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Mei Ye,1,2 Xin Chen,1,3 Yu Wang,4 Yan-Heng Zhou,5 Wei Pang,1 Chiyu Zhang,6 Yong-Tang Zheng1,4 1Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, People’s Republic of China; 2Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101408, People’s Republic of China; 3Department of Pathogenic Biology, School of Basic Medical Sciences, Gannan Medical University, Ganzhou 341000, People’s Republic of China; 4KIZ-SU Joint Laboratory of Animal Model and Drug Development, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215000, People’s Republic of China; 5Shaanxi Engineering and Technological Research Center for Conversation and Utilization of Regional Biological Resources, College of Life Sciences, Yan’an University, Yan’an, Shaanxi 716000, People’s Republic of China; 6Pathogen Discovery and Evolution Unit, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200025, People’s Republic of ChinaCorrespondence: Yong-Tang ZhengKey Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, 32 Jiaochang Donglu, Kunming, People’s Republic of ChinaTel/Fax +86 871 65195684Email zhengyt@mail.kiz.ac.cnChiyu ZhangPathogen Discovery and Evolution Unit, Institute Pasteur of Shanghai, 320 Yueyang Road, Shanghai, People’s Republic of ChinaTel/Fax +86 21 54923051Email zhangcy1999@ips.ac.cnBackground: Estimating the prevalence and characterizing the transmission of HIV-1 drug resistance in treatment-naïve individuals are very important in the prevention and control of HIV/AIDS. As one of the areas most affected by HIV/AIDS, few data are currently available for HIV-1 drug resistance in antiretroviral therapy (ART)-naïve individuals in Myanmar, which borders Yunnan, China.Methods: HIV-1 pol sequences from ART-naïve HIV-1-infected individuals during 2008 and 2014 in Myanmar were retrieved from our previous studies. HIV-1 transmitted drug resistance (TDR) and susceptibility to antiretroviral drugs were predicted using the Stanford HIVdb program. HIV-1 transmission cluster (TC) was determined by Cluster Picker.Results: A total of 169 partial pol sequences from ART-naïve HIV-1 positive Burmese were analyzed. The prevalence of TDR was 20.1%. CRF01_AE and BC recombinants appeared to have a higher prevalence of TDR than other subtypes. The V179D/T was found to be very common in the China–Myanmar border region and was involved in half of the transmission clusters formed by HIV-1 drug-resistance strains in this region. Comparison showed that drug-resistance mutation profile in Myanmar was very similar to that in Dehong prefecture of Yunnan. By further phylogenetic analysis with all available sequences from the China–Myanmar border region, four HIV-1 drug-resistance-related TCs were identified. Three of them were formed by Burmese long-distance truck drivers and the Burmese staying in Yunnan, and another was formed by Burmese injection drug users staying in Myanmar and Yunnan. These results suggest a potential transmission link of HIV-1 drug resistance between Myanmar and Yunnan.Conclusion: Given the high prevalence of TDR in Myanmar, and the potential risk of cross-border transmission of HIV-1 drug-resistant strains between Myanmar and Yunnan, China, ongoing monitoring of HIV-1 drug resistance in ART-naïve individuals will provide a guideline for clinical antiretroviral treatment and benefit the prevention and control of HIV/AIDS in this border region.Keywords: HIV-1, antiretroviral therapy, transmission cluster, drug-resistance mutations, ART-naïve, Myanmar, Yunnan

Human immunodeficiency virus-1 (HIV-1) infection disrupts the homeostatic equilibrium between the host and commensal microbes. However, the dynamic changes of plasma commensal viruses and their role in HIV/simian immunodeficiency virus (SIV) pathogenesis are rarely reported. Here, we investigated the longitudinal changes of plasma virome, inflammation levels, and disease markers using an SIV-infected Macaca leonina model. Large expansions of plasma Anelloviridae , Parvoviridae , Circoviridae and other commensal viruses, and elevated levels of inflammation and D-dimer were observed since the chronic phase of SIV infection. Anelloviridae abundance appears to correlate positively with the CD4 + T cell count but negatively with SIV load especially at the acute phase, whereas other commensal viruses' abundances show opposite correlations with the two disease markers. Antiretroviral therapy slightly reduces but does not substantially reverse the expansion of commensal viruses. Furthermore, 1387 primate anellovirus open reading frame 1 sequences of more than 1500 nucleotides were annotated. The data reveal different roles of commensal viruses in SIV pathogenesis.

Abstract: The hypothalamic paraventricular nucleus (PVN) plays a central role in regulating cardiovascular activity and blood pressure. We administered hydroxylamine hydrochloride (HA), a cystathionine-β-synthase inhibitor, into the PVN to suppress endogenous hydrogen sulfide and investigate its effects on the mitogen-activated protein kinase (MAPK) pathway in high salt (HS)-induced hypertension. We randomly divided 40 male Dahl salt-sensitive rats into 4 groups: the normal salt (NS) + PVN vehicle group, the NS + PVN HA group, the HS + PVN vehicle group, and the HS + PVN HA group, with 10 rats in each group. The rats in the NS groups were fed a NS diet containing 0.3% NaCl, while the HS groups were fed a HS diet containing 8% NaCl. The mean arterial pressure was calculated after noninvasive measurement using an automatic sphygmomanometer to occlude the tail cuff once a week. HA or vehicle was infused into the bilateral PVN using Alzet osmotic mini pumps for 6 weeks after the hypertension model was successfully established. We measured the levels of H 2 S in the PVN and plasma norepinephrine using enzyme linked immunosorbent assay. In addition, we assessed the parameters of the MAPK pathway, inflammation, and oxidative stress through western blotting, immunohistochemical analysis, or real-time polymerase chain reaction. In this study, we discovered that decreased levels of endogenous hydrogen sulfide in the PVN contributed to the onset of HS-induced hypertension. This was linked to the activation of the MAPK signaling pathway, proinflammatory cytokines, and oxidative stress in the PVN, as well as the activation of the sympathetic nervous system., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

