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Abstract: Nondopaminergic neurotransmitters such as adenosine, norepinephrine, serotonin, glutamate, and acetylcholine are all involved in Parkinson's disease (PD) and promote its symptoms. Therefore, nondopaminergic receptors are key targets for developing novel preparations for the management of motor and non-motor symptoms in PD, without the potential adverse events of dopamine replacement therapy. We reviewed English-written articles and ongoing clinical trials of nondopaminergic treatments for PD patients till 2014 to summarize the recent findings on nondopaminergic preparations for the treatment of PD patients. The most promising research area of nondopaminergic targets is to reduce motor complications caused by traditional dopamine replacement therapy, including motor fluctuations and levodopa-induced dyskinesia. Istradefylline, Safinamide, and Zonisamide were licensed for the management of motor fluctuations in PD patients, while novel serotonergic and glutamatergic agents to improve motor fluctuations are still under research. Sustained- release agents of Amantadine were approved for treating levodopa induced dyskinesia (LID), and serotonin 5HT1B receptor agonist also showed clinical benefits to LID. Nondopaminergic targets were also being explored for the treatment of non-motor symptoms of PD. Pimavanserin was approved globally for the management of hallucinations and delusions related to PD psychosis. Istradefylline revealed beneficial effect on daytime sleepiness, apathy, depression, and lower urinary tract symptoms in PD subjects. Droxidopa may benefit orthostatic hypotension in PD patients. Safinamide and Zonisamide also showed clinical efficacy on certain non-motor symptoms of PD patients. Nondopaminergic drugs are not expected to replace dopaminergic strategies, but further development of these drugs may lead to new approaches with positive clinical implications.

Purpose Deficiency of adenosine deaminase 2 (DADA2), an autosomal recessive autoinflammatory disorder caused by biallelic loss-of-function variants in adenosine deaminase 2 (ADA2), has not been systemically investigated in Chinese population yet. We aim to further characterize DADA2 cases in China. Methods A retrospective analysis of patients with DADA2 identified through whole exome sequencing (WES) at seventeen rheumatology centers across China was conducted. Clinical characteristics, laboratory findings, genotype, and treatment response were analyzed. Results Thirty patients with DADA2 were enrolled between January 2015 and December 2021. Adenosine deaminase 2 enzymatic activity was low in all tested cases to confirm pathogenicity. Median age of disease presentation was 4.3 years and the median age at diagnosis was 7.8 years. All but one patient presented during childhood and two subjects died from complications of their disease. The patients most commonly presented with systemic inflammation (92.9%), vasculitis (86.7%), and hypogammaglobinemia (73.3%) while one patient presented with bone marrow failure (BMF) with variable cytopenia. Twenty-three (76.7%) patients were treated with TNF inhibitors (TNFi), while two (6.7%) underwent hematopoietic stem cell transplantation (HSCT). They all achieved clinical remission. A total of thirty-nine ADA2 causative variants were identified, six of which were novel. Conclusion To establish early diagnosis and improve clinical outcomes, genetic screening and/or testing of ADA2 enzymatic activity should be performed in patients with suspected clinical features. TNFi is considered as first line treatment for those with vascular phenotypes. HSCT may be beneficial for those with hematological disease or in those who are refractory to TNFi.

A rapid and simple method was developed for the synthesis of diarylmethyl thioethers via a DABCO-catalyzed 1,6-conjugate addition reaction of para-quinone methides (p-QMs) with organosulfur reagents.

