchers have worked towards reducing the size of ordinary three-dimensional (3D) materials into 1D or 2D materials in order to obtain new properties and applications of these low-dimensional systems. Among them, functional nanofibers with large surface area and high porosity have been widely studied and paid attention to. Because of the interesting properties of nanofibers, they find extensive application in filtration, wound dressings, composites, sensors, capacitors, nanogenerators, etc. Recently, a variety of nanofiber preparation methods such as melt blowing, electrospinning (e-spinning), centrifugal spinning and solution blow spinning (SBS) have been proposed. This paper includes a brief review of the fundamental principles of the preparation of nanofibers for solution jet spinning, the influence of experimental parameters, and the properties and potential applications of the solution-blown fibers. And the industrialization and challenges of SBS are also included.