HIV/AIDS cannot be cured because of the persistence of the viral reservoir. Because of the complexity of the cellular composition and structure of the human organs, HIV reservoirs of anatomical site are also complex. Recently, although a variety of molecules have been reported to be involved in the establishment and maintenance of the viral reservoirs, or as marker of latent cells, the research mainly focuses on blood and lymph nodes. Now, the characteristics of the viral reservoir in tissue are not yet fully understood. In this study, various tissues were collected from SIVmac239-infected monkeys, and the level of total SIV DNA, SIV 2-LTR DNA, and cell-associated virus RNA in them were compared with character of the anatomical viral reservoir under early treatment. The results showed that short-term combination antiretroviral therapy (cART) starting from 3 days after infection could significantly inhibit viremia and reduce the size of the anatomical viral reservoir, but it could not eradicate de novo infections and ongoing replication of virus. Moreover, the effects of early cART on the level of total SIV DNA, SIV 2-LTR DNA, and cell-associated virus RNA in different tissues were different, which changed the size distribution of viral reservoir in anatomical site. Finally, the contribution of nonlymphoid tissues, especially liver and lung, to the viral reservoir increased after treatment, while the contribution of intestinal lymphoid to the viral reservoir significantly reduced. These results suggested that early treatment effectively decreased the size of viral reservoir, and that the effects of cART on the tissue viral reservoir varied greatly by tissue type. The results implied that persistent existence of virus in nonlymphoid tissues after short-term treatment suggested that the role of nonlymphoid tissues cannot be ignored in development strategies for AIDS therapy.

Nanoparticles composed of Levan and Dolutegravir (DTG) have been successfully synthesized using a spray drying procedure specifically designed for milk/food admixture applications. Levan, obtained from the microorganism Bacillus subtilis, was thoroughly characterized using MALDI-TOF and solid-state NMR technique to confirm its properties. In the present study, this isolated Levan was utilized as a carrier for drug delivery applications. The optimized spray-dried nanoparticles exhibited a smooth surface morphology with particle sizes ranging from 195 to 329 nm. In the in-vitro drug release experiments conducted in water media, the spray-dried nanoparticles showed 100 % release, whereas the unprocessed drug exhibited only 50 % release at the end of 24 h. Notably, the drug release in milk was comparable to that in plain media, indicating the compatibility. The improved dissolution rate observed for the nanoparticles could be attributed to the solid-state conversion (confirmed by XRD analysis) of DTG from its crystalline to amorphous state. The stability of the drug was verified using Fourier Transform Infra-Red Spectroscopy and Thermogravimetry-Differential Scanning Calorimetry analysis. To evaluate the in-vitro cellular toxicity, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was conducted, which revealed the CC 50 value of 88.88 ± 5.10 µg/mL for unprocessed DTG and 101.08 ± 37.37 µg/mL for DTG nanoparticles. These results indicated that the toxicity of the nanoparticles was comparable to the unprocessed drug. Furthermore, the anti-HIV activity of the nanoparticles in human cell lines was found to be similar to that of the pure drug, emphasizing the therapeutic efficacy of DTG in combating HIV., Competing Interests: Declaration of competing interest None., (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

The tree shrew ( Tupaia belangeri ) has long been proposed as a suitable alternative to non-human primates (NHPs) in biomedical and laboratory research due to its close evolutionary relationship with primates. In recent years, significant advances have facilitated tree shrew studies, including the determination of the tree shrew genome, genetic manipulation using spermatogonial stem cells, viral vector-mediated gene delivery, and mapping of the tree shrew brain atlas. However, the limited availability of tree shrews globally remains a substantial challenge in the field. Additionally, determining the key questions best answered using tree shrews constitutes another difficulty. Tree shrew models have historically been used to study hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, myopia, and psychosocial stress-induced depression, with more recent studies focusing on developing animal models for infectious and neurodegenerative diseases. Despite these efforts, the impact of tree shrew models has not yet matched that of rodent or NHP models in biomedical research. This review summarizes the prominent advancements in tree shrew research and reflects on the key biological questions addressed using this model. We emphasize that intensive dedication and robust international collaboration are essential for achieving breakthroughs in tree shrew studies. The use of tree shrews as a unique resource is expected to gain considerable attention with the application of advanced techniques and the development of viable animal models, meeting the increasing demands of life science and biomedical research.

The distribution of the immune system throughout the body complicates in vitro assessments of coronavirus disease 2019 (COVID-19) immunobiology, often resulting in a lack of reproducibility when extrapolated to the whole organism. Consequently, developing animal models is imperative for a comprehensive understanding of the pathology and immunology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This review summarizes current progress related to COVID-19 animal models, including non-human primates (NHPs), mice, and hamsters, with a focus on their roles in exploring the mechanisms of immunopathology, immune protection, and long-term effects of SARS-CoV-2 infection, as well as their application in immunoprevention and immunotherapy of SARS-CoV-2 infection. Differences among these animal models and their specific applications are also highlighted, as no single model can fully encapsulate all aspects of COVID-19. To effectively address the challenges posed by COVID-19, it is essential to select appropriate animal models that can accurately replicate both fatal and non-fatal infections with varying courses and severities. Optimizing animal model libraries and associated research tools is key to resolving the global COVID-19 pandemic, serving as a robust resource for future emerging infectious diseases.

Objective: To explore clnical efficacy of modified Frosch approach for Schatzker typeⅡtibial plateau fracture with posterolateral column., Methods: From January 2019 to September 2020, totally 11 patients with Schatzker typeⅡtibial plateau fractures with posterolateral column were treated, including 7 males and 4 females, aged from 21 to 49 years old. Modified Frosch approach was adopted for lateral decubitus position, and posterolateral fractures were fixed with support plates or posterolateral screws. Anterolateral fixation with conventional tibial plateau lateral locking plate. Tibial plateau varus angle and posterior inclination angle were measured by X-ray immediately and 12 months after operation, as well as knee motion at 12 months after operation. Knee function at 12 months after operation was evaluated by knee score of Hospital for Special Surgery(HSS)., Results: Eleven patients were followed up for 12 to 15 months. Varus angle and inclination angle at immediately after operation ranged from 76° to 86° and 6° to 10°, respectively, and 79° to 88° and 6° to 10°, respectively at 12 months after operation. The range of extension of knee ranged from 0° to 5°, and flexion was 106° to 137° at 12 months after operation. Postoperative HSS knee score at 12 months ranged from 74 to 94 scores, 8 patients were excellent and 3 good., Conclusion: Modified Frosch approach is an effective surgical method for Schatzker typeⅡtibial plateau fracture with posterolateral column. A single incision is used to complete fracture exposure and fixation at two sites, avoiding use of combined incisions, and could obtain good postoperative knee joint function. During operation, popliteal fossa structure should be familiar, and the common peroneal nerve should be protected to avoid injury.