Chiral pesticides account for 30% of pesticides. Pesticides are inevitably leached into the groundwater by runoff. At the watershed level, the distribution characteristics of enantiomers in sediments collected from the river network of an agricultural area near the middle and lower reaches of the Yangtze River were tested, and their potential correlations with the physicochemical properties and microbial communities of the sediments were analyzed. The sediment pollution was serious at sites 8 and 9, with their pollution source possibly being agricultural or industrial sewage. Moreover, there were higher cumulative contents of pesticide residues at sites 4, 8, and 9. Specifically, Cycloxaprid was the most detected chiral pesticide in the study area, followed by Dinotefuran and Diclofop-methyl. Additionally, Ethiprole and Difenoconazole had strong enantioselectivity in the study area. Interestingly, the enantiomers of some chiral pesticides, such as Tebuconazole, had completely different distributions at different sites. Pearson correlation analysis showed that sediment catalase and microbial biomass carbon were important factors for enantioselectivity of chiral pesticides. The effect of sediment physicochemical properties on enantioselective distribution was achieved by influencing the microorganisms in the sediment. Furthermore, the enantioselective distribution of Tebuconazole was closely related to the genus Arenimonas. Overall, the enantioselective distribution of most of the chiral pesticides was positively correlated with the prokaryotic microbial community. This study provides empirical support for agricultural non-point source pollution caused by chiral pesticides, and also lays a research foundation for exploring the factors that affect the fate of chiral pesticides in the environment.

In order to improve the cavitation performance of the self-excited oscillation nozzle (SEON), a novel SEON with a circular arc curve chamber was designed by changing the chamber wall profile of the SEON. The performance of the circular arc curve chamber SEON was studied numerically. Taking the vapor volume distribution and the vapor volume fraction as the evaluation indexes, the influences of the chamber wall profile on the cavitation performance of the circular arc curve chamber SEON were analyzed. In addition, it was compared with the broken-line chamber SEON. The numerical results show that the cavitation performance of the circular arc curve chamber SEON is first enhanced and then weakened by increasing the circular arc radius. The circular arc curve chamber structure can form a larger central cavitation volume in the nozzle, which improves the cavitation performance of the SEON. When the circular arc radius is 2 mm, the cavitation area and the turbulent kinetic energy of the circular arc curve chamber SEON increase by 122.5% and 16.9%.

While radiotherapy remains the cornerstone of head and neck cancer treatment, oral mucositis is a very serious side effect, especially grade III/IV oral mucositis. Oral mucositis not only seriously reduces the quality of life of patients, but also affects the ongoing treatment of patients. Use of honey for the remediation of oral mucositis promising, but clinically controversial. Therefore, to further ascertain its role in oral mucositis, an extensive literature search was performed in the Pubmed, Embase and Cochrane databases. Thirteen randomized controlled trials with 899 patients were included in the analysis. Pooled Odds ratio with 95% confidence intervals was analyzed. The results show that a significantly fewer number of patients treated with honey experienced grade III/IV oral mucositis after radiotherapy (OR 0.24, 95% CI 0.13–0.44, p < 0.001). The administration of honey concurrently with radiotherapy decreased the rate of graded III/IV oral mucositis. Thus, the use of honey during radiotherapy may represent a feasible strategy for preserving tolerance.

Menopause is accompanied with an increased risk of cardiovascular disease. DNA methylation may have a significant impact on postmenopausal women’s development of coronary heart disease. DNA methylation alterations in peripheral blood mononuclear cells (PBMCs) from women with coronary heart disease and healthy controls were detected using the Illumina Infinium MethylationEPIC BeadChip platform in this work. We employed Sangerbox technology and the GO and KEGG databases to further study the pathogenesis of coronary heart disease in postmenopausal women. After that, we used functional epigenetic module analysis and Cytoscape to remove the hub genes from the protein–protein interaction networks. Five genes (FOXA2, PTRD, CREB1, CTNAP2, and FBN2) were the hub genes. Lipid accumulation, endothelial cell failure, inflammatory responses, monocyte recruitment and aggregation, and other critical biological processes were all influenced by these genes. Finally, we employed methylation-specific PCR to demonstrate that FOXA2 was methylated at a high level in postmenopausal women with coronary heart disease. To better understand coronary heart disease in postmenopausal women’s molecular mechanisms, our study examine the major factors contributing to the state of DNA methylation modification, which will help discover novel diagnostic tools and treatment options.