Selective recognition and enrichment of fullerenes ( e.g. , C 60 and C 70 ) remains challenging due to the same diameter and geometrical similarity. Herein, we report a hexagonal anthracene-based nanotube (1) through a one-pot Suzuki-Miyaura cross-coupling reaction. With anthracene-based side walls and pyridine linkers, 1 features a nano-scale tubular cavity measuring 1.2 nm in diameter and 0.9 nm in depth, along with pH-responsive properties. Interestingly, the electron-rich 1 shows high binding affinity ( K a ≈ 10 6 M -1 ) and selectivity ( K s ≈ 140) to C 70 over C 60 in toluene, resulting from their different contribution of π-π interactions with the host. The protonation of 1 simultaneously alters the electronic properties within the nanotube, resulting in the release of the fullerene guests. Lastly, the selective recognition and pH stimuli-responsive properties of the nanotube have been utilized to enrich C 70 from its low-content mixtures of fullerenes in chloroform., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Considering that CO 2 reduction is mostly a multielectron reaction, it is necessary for the photocatalysts to integrate multiple catalytic sites and cooperate synergistically to achieve efficient photocatalytic CO 2 reduction to various products, such as C 2 hydrocarbons. Herein, through crystal engineering, we designed and constructed a metal-organic framework-derived Zr/Ti bimetallic oxide solid solution support, which was confirmed by X-ray diffraction, electron microscopy and X-ray absorption spectroscopy. After anchoring Au nanoparticles, the composite photocatalyst exhibited excellent performances toward photocatalytic CO 2 reduction to syngas (H 2 and CO production rates of 271.6 and 260.6 μmol g -1  h -1 ) and even C 2 hydrocarbons (C 2 H 4 and C 2 H 6 production rates of 6.80 and 4.05 μmol g -1  h -1 ). According to the control experiments and theoretical calculations, the strong interaction between bimetallic oxide solid solution support and Au nanoparticles was found to be beneficial for binding intermediates and reducing CO 2 reduction, highlighting the synergy effect of the catalytic system with multiple active sites., (© 2024 Wiley-VCH GmbH.)

A new lignan phyllanins A ( 1 ) and a lignan phyllanins B ( 2 ) for which the absolute configuration was determined for the first time, along with four known lignans ( 3 - 6 ) were isolated from the branch and leaf extracts of Phyllanthodendron dunnianum . Their planar structures were mainly determined by a combination of 1D and 2D NMR, HRESIMS spectral analyses, and the absolute configurations of the compounds 1 and 2 were established by DFT GIAO 13 C NMR and electronic circular dichroism (ECD) calculations. In addition, all these six lignans were firstly tested for the antibacterial activities against MRSA, Staphylococcus aureus , Enterococcus faecalis , Pseudomonas aeruginosa and Escherichia coli . Among these compounds, 2 and 5 showed potential antibacterial activities against MRSA and S. aureus with MIC values of 4 and 8 µg/mL, respectively.

Objectives: There is conflicting data regarding the response of older people with HIV (PWH) to antiretroviral therapy (ART). The objective of this study was to evaluate the long-term immunological and virological responses, changes in regimen, and adverse drug reactions (ADRs) in older participants (50+ years) compared with younger (18-34 years) and middle-aged (35-49 years) PWH., Methods: A retrospective review of medical records was conducted on 1622 participants who received ART in Yunnan Province, China, from 2010 to 2019. The study compared CD4+ T-cell counts, CD4+/CD8+ ratio, and relative numbers between different groups using the Kruskal-Wallis test. Cox proportional hazards regression models were used to identify variables associated with the occurrence of immune reconstitution insufficiency. The rates of immune reconstitution, incidence of ADRs, and rates of treatment change were analyzed using the chi-squared test or Fisher's exact test., Results: Over 95% achieved viral load 200 copies/ml or less, with no age-related difference. However, older participants exhibited significantly lower CD4+ T-cell counts and CD4+/CD8+ recovery post-ART (P < 0.001), with only 32.21% achieving immune reconstitution (compared with young: 52.16%, middle-aged: 39.29%, P < 0.001) at the end of follow-up. Middle-aged and elderly participants changed ART regimens more because of ADRs, especially bone marrow suppression and renal dysfunction., Conclusion: Although the virological response was consistent across age groups, older individuals showed poorer immune responses and higher susceptibility to side effects. This underscores the need for tailored interventions and comprehensive management for older patients with HIV., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Apart from mediating viral entry, the function of the free HIV-1 envelope protein (gp120) has yet to be elucidated. Our group previously showed that EP2 derived from one β-strand in gp120 can form amyloid fibrils that increase HIV-1 infectivity. Importantly, gp120 contains ~30 β-strands. We examined whether gp120 might serve as a precursor protein for the proteolytic release of amyloidogenic fragments that form amyloid fibrils, thereby promoting viral infection. Peptide array scanning, enzyme degradation assays, and viral infection experiments in vitro confirmed that many β-stranded peptides derived from gp120 can indeed form amyloid fibrils that increase HIV-1 infectivity. These gp120-derived amyloidogenic peptides, or GAPs, which were confirmed to form amyloid fibrils, were termed gp120-derived enhancers of viral infection (GEVIs). GEVIs specifically capture HIV-1 virions and promote their attachment to target cells, thereby increasing HIV-1 infectivity. Different GAPs can cross-interact to form heterogeneous fibrils that retain the ability to increase HIV-1 infectivity. GEVIs even suppressed the antiviral activity of a panel of antiretroviral agents. Notably, endogenous GAPs and GEVIs were found in the lymphatic fluid, lymph nodes, and cerebrospinal fluid (CSF) of AIDS patients in vivo. Overall, gp120-derived amyloid fibrils might play a crucial role in the process of HIV-1 infectivity and thus represent novel targets for anti-HIV therapeutics., (© 2024. The Author(s), under exclusive licence to CSI and USTC.)

SARS-CoV-2 infection-induced hyper-inflammation is a key pathogenic factor of COVID-19. Our research, along with others', has demonstrated that mast cells (MCs) play a vital role in the initiation of hyper-inflammation caused by SARS-CoV-2. In previous study, we observed that SARS-CoV-2 infection induced the accumulation of MCs in the peri-bronchus and bronchioalveolar-duct junction in humanized mice. Additionally, we found that MC degranulation triggered by the spike protein resulted in inflammation in alveolar epithelial cells and capillary endothelial cells, leading to subsequent lung injury. The trachea and bronchus are the routes for SARS-CoV-2 transmission after virus inhalation, and inflammation in these regions could promote viral spread. MCs are widely distributed throughout the respiratory tract. Thus, in this study, we investigated the role of MCs and their degranulation in the development of inflammation in tracheal-bronchial epithelium. Histological analyses showed the accumulation and degranulation of MCs in the peri-trachea of humanized mice infected with SARS-CoV-2. MC degranulation caused lesions in trachea, and the formation of papillary hyperplasia was observed. Through transcriptome analysis in bronchial epithelial cells, we found that MC degranulation significantly altered multiple cellular signaling, particularly, leading to upregulated immune responses and inflammation. The administration of ebastine or loratadine effectively suppressed the induction of inflammatory factors in bronchial epithelial cells and alleviated tracheal injury in mice. Taken together, our findings confirm the essential role of MC degranulation in SARS-CoV-2-induced hyper-inflammation and the subsequent tissue lesions. Furthermore, our results support the use of ebastine or loratadine to inhibit SARS-CoV-2-triggered degranulation, thereby preventing tissue damage caused by hyper-inflammation., Competing Interests: Conflict of interest The authors declare no conflict of interest. Prof. Ling Chen and Prof. Jian-Hua Wang are editorial board members for Virologica Sinica and were not involved in the editorial review or the decision to publish this article., (Copyright © 2024 The Authors. Publishing services by Elsevier B.V. All rights reserved.)

Chemical investigation of an EtOAc extract of the endophytic fungus Pseudocercospora sp. TSS-1 led to the isolation of three new polyketide derivatives, including one benzophenon derivative ( 1 ), two spirocyclic polyketides ( 4 and 5 ), along with four known compounds ( 2 , 3 , 6 and 7 ). Their structures and the absolute configurations were characterized by means of NMR, HRESIMS, 13 C NMR and theoretical electronic circular dichroism calculations. Furthermore, all compounds were evaluated for their antibacterial activity against four microbial pathogens ( Staphylococcus aureus , Enterococcus faecalis , Pseudomonas aeruginosa and Escherichia coli ), and compounds 1 , 2 , 3 and 5 displayed significant selective antibacterial activity against S. aureus with MIC values ranging from 3.9 to 7.8 µg/mL.

Two new chromone derivatives ( 1 and 2 ), and two known compounds ( 3 and 4 ) were isolated from the rhizosphere soil fungus Ilyonectria robusta . Their planar structures and absolute configurations were determined by extensive spectroscopic analysis and electronic circular dichroism (ECD) calculations. Additionally, all the isolated compounds were evaluated for their antibacterial activity against Staphylococcus aureus , Enterococcus faecalis , Pseudomonas aeruginosa and Escherichia coli , but no obvious activity was observed at a concentration of 128 μg/mL.

The Chinese tree shrew ( Tupaia belangeri chinensis ), a member of the mammalian order Scandentia, exhibits considerable similarities with primates, including humans, in aspects of its nervous, immune, and metabolic systems. These similarities have established the tree shrew as a promising experimental model for biomedical research on cancer, infectious diseases, metabolic disorders, and mental health conditions. Herein, we used meta-transcriptomic sequencing to analyze plasma, as well as oral and anal swab samples, from 105 healthy asymptomatic tree shrews to identify the presence of potential zoonotic viruses. In total, eight mammalian viruses with complete genomes were identified, belonging to six viral families, including Flaviviridae , Hepeviridae , Parvovirinae , Picornaviridae , Sedoreoviridae , and Spinareoviridae . Notably, the presence of rotavirus was recorded in tree shrews for the first time. Three viruses - hepacivirus 1, parvovirus, and picornavirus - exhibited low genetic similarity (<70%) with previously reported viruses at the whole-genome scale, indicating novelty. Conversely, three other viruses - hepacivirus 2, hepatovirus A and hepevirus - exhibited high similarity (>94%) to known viral strains. Phylogenetic analyses also revealed that the rotavirus and mammalian orthoreovirus identified in this study may be novel reassortants. These findings provide insights into the diverse viral spectrum present in captive Chinese tree shrews, highlighting the necessity for further research into their potential for cross-species transmission.

Human immunodeficiency virus-1 (HIV-1) infection can cause chronic activation, exhaustion, and anergy of the immune system. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is an immune checkpoint molecule, which plays an important role in immune homeostasis and disease. CTLA-4 expression is elevated in HIV-1-infected patients and is associated with disease progression. However, the mechanism controlling expression of CTLA-4 in HIV-1 infection is poorly characterized. In this study, we used a SIV-infected Chinese rhesus macaque (ChRM) model to explore CTLA-4 expression in SIV infection. Results showed that SIV infection significantly increased CTLA-4 expression in all T cell subsets, especially central memory T cells. CTLA-4+CD4+ T cell frequency was significantly associated with disease progression markers. Activation of the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling pathway regulated CTLA-4 expression in CD4+T cells, as confirmed by stimulation with dibutyryl cyclic adenosine monophosphate, forskolin, and 3-isobutyl-1-methylxanthine, and inhibition with H-89 ex vivo. Simultaneously, cAMP concentration in PBMCs and PKA activity in both PBMCs and CD4+ T cells were increased in acute SIV-infected ChRMs, accompanied by an increase in adenylate cyclase 6 expression and a decrease in cAMP-phosphodiesterase 3A (PDE3A), PDE4B, and PDE5A expression in PBMCs. In addition, selective inhibition of PDE4B and PDE5A activity enhanced CTLA-4 expression in CD4+ T cells. These results suggest that SIV infection alters cAMP metabolism and increases cAMP-PKA signaling pathway activation, which up-regulates the expression of CTLA-4 in acute SIVmac239-infected ChRMs. Thus, regulation of the cAMP-PKA signaling pathway may be a potential strategy for the restoration of T cell function and therapy for AIDS., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product service and/or company that could be construed as influencing the position presented in or the review of the manuscript entitle., (Copyright © 2024. Published by Elsevier B.V.)