The increasing trend of delaying childbirth means that more women are being diagnosed with breast cancer before having given birth to their desired number of children. Although chemotherapy can significantly improve the prognosis of this population, it also causes ovarian damage, including premature ovarian insufficiency and infertility. Gonadotropin-releasing hormone agonists (GnRHa) have shown promising fertility protective activity in premenopausal women, but their clinical usage remains controversial.Here, we conducted a meta-analysis to assess the efficacy of GnRHa when administered concurrently with chemotherapy that included cyclophosphamide in the prevention of chemotherapy-induced ovarian damage in premenopausal women.An extensive literature search was performed using the PubMed, Embase, and Cochrane databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were determined.Eleven randomized controlled trials with a total of 1,219 participants were included in the analyses. A significantly higher number of women treated with GnRHa experienced the resumption of ovarian function after chemotherapy than those who did not receive this treatment (OR, 3.04; 95% CI, 1.87-4.94; P0.001). Regarding spontaneous pregnancy, a statistically significant difference was observed only in hormone receptor-negative participants (OR, 2.06; 95% CI, 1.03-4.11; P = 0.04).When treating premenopausal women with breast cancer, the administration of GnRHa concurrently with chemotherapy appeared to improve the resumption rate of ovarian function; however, the spontaneous pregnancy rate only improved in hormone receptor-negative patients. Thus, the use of GnRHa during chemotherapy may represent a feasible strategy for preserving ovarian function in women with breast cancer.

Total sleep deprivation (TSD) leads to cognitive decline; however, the neurophysiological mechanisms underlying resting-state electroencephalogram (EEG) changes after TSD remain unclear. In this study, 42 healthy adult participants were subjected to 36 h of sleep deprivation (36 h TSD), and resting-state EEG data were recorded at baseline, after 24 h of sleep deprivation (24 h TSD), and after 36 h TSD. The analysis of resting-state EEG at baseline, after 24 h TSD, and after 36 h TSD using source localization analysis, power spectrum analysis, and functional connectivity analysis revealed a decrease in alpha-band power and a significant increase in delta-band power after TSD and impaired functional connectivity in the default mode network, precuneus, and inferior parietal lobule. The cortical activities of the precuneus, inferior parietal lobule, and superior parietal lobule were significantly reduced, but no difference was found between the 24 h and 36 h TSD groups. This may indicate that TSD caused some damage to the participants, but this damage temporarily slowed during the 24 h to 36 h TSD period.

Objectives: To investigate and compare the clinical outcomes of acute acromioclavicular joint (ACJ) dislocations treated by the Tight-Rope (TR) technique and clavicle hook plate (CHP). Methods: 34 patients with acute ACJ dislocation was treated by using TR technique in 16 patients (9 males, 5 females; mean age 38 years) and CHP in 20 patients (15 males, 5 females; mean age 33 years). Radiological and functional evaluations were routinely conducted with 1 year postoperatively. The mean follow up was 14.7 months. Results: All patients were statistically significant improvement in the constant score (CS), coracoclavicular (CC) distance, visual analogue scale (VAS) score at the last follow-up (P < 0.001). Compared with the CHP group, TR technique group had statistically significant shorter incision, length of stay, blood loss and subjective satisfactory score. (P < 0.001); The CS, CC distance and VAS score had no significant difference between two groups at the end of follow-up (P > 0.05). Patients who underwent CHP had a higher incidence of wound issue, osteolysis and osteoarthritisthan, while TR group had higher risk of re-dislocations. Conclusions: This study showed equivalent clinical efficacy of the TR and CHP techniques, with slightly different results including complications. We suggest that the choice of treatment for acute ACJ dislocation should be individually considered.