Background: Hypertension is a prevalent cardiovascular disease characterized by elevated blood pressure and increased vascular resistance. HDAC inhibitors have emerged as potential therapeutic agents due to their ability to modulate gene expression and cellular processes. YPX-C-05, a novel hydroxamic acid-based HDAC inhibitor, shows promise in its vasodilatory effects and potential targets for hypertension treatment. In this study, we aimed to elucidate the mechanisms underlying YPX-C-05's vasodilatory effects and explore its therapeutic potential in hypertension., Methods: To determine the ex vivo vasodilatory effects of YPX-C-05, isolated aortic rings precontracted with phenylephrine were used. We assessed YPX-C-05's inhibitory effects on HDACs and its impact on histone H4 deacetylation levels in endothelial cells. Network pharmacology analysis was employed to predict putative targets of YPX-C-05 for hypertension treatment. To investigate the involvement of the PI3K/Akt/eNOS pathway, we employed enzyme-linked immunosorbent assay and to assess the levels of NO, ET-1, BH2, and BH4 in human umbilical vein endothelial cells. And we also analyzed the mRNA expression of eNOS and ET-1. Furthermore, Western blotting was conducted to quantify the phosphorylated and total Akt and eNOS levels in human umbilical vein endothelial cell lysates following treatment with YPX-C-05. In order to elucidate the vasodilatory mechanism of YPX-C-05, we employed pharmacological inhibitors for evaluation purposes. Furthermore, we evaluated the chronic antihypertensive effects of YPX-C-05 on N-omega-nitro-L-arginine-induced hypertensive mice in an in vivo model. Vascular remodeling was assessed through histological analysis., Results: Our findings demonstrated that YPX-C-05 exerts significant vasodilatory effects in isolated aortic rings precontracted with phenylephrine. Furthermore, YPX-C-05 exhibited inhibitory effects on HDACs and increased histone H4 acetylation in endothelial cells. Network pharmacology analysis predicted YPX-C-05 might activate endothelial eNOS via PI3K/Akt signaling pathway. Inhibition of the PI3K/Akt/eNOS pathway attenuated the vasodilatory effects of YPX-C-05, as evidenced by reduced levels of phosphorylated Akt and eNOS in human umbilical vein endothelial cell lysates. The chronic administration of YPX-C-05 in N-omega-nitro-L-arginine-induced hypertensive mice resulted in significant antihypertensive effects. Histological analysis demonstrated a reduction in vascular remodeling, further supporting the therapeutic potential of YPX-C-05 in hypertension., Conclusion: This study demonstrates for the first time that the novel hydroxamic acid-based HDAC inhibitor YPX-C-05 produces significant antihypertensive and vasodilatory effects through the PI3K/Akt/eNOS pathway. Our findings support the developing prospect of YPX-C-05 as a novel antihypertensive drug., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)

Members of the Flaviviridae family, encompassing the Flavivirus and Hepacivirus genera, are implicated in a spectrum of severe human pathologies. These diseases span a diverse spectrum, including hepatitis, vascular shock syndrome, encephalitis, acute flaccid paralysis, and adverse fetal outcomes, such as congenital heart defects and increased mortality rates. Notably, infections by Flaviviridae viruses have been associated with substantial cardiovascular compromise, yet the exploration into the attendant cardiovascular sequelae and underlying mechanisms remains relatively underexplored. This review aims to explore the epidemiology of Flaviviridae virus infections and synthesize their cardiovascular morbidities. Leveraging current research trajectories and our investigative contributions, we aspire to construct a cogent theoretical framework elucidating the pathogenesis of Flaviviridae -induced cardiovascular injury and illuminate prospective therapeutic avenues.

Angiotensin-converting enzyme 2 (ACE2) is a major cell entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The induction of ACE2 expression may serve as a strategy by SARS-CoV-2 to facilitate its propagation. However, the regulatory mechanisms of ACE2 expression after viral infection remain largely unknown. Using 45 different luciferase reporters, the transcription factors SP1 and HNF4α were found to positively and negatively regulate ACE2 expression, respectively, at the transcriptional level in human lung epithelial cells (HPAEpiCs). SARS-CoV-2 infection increased the transcriptional activity of SP1 while inhibiting that of HNF4α. The PI3K/AKT signaling pathway, activated by SARS-CoV-2 infection, served as a crucial regulatory node, inducing ACE2 expression by enhancing SP1 phosphorylation-a marker of its activity-and reducing the nuclear localization of HNF4α. However, colchicine treatment inhibited the PI3K/AKT signaling pathway, thereby suppressing ACE2 expression. In Syrian hamsters ( Mesocricetus auratus ) infected with SARS-CoV-2, inhibition of SP1 by either mithramycin A or colchicine resulted in reduced viral replication and tissue injury. In summary, our study uncovers a novel function of SP1 in the regulation of ACE2 expression and identifies SP1 as a potential target to reduce SARS-CoV-2 infection., Competing Interests: HH, RL, XL, LW, QZ, XT, RZ, YM, YZ, CZ No competing interests declared, (© 2024, Han, Luo, Long et al.)

The difunctionalization of alkenes-a process that installs two functional groups in a single operation and transforms chemical feedstocks into value-added products-is one of the most appealing synthetic methods in contemporary chemistry. However, the introduction of two distinct functional groups via two readily accessible nucleophiles remains a formidable challenge. Existing intermolecular alkene azidocyanation methods, which primarily focus on aryl alkenes and rely on stoichiometric chemical oxidants. We report herein an unprecedented electrochemical strategy for alkene azidocyanation that is compatible with both alkyl and aryl alkenes. This is achieved by harnessing the finely-tuned anodic electron transfer and the strategic selection of copper/ligand complexes. The reactions of aryl alkenes were rendered enantioselective by employing a chiral ligand. Crucially, the mild conditions and well-regulated electrochemical process assure exceptional tolerance for various functional groups and substrate compatibility with both terminal and internal alkyl alkenes., (© 2023 Wiley-VCH GmbH.)

Vaccines have been the primary remedy in the global fight against coronavirus disease 2019 (COVID-19). The receptor-binding domain (RBD) of the spike protein, a critical viral immunogen, is affected by the heterogeneity of its glycan structures and relatively low immunogenicity. Here, we describe a scalable synthetic platform that enables the precise synthesis of homogeneously glycosylated RBD, facilitating the elucidation of carbohydrate structure-function relationships. Five homogeneously glycosylated RBDs bearing biantennary glycans were prepared, three of which were conjugated to T-helper epitope (T pep ) from tetanus toxoid to improve their weak immune response. Relative to natural HEK293-derived RBD, synthetic RBDs with biantennary N -glycan elicited a higher level of neutralising antibodies against SARS-CoV-2 in mice. Furthermore, RBDs containing T pep elicited significant immune responses in transgenic mice expressing human angiotensin-converting enzyme 2. Our collective data suggest that trimming the N -glycans and T pep conjugation of RBD could potentially serve as an effective strategy for developing subunit vaccines providing efficient protection., (© The Author(s) 2024. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

Aureoboletus raphanaceus is a member of boletoid mushroom, which is named after its distinctive radish smell. The mitochondrial genome and phylogenetic relationships with other boletes need to be investigated to gain a comprehensive understanding of it. In this study, we sequenced the mitochondrial genome of A. raphanaceus using next-generation sequencing technology and found that its mitochondrial genome is a circular DNA molecule measuring 42,157 bp. It consists of 15 core protein-coding genes, 27 transfer RNA genes, and two ribosomal RNA genes. The mitochondrial genome had a base composition of A (39.89%), C (11.06%), G (11.67%), and T (37.38%), with a GC content of 22.73%. A phylogenetic tree based on 22 mitochondrial genomes was constructed, which provided the first insights into the phylogenetic relationships of this species with related boletes., Competing Interests: The authors have declared that no competing interests exist., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

The RNA-dependent RNA polymerase (RdRp) is a crucial element in the replication and transcription of RNA viruses. Although the RdRps of lethal human coronaviruses severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV) have been extensively studied, the molecular mechanism of the catalytic subunit NSP12, which is involved in pathogenesis, remains unclear. In this study, the biochemical and cell biological results demonstrate the interactions between SARS-CoV-2 NSP12 and seven host proteins, including three splicing factors (SLU7, PPIL3, and AKAP8). The entry efficacy of SARS-CoV-2 considerably decreased when SLU7 or PPIL3 was knocked out, indicating that abnormal splicing of the host genome was responsible for this occurrence. Furthermore, the polymerase activity and stability of SARS-CoV-2 RdRp were affected by the three splicing factors to varying degrees. In addition, NSP12 and its homologues from SARS-CoV and MERS-CoV suppressed the alternative splicing of cellular genes, which were influenced by the three splicing factors. Overall, our research illustrates that SARS-CoV-2 NSP12 can engage with various splicing factors, thereby impacting virus entry, replication, and gene splicing. This not only improves our understanding of how viruses cause diseases but also lays the foundation for the development of antiviral therapies., (© 2024 Wiley Periodicals LLC.)

Bromodomain-containing protein 4 (BRD4) inhibitors have been proven to be a promising option for anti-HIV-1 latency therapeutics. We herein describe the design, synthesis, and anti-HIV-1 latency bioevaluation of triazolopyridine derivatives as BRD4 inhibitors. Among them, compound 13d displayed favorable HIV-1 reactivation and prominent safety profile without triggering abnormal immune activation. It exerted strong synergism when combined with the PKC activator prostratin and has the same BRD4-targeting latency mechanism as observed with JQ1, by stimulating Tat-dependent HIV-1 elongation. Besides, it neither affected the antiviral efficacies of antiviral drugs nor caused secondary infections to uninfected cells and the latency reversing potency of 13d , in turn, was not affected by different classes of antiviral drugs., Competing Interests: The authors declare no competing financial interest., (© 2023 American Chemical Society.)