Due to the presence of physiological barriers, it is difficult to achieve the desired therapeutic efficacy of drugs; thus, it is necessary to develop an efficient drug delivery system that enables advanced functions such as self-monitoring. Curcumin (CUR) is a naturally functional polyphenol whose effectiveness is limited by poor solubility and low bioavailability, and its natural fluorescent properties are often overlooked. Therefore, we aimed to improve the antitumor activity and drug uptake monitoring by simultaneously delivering CUR and 5-Fluorouracil (5-FU) in the form of liposomes. In this study, dual drug-loaded liposomes (FC–DP–Lip) encapsulating CUR and 5-FU were prepared by the thin-film hydration method; their physicochemical properties were characterized; and their biosafety, drug uptake distribution in vivo, and tumor cell toxicity were evaluated. The results showed that the nanoliposome FC–DP–Lip showed good morphology, stability, and drug encapsulation efficiency. It showed good biocompatibility, with no side effects on zebrafish embryonic development. In vivo uptake in zebrafish showed that FC–DP–Lip has a long circulation time and presents gastrointestinal accumulation. In addition, FC–DP–Lip was cytotoxic against a variety of cancer cells. This work showed that FC–DP–Lip nanoliposomes can enhance the toxicity of 5-FU to cancer cells, demonstrating safety and efficiency, and enabling real-time self-monitoring functions.

The generation and exploitation of hot spots play a crucial role in the fabrication of highly sensitive surface-enhanced Raman scattering (SERS) substrates. In this work, silver nanosphere (AgNS) array substrates with various morphologies of polystyrene (PS) core/Ag shell were fabricated by reactive ion etching and glancing angle deposition technique on PS sphere templates. The electromagnetic field distribution (hot spots) of AgNS array was calculated by the finite difference time domain method. R6G and MB were used as probe molecules to investigate the effect of structure spacing on electric field enhancement. Under 785 nm excitation, an AgNS substrate with a gap of approximately 20 nm exhibited the best SERS enhancement, and the limit of detection reached 5×10-8 M for both analytes. These results serve as a reference for the development of a new highly sensitive SERS sensors.

Programmed cell death 1 receptor (PD-1) and its ligands constitute an inhibitory pathway to mediate the mechanism of immune tolerance and provide immune homeostasis. Significantly, the binding partners of PD-1 and its associated ligands are diverse, which facilitates immunosuppression in cooperation with other immune checkpoint proteins. Accumulating evidence has demonstrated the important immunosuppressive role of the PD-1 axis in the tumor microenvironment and in autoimmune diseases. In addition, PD-1 blockades have been approved to treat various cancers, including solid tumors and hematological malignancies. Here, we provide a comprehensive review of the PD-1 pathway, focusing on the structure and expression of PD-1, programmed cell death 1 ligand 1 (PD-L1), and programmed cell death 1 ligand 2 (PD-L2); the diverse biological functions of PD-1 signaling in health and immune-related diseases (including tumor immunity, autoimmunity, infectious immunity, transplantation immunity, allergy and immune privilege); and immune-related adverse events related to PD-1 and PD-L1 inhibitors.

Background: The negative consequences of drug addiction can include increased aggression, and previous research has suggested a correlation between drug addiction and self-harm. However, the relationship between childhood trauma, self-aggression, and drug addiction has not been extensively investigated. Methods: The present study to explore the influence of childhood trauma on self-aggression in drug users under the age of 16, used the benefits and barriers model. The study analyzed the distal factors of self-aggressive intention in compulsory drug addicts and examined the mediating role of sense of life meaning as a barrier factor and sensation seeking as a benefit factor. To collect data, the Childhood Trauma Questionnaire (CTQ), the Presence of Meaning in Life (MLQ-P), the Brief Sensation Seeking Scale (BSSS), and Aggression toward Self Scale (ATS) were administered to 625 male compulsory detoxification patients in a Sichuan compulsory detoxification facility. Results: The results showed no significant difference in self-aggression between methamphetamine and heroin addicts and identified a significant mediating effect of MLQ-P as a barrier factor and BSSS as a beneficial factor in predicting self-aggression. Conclusions: This study confirmed the applicability of the benefits and barriers model in the drug addicts, and proposed a parallel mediation model of CTQ affecting ATS with MLQ-P and BSSS as mediator variables. It can provide a theoretical basis for intervention in the recovery of drug addicts.

Objective To estimate the incidence of thromboembolism in children with primary nephrotic syndrome with Meta-analysis. Methods Relevant studies published from January 1, 1980 to December 31, 2021 were retrieved from Pubmed, Web of science, Cochrane library, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database(VIP) and Wangfang Database. Quality evaluation of the literatures included was conducted according to Agency for Healthcare Research and Quality(AHRQ) assessment tool, followed by data extraction and Meta-analysis with software RevMan 5.3. Results A total of seven studies involving 3675 subjects were included. The overall prevalence was 4.9% with 95% CI of 2.83 to 7.05.However, a significant heterogeneity (P I2 = 89%. The prevalence of venous thromboembolism was 3.3% with 95% CI of 1.7 to 4.9. The prevalence of arterial thromboembolism was 0.5% with 95% CI of 0.2 to 1.4. Conclusion Children with nephrotic syndrome are prone to thromboembolism, and it may lead to disability or death, therefore prevention measures is critical to decreasing the prevalence of thromboembolism.

Background Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for hematologic malignancies and non-malignant disorders, such as aplastic anemia, fanconi anemia, and certain immune deficiencies. Post-transplantation kidney injury is a common complication and involves a wide spectrum of structural abnormalities, including glomerular (MSPGN, mesangial proliferative glomerulonephritis; FSGS, focal segmental glomerulosclerosis; MPGN, membranoproliferative glomerulonephritis; MCD, minimal change disease), vascular (TMA, thrombotic microangiopathy), and/or tubulointerstitial (TIN, tubulointerstitial nephritis; ATI, acute tubular injury). Renal biopsy is the gold-standard examination for defining multiple etiologies of kidney impairment. Although kidney injury following HSCT has been studied, little is known about the effects of allo-HSCT on renal pathology in pediatric patients. Methods We retrospectively analyzed renal biopsy specimens from children with kidney injury after allo-HSCT and correlated results with clinical data in the last 10 years. Results Among 25 children (18 males and 7 females), three patients had proteinuria indicating nephrotic syndrome (24-hour urinary total protein/weight > 50 mg/kg/d), nine patients had severely reduced estimated glomerular filtration rate (eGFR 2) and four patients received kidney replacement therapy (KRT). The main pathologies identified from kidney biopsies were MSPGN (n = 12), FSGS (n = 12), MPGN (n = 5), TMA (n = 4), MCD (n = 3), diffuse glomerular fibrosis (DGF, n = 2), ATI and TIN, in isolation or combined with other pathologies. The median follow-up time was 16.5 (0.5 ~ 68.0) months. Three patients died of recurrent malignancy and/or severe infection, one child developed to end-stage renal disease (ESRD), six patients (24%) had elevated serum creatinine (SCr > 100µmol/l) and nine patients (36%) still had proteinuria. Conclusions This study evaluates histomorphologic findings from kidney biopsies of pediatric recipients following allo-HSCT. Detailed evaluation of renal biopsy samples is helpful to elucidate the nature of renal insult, and may potentially identify treatable disease processes.

This study explores the current status of pandemic fatigue, predictors, and their mechanisms of action based on a stress-response framework and a parallel model of future-oriented response. Study 1 investigated 8426 adult residents' understanding of and willingness to cooperate with the pandemic prevention and control policies, and found that public understanding of and willingness to cooperate with prevention policies were significantly lower in 2022 than in both 2020 and 2021. Study 2 surveyed 1635 residents on their motivation to prevent and control the pandemic. The results found that risk perception negatively predicted motivation to prevent and control the pandemic; perceived stress and preventive coping significantly mediated the relationship between risk perception and motivation to prevent and control the pandemic; but perceived stress and proactive coping did not significantly mediate the relationship between risk perception and motivation to prevent and control the pandemic. This revealed an increase in public fatigue in the third year of the pandemic. Pandemic fatigue can be predicted by pandemic risk perception, but the direct pathway of action is not significant and requires the mediation of perceived stress and preventive coping.

Chronic myeloid leukemia (CML) is a hematological tumor derived from hematopoietic stem cells. The aim of this study is to analyze the biological characteristics and identify the diagnostic markers of CML. We obtained the expression profiles from the Gene Expression Omnibus (GEO) database and identified 210 differentially expressed genes (DEGs) between CML and normal samples. These DEGs are mainly enriched in immune-related pathways such as Th1 and Th2 cell differentiation, primary immunodeficiency, T cell receptor signaling pathway, antigen processing and presentation pathways. Based on these DEGs, we identified two molecular subtypes using a consensus clustering algorithm. Cluster A was an immunosuppressive phenotype with reduced immune cell infiltration and significant activation of metabolism-related pathways such as reactive oxygen species, glycolysis and mTORC1; Cluster B was an immune activating phenotype with increased infiltration of CD4 + and CD8 + T cells and NK cells, and increased activation of signaling pathways such as interferon gamma (IFN-γ) response, IL6-JAK-STAT3 and inflammatory response. Drug prediction results showed that patients in Cluster B had a higher therapeutic response to anti-PD-1 and anti-CTLA4 and were more sensitive to imatinib, nilotinib and dasatinib. Support Vector Machine Recursive Feature Elimination (SVM-RFE), Least Absolute Shrinkage Selection Operator (LASSO) and Random Forest (RF) algorithms identified 4 CML diagnostic genes (HDC, SMPDL3A, IRF4 and AQP3), and the risk score model constructed by these genes improved the diagnostic accuracy. We further validated the diagnostic value of the 4 genes and the risk score model in a clinical cohort, and the risk score can be used in the differential diagnosis of CML and other hematological malignancies. The risk score can also be used to identify molecular subtypes and predict response to imatinib treatment. These results reveal the characteristics of immunosuppression and metabolic reprogramming in CML patients, and the identification of molecular subtypes and biomarkers provides new ideas and insights for the clinical diagnosis and treatment.

Differentially Methylated CpG Sites (2173 Sites) in 24 Nasopharyngeal Carcinoma (NPC) Tissues and 24 Non-cancer Nasopharyngitis Biopsy Tissues (NCNBT)

Kaplan-Meier curves estimation of disease-free survival (DFS) and overall survival (OS) for patients with high or low methylation levels stratified by tumor stage or the receipt of concurrent chemotherapy.

Supplementary Table S1: Clinicopathological Characteristics of 24 NPC and 24 NCNBT Supplementary Table S2: Clinical Characteristics of Nasopharyngeal Carcinoma Patients According to Gene Methylation Panel in Training, Validation, and Independent Cohorts. Supplementary Table S3: Primer Sequences of 28 Genes and GAPDH Supplementary Table S4: Primer Used for Pyrosequencing Methylation Analysis of Candidate Genes Supplementary Table S6: Data Analysis with PubMeth and NCBI PubMed Supplementary Table S7: Correlation Analysis between Methylation of Six Genes in the Training Cohort

Representative Pyrograms of Methylation Analysis by Bisulfite Pyrosequencing.

A fresh heterocycle compound, namely, 1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4, 5, 6, 7-tetrahydro-1H-pyrazolo[3, 4-c]pyridine-3-carboxylic acid (1), was synthesized by employing 1-(4-aminophenyl)-3-morpholino-5, 6-dihydropyridin-2(1H)-one as the raw material through multiple generation routes. The new compound was characterized by infrared spectroscopy, 1H nuclear magnetic resonance, and single-crystal Xray diffraction. The nursing and treatment applications of the compound against children bronchial pneumonia were examined, and the detailed mechanism was simultaneously analyzed. The release of TNF-α and IL-1β into the alveolar lavage fluid was detected with enzyme-linked immunosorbent assay. Additionally, real-time polymerase chain reaction (RT-PCR) was exploited for identifying the NF-κB activation levels in the epithelial cells of respiratory tract mucosa. Results from the atomistic scale by molecular docking simulation suggest that compound 1 has excellent biological activity, and three hydrogen bonds are formed between compound 1 and the receptor.

Cepharanthine (CEP) is an active alkaloid isolated from Stephania Cepharantha Hayata. It is reported that the anti-inflammatory properties of CEP could be employed to treat a variety of diseases. In this study, we first found that CEP ameliorates ulcerative colitis (UC) induced by DSS. The effect of CEP on gut microbiota was further evaluated by 16S rRNA gene sequencing, antibiotic pretreatment and faecal microbiota transplantation (FMT). Results showed that the abundances of gut microbiota, such as Romboutsia, Turicibacter and Escherichia-Shigella (especially Romboutsia), were significantly reduced after CEP treatment. Additionally, we explored the mechanisms of CEP by a strategy integrating transcriptomics with network pharmacology. The transcriptome data confirmed that CEP functioned through cytokine and cytokine receptor pathways. The expression levels of 10 pro-inflammatory hub genes (such as CXCL1, CXCL9, CCL7) were positively correlated with the abundance of Romboutsia. Our data identified Romboutsia as a potential pathobiont in UC. Collectively, we confirmed that CEP relieved colon inflammation by modulating gut microbiota and pro-inflammatory cytokine expression. CEP can be adopted to design novel effective therapeutic strategies for UC.

SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.

Traditionally, the strata of the Luonie Valley, Dechang County, SW Sichuan, China, are considered to contain a suite of felsic volcanic rocks (the Huili Group) that erupted after c. 1050 Ma. However, we report here new age constraints, elemental and Lu–Hf isotope geochemistry for a different suite of older basaltic agglomerate lava, basaltic tuff lava and basalt from the same area, which we name the Luonie Formation. New dating results show that the basaltic volcanic suite of the upper part of the Luonie Formation formed at 1126.1 ± 9.9 Ma, significantly earlier than deposition of the Huili Group, but comparable in age to the 1142 ± 16 Ma Laowushan Formation in central Yunnan Province. Granite intrusion into the Luonie Formation dated 1050.7 ± 12.7 Ma provides crucial supporting evidence for this earlier depositional age. We also report a maximum sedimentary age of c. 1158 Ma for the underlying arkose, implying stratigraphic conformity with the basaltic volcanic rock suite.The ϵHf(t) values of the basaltic volcanic rocks are mainly positive, indicating that the rocks are mainly derived from the depleted mantle and slightly stained by crustal materials. The characteristics of P*, Nb* and Zr* anomalies also support this view. The distribution patterns of trace and rare earth elements indicate that the basaltic volcanic rocks formed in an extensional setting. The Zr/4–Y–2Nb and Th–Nb/16–Zr/117 discrimination diagrams also provide evidence for this understanding. Lithofacies analysis shows that basaltic volcanic wrocks with the characteristics of both continental and marine facies should be formed in a littoral–neritic environment. We propose here that the evidence is consistent with a phase of continental extension that preceded the convergence of the SW Yangtze Block to form part of Rodinia.

In this work, based on the unique scaffold of indirubin, we synthesized 29 indirubin-3′-monoximes and preliminarily evaluated their antibacterial activities, especially against S. aureus.

This article deals with a new modified heat conduction model with fractional order that includes the Caputo–Fabrizio differential operator (CF) and the thermal relaxation time. This new approach to the CF fractional derivative has attracted many researchers because it includes a nonsingular kernel. The nonlocal theory proposed by Eringen has also been applied to demonstrate the effect of scale-dependent thermoelastic materials. The problem of thermal isotropic semi-infinite space is addressed as an application of the presented model. The medium is exposed to regularly changing heat sources and is initially placed in a continuous external magnetic field. The system of governing equations was expressed in the field of the Laplace transform, and the problem in this field was solved by the state-space operation. The inverse of the transformed expressions of physical quantities is found numerically using Zakian’s algorithm. The effects of the nonlocal parameter, the fractal order parameter, and the magnetic field were graphically presented and analyzed in detail. Some of the previous investigations were extracted in some special cases.

Biomimetic materials have emerged as attractive and competitive alternatives for tissue engineering (TE) and regenerative medicine. In contrast to conventional biomaterials or synthetic materials, biomimetic scaffolds based on natural biomaterial can offer cells a broad spectrum of biochemical and biophysical cues that mimic the in vivo extracellular matrix (ECM). Additionally, such materials have mechanical adaptability, microstructure interconnectivity, and inherent bioactivity, making them ideal for the design of living implants for specific applications in TE and regenerative medicine. This paper provides an overview for recent progress of biomimetic natural biomaterials (BNBMs), including advances in their preparation, functionality, potential applications and future challenges. We highlight recent advances in the fabrication of BNBMs and outline general strategies for functionalizing and tailoring the BNBMs with various biological and physicochemical characteristics of native ECM. Moreover, we offer an overview of recent key advances in the functionalization and applications of versatile BNBMs for TE applications. Finally, we conclude by offering our perspective on open challenges and future developments in this rapidly-evolving field.

Background: Previous studies revealed that sleep deprivation (SD) impairs risk perception and leads to poor decision-making efficiency. However, how risk perception is related to brain regions’ communication after SD has not been elucidated. In this study, we investigated the neuropsychological mechanisms of SD-impaired risk perception. Methods: Nineteen healthy male adults were recruited and underwent resting-state functional magnetic resonance imaging during a state of rested wakefulness and after nearly 36 h of total SD. They then completed the balloon analog risk task, which was used to measure the risk perception ability of risky decision-making. Regional homogeneity (ReHo) and voxel-wise functional connectivity were used to investigate neurobiological changes caused by SD. Correlation analysis was used to investigate the relationship between changes in ReHo, function, and risk perception. Results: At the behavioral level, risk perception decreased after 36 h of SD. At the neural level, SD induced a significant increase in ReHo in the right postcentral gyrus and was positively correlated with risk perception changes. The functional connectivity between the right postcentral gyrus, left medial temporal gyrus, and right inferior temporal gyrus was enhanced. Critically, increased right postcentral gyrus and right inferior temporal gyrus connectivity positively correlated with changes in risk perception. Conclusions: SD impairs the risk perception associated with altered postcentral connectivity. The brain requires more energy to process and integrate sensory and perceptual information after SD, which may be one possible reason for decreased risk perception ability after SD.

ObjectiveTo establish a logistic regression model based on CT and MRI imaging features and Epstein-Barr (EB) virus nucleic acid to develop a diagnostic score model to differentiate extranodal NK/T nasal type (ENKTCL) from diffuse large B cell lymphoma (DLBCL).MethodsThis study population was obtained from two independent hospitals. A total of 89 patients with ENKTCL (n = 36) or DLBCL (n = 53) from January 2013 to May 2021 were analyzed retrospectively as the training cohort, and 61 patients (ENKTCL=27; DLBCL=34) from Jun 2021 to Dec 2022 were enrolled as the validation cohort. All patients underwent CT/MR enhanced examination and EB virus nucleic acid test within 2 weeks before surgery. Clinical features, imaging features and EB virus nucleic acid results were analyzed. Univariate analyses and multivariate logistic regression analyses were performed to identify independent predictors of ENKTCL and establish a predictive model. Independent predictors were weighted with scores based on regression coefficients. A receiver operating characteristic (ROC) curve was created to determine the diagnostic ability of the predictive model and score model.ResultsWe searched for significant clinical characteristics, imaging characteristics and EB virus nucleic acid and constructed the scoring system via multivariate logistic regression and converted regression coefficients to weighted scores. The independent predictors for ENKTCL diagnosis in multivariate logistic regression analysis, including site of disease (nose), edge of lesion (blurred), T2WI (high signal), gyrus like changes, EB virus nucleic acid (positive), and the weighted score of regression coefficient was 2, 3, 4, 3, 4 points. The ROC curves, AUCs and calibration tests were carried out to evaluate the scoring models in both the training cohort and the validation cohort. The AUC of the scoring model in the training cohort were 0.925 (95% CI, 0.906-0.990) and the cutoff point was 5 points. In the validation cohort, the AUC was 0.959 (95% CI, 0.915-1.000) and the cutoff value was 6 points. Four score ranges were as follows: 0-6 points for very low probability of ENKTCL, 7-9 points for low probability; 10-11 points for middle probability; 12-16 points for very high probability.ConclusionThe diagnostic score model of ENKTCL based on Logistic regression model which combined with imaging features and EB virus nucleic acid. The scoring system was convenient, practical and could significantly improve the diagnostic accuracy of ENKTCL and the differential diagnosis of ENKTCL from DLBCL.