Introduction: Activated microglia can be polarized to the pro-inflammatory M1 phenotype and the anti-inflammatory M2 phenotype. Low-intensity pulsed ultrasound (LIPUS) can attenuate pro-inflammatory responses in activated microglia., Objective: This study aimed to investigate the effects of LIPUS on M1/M2 polarization of microglial cells and the regulatory mechanisms associated with signaling pathways., Methods: BV-2 microglial cells were stimulated by lipopolysaccharide (LPS) to an M1 phenotype or by interleukin-4 (IL-4) to an M2 phenotype. Some microglial cells were exposed to LIPUS, while others were not. M1/M2 marker mRNA and protein expression were measured using real-time polymerase chain reaction and western blot, respectively. Immunofluorescence staining was performed to determine inducible nitric oxide synthase (iNOS)-/arginase-1 (Arg-1)- and CD68-/CD206-positive cells., Results: LIPUS treatment significantly attenuated LPS-induced increases in inflammatory markers (iNOS, tumor necrosis factor-α, interleukin-1β, and interleukin-6) as well as the expression of cell surface markers (CD86 and CD68) of M1-polarized microglia. In contrast, LIPUS treatment significantly enhanced the expression of M2-related markers (Arg-1, IL-10, and Ym1) and membrane protein (CD206). LIPUS treatment prevented M1 polarization of microglia and enhanced or sustained M2 polarization by regulating M1/M2 polarization through the signal transducer and activator of transcription 1/STAT6/peroxisome proliferator-activated receptor gamma pathways., Conclusions: Our findings suggest that LIPUS inhibits microglial polarization and switches microglia from the M1 to the M2 phenotype., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Liver fibrosis (LF) is an important reparative process in response to acute or chronic hepatic injury, which has the potential to advance towards cirrhosis and hepatocellular carcinoma. Dietary naringin consumption contributes to protection against LF in animal studies, while the exact protective mechanism of naringin remains unclear. This study aimed to investigate the molecular mechanisms behind the potential protective effect of naringin against TAA-induced LF in zebrafish. In this study, we utilized zebrafish to create the LF model and investigate the therapeutic mechanism of naringin. Firstly, we evaluated the changes in hepatic fibrosis and lipid accumulation in the liver following naringin treatment with oil red O, Nile red, and Sirius red and immunohistochemistry. In addition, we employed an ROS probe to directly measure oxidative stress and monitor inflammatory cell migration in a zebrafish transgenic line. Morpholino was used in the knockdown of IDO1 in order to verify its vital role in LF. Our findings demonstrated that naringin exhibited anti-inflammatory and anti-fibrotic action in conjunction with a reversal in lipid accumulation, oxidative stress and suppression of macrophage infiltration and activation of hepatic stellate cells. Furthermore, the results showed that the antifibrotic effect of naringin was removed upon IDO1 knockdown, proving that naringin exerts a protective effect by regulating IDO1. Naringin demonstrates remarkable protective effects against LF, effectively counteracting inflammation and hepatic steatosis in zebrafish liver. These findings suggest that naringin may function as an effective IDO1 inhibitor, holding the potential for clinical translation as a therapeutic agent for the treatment of LF.

Photocatalytic organic reactions, harvesting solar energy to produce high value-added organic chemicals, have attracted increasing attention as a sustainable approach to address the global energy crisis and environmental issues. Reticular framework materials, including metal-organic frameworks (MOFs) and covalent organic frameworks (COFs), are widely considered as promising candidates for photocatalysis owing to their high crystallinity, tailorable pore environment and extensive structural diversity. Although the design and synthesis of MOFs and COFs have been intensively developed in the last 20 years, their applications in photocatalytic organic transformations are still in the preliminary stage, making their systematic summary necessary. Thus, this review aims to provide a comprehensive understanding and useful guidelines for the exploration of suitable MOF and COF photocatalysts towards appropriate photocatalytic organic reactions. The commonly used reactions are categorized to facilitate the identification of suitable reaction types. From a practical viewpoint, the fundamentals of experimental design, including active species, performance evaluation and external reaction conditions, are discussed in detail for easy experimentation. Furthermore, the latest advances in photocatalytic organic reactions of MOFs and COFs, including their composites, are comprehensively summarized according to the actual active sites, together with the discussion of their structure-property relationship. We believe that this study will be helpful for researchers to design novel reticular framework photocatalysts for various organic synthetic applications.

One new cyclopeptide, cyclo-( L -Trp- L -Phe- L -Phe) ( 1 ), one new 2-pyridone derivative, fusarone A ( 3 ), and one new natural indole derivative, ethyl 3-indoleacetate ( 4 ), along with six known compounds were isolated from the endophytic fungus Fusarium proliferatum T2-10. The planar structures of three new compounds were identified by spectral methods including 1D and 2D NMR techniques, and the absolute configuration of compound 1 was elucidated by Marfey-MS method. In addition, all compounds were evaluated for their cytotoxic and antibacterial activities in vitro . Compound 2 showed remarkable cytotoxic activities against two human hepatoma cell lines SMMC7721 and HepG2 with IC 50 values of 5.89 ± 0.74 and 6.16 ± 0.52 μM, and showed moderate antibacterial activities against Staphylococcus aureus and Enterococcus faecalis with MIC values of 7.81 and 15.62 μg/mL, respectively.

Background: The use of Anti-PD-1 therapy has yielded promising outcomes in hepatocellular carcinoma (HCC). However, limited research has been conducted on the overall survival (OS) of patients with varying tumor responses and treatment duration., Methods: This retrospective study analyzed HCC patients who received sintilimab between January 2019 and December 2020 at four centers in China. The evaluation of tumor progression was based on Response Evaluation Criteria in Solid Tumors version 1.1. The study investigated the correlation between tumor response and OS, and the impact of drug use on OS following progressive disease (PD)., Results: Out of 441 treated patients, 159 patients satisfied the inclusion criteria. Among them, 77 patients with disease control exhibited a significantly longer OS compared to the 82 patients with PD (median OS 26.0 vs. 11.3 months, P < 0.001). Additionally, the OS of patients with objective response (OR) was better than that of patients with stable disease (P = 0.002). Among the 47 patients with PD who continued taking sintilimab, the OS was better than the 35 patients who discontinued treatment (median OS 11.4 vs. 6.9 months, P = 0.042)., Conclusions: In conclusion, the tumor response in HCC patients who received sintilimab affects OS, and patients with PD may benefit from continued use of sintilimab., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Lanmaoa macrocarpa is a boletoid mushroom from the family Boletaceae and was named after its relatively larger basidiocarp and bluish color change when bruised. At present, its mitochondrial genome and phylogenetic relationships with other boletes remain unexplored. In this study, we sequenced the mitochondrial genome of L. macrocarpa using next-generation sequencing technology and found that its mitochondrial genome, a circular DNA molecule of 38,139 bp, comprised 15 core protein-coding genes, 26 transfer RNA genes and two ribosomal RNA genes. The mitochondrial genome had a base composition of A (37.05%), C (12.08%), G (11.42%) and T (39.45%) with a GC content of 23.50%. A phylogenetic tree based on 20 mitochondrial genomes was constructed, which revealed the phylogenetic relationships of this species with related boletes for the first time., Competing Interests: The authors have declared that no competing interests exist., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

According to the Global Antimicrobial Resistance and Use Surveillance System (GLASS) data, antibiotic resistance escalates more challenges in treatment against communicable diseases worldwide. Henceforth, the use of combinational antimicrobial therapy and metal-conjugated phytoconstituents composites are considered as alternatives. The present study explored the efficacy of mercuric-sulfide-based metallopharmaceutical, Sivanar Amirtham for anti-bacterial, anti-tuberculosis, anti-HIV therapeutics and toxicity profile by haemolytic assay, first of its kind. The anti-bacterial study was performed against both gram-positive and gram-negative pathogens including Staphylococcus aureus (ATCC 29213), Methicillin-resistant Staphylococcus aureus (MRSA: ATCC 43300), Enterococcus faecalis (ATCC 29212), Pseudomonas aeruginosa (PA14) and Vibrio cholerae (MTCC 3905) by agar well diffusion assay, wherein the highest zone of inhibition was identified for MRSA (20.7 mm) and V. cholerae (34.3 mm) at 25 mg/mL. Furthermore, the anti-tuberculosis activity experimented by microtitre alamar blue assay against M. tuberculosis (ATCC 27294) demonstrated significant activity at the concentration range of 12.5-100 µg/mL. Additionally, the anti-HIV efficacy established by the syncytia inhibition method using C8166 cell lines infected with HIV-1 IIIB , showed a significant therapeutic effect. The in-vitro toxicity assay proved Sivanar Amirtham to be non-haemolytic and haemocompatible. The physicochemical characterization studies revealed the nano-sized particles with different functional groups and the distinctive metal-mineral complex could be attributed to the multi-site targeting ability. The rationale evidence and scientific validation for the efficacy of Sivanar Amirtham ensures that it could be proposed as an alternative or adjuvant for both prophylactics and therapeutics to overcome HIV infection and antimicrobial resistance as well as the multi-drug resistance challenges., (© 2023. Springer Nature Limited.)

Developing chiral receptors with an endo-functionalized cavity for chiral recognition is of great significance in the field of molecular recognition. This study presents two pairs of chiral naphthotubes containing a bis-thiourea endo-functionalized cavity. Each chiral naphthotube has two homochiral centers which were fixed adjacent to the thiourea groups, causing the skeleton and thiourea groups to twist enantiomerically through chiral transfer. These chiral naphthotubes are highly effective at enantiomerically recognizing various neutral chiral molecules with an enantioselectivity up to 17.0. Furthermore, the mechanism of the chiral recognition has been revealed to be originated from differences in multiple non-covalent interactions. Various factors, such as the shape of cavities, substituents of guests, flexibility of host and binding modes are demonstrated to contribute to creating differences in the non-covalent interactions. Additionally, the driving force behind enantioselectivity is mainly attributed to enthalpic differences, and enthalpy -entropy compensation has also been observed to influence enantioselectivity., (© 2023. Springer Nature Limited.)

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by the SFTS virus (SFTSV) and with a high fatality rate. Thrombocytopenia is a major clinical manifestation observed in SFTS patients, but the underlying mechanism remains largely unclear. Here, we explored the effects of SFTSV infection on platelet function in vivo in severely infected SFTSV IFNar -/- mice and on mouse and human platelet function in vitro. Results showed that SFTSV-induced platelet clearance acceleration may be the main reason for thrombocytopenia. SFTSV-potentiated platelet activation and apoptosis were also observed in infected mice. Further investigation showed that SFTSV infection induced platelet reactive oxygen species (ROS) production and mitochondrial dysfunction. In vitro experiments revealed that administration of SFTSV or SFTSV glycoprotein (Gn) increased activation, apoptosis, ROS production, and mitochondrial dysfunction in separated mouse platelets, which could be effectively ameliorated by the application of antioxidants (NAC (N-acetyl-l-cysteine), SKQ1 (10-(6'-plastoquinonyl) decyltriphenylphosphonium) and resveratrol). In vivo experiments showed that the antioxidants partially rescued SFTSV infection-induced thrombocytopenia by improving excessive ROS production and mitochondrial dysfunction and down-regulating platelet apoptosis and activation. Furthermore, while SFTSV and Gn directly potentiated human platelet activation, it was completely abolished by antioxidants. This study revealed that SFTSV and Gn can directly trigger platelet activation and apoptosis in an ROS-MAPK-dependent manner, which may contribute to thrombocytopenia and hemorrhage during infection, but can be abolished by antioxidants., Competing Interests: Declaration of competing interest All authors declare that there are no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Aim: Inflammatory bowel disease (IBD) may be a risk factor in the development of brain inflammation. It has been demonstrated noninvasive neuromodulation through sub-organ ultrasound stimulation. The purpose of this study was to investigate whether abdominal low-intensity pulsed ultrasound (LIPUS) alleviates lipopolysaccharide (LPS)-induced cortical inflammation via inhibition of colonic inflammation., Materials and Methods: Colonic and cortical inflammation was induced in mice by LPS (0.75 mg/kg, i.p. injection) for 7 days, followed by application of LIPUS (0.5 and 1.0 W/cm 2 ) to the abdominal area for 6 days. Biological samples were collected for Western blot analysis, gelatin zymography, colon length measurement, and histological evaluation., Key Findings: LIPUS treatment significantly attenuated LPS-induced increases in IL-6, IL-1β, COX-2, and cleaved caspase-3 expression in the colon and cortex of mice. Moreover, LIPUS significantly increased the levels of tight junction proteins in the epithelial barrier in the mouse colon and cortex with LPS-induced inflammation. Compared to the group treated only with LPS, the LIPUS-treated groups showed decreased muscle thickness and increased crypt length and colon length. Furthermore, LIPUS treatment reduced inflammation by inhibiting the LPS-induced activation of TLR4/NF-κB inflammatory signaling in the brain., Significance: We found that LIPUS alleviated LPS-induced colonic and cortical inflammation through abdominal stimulation of mice. These results suggest that abdominal LIPUS stimulation may be a novel therapeutic strategy against neuroinflammation via enhancement of tight junction protein levels and inhibition of inflammatory responses in the colon., Competing Interests: Declaration of competing interest All authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Cadmium pollution in Moso bamboo forests poses a potential threat to the sustainable development of the bamboo industry. However, the effects of cadmium toxicity on Moso growth and its mechanisms of adaptation to cadmium stress are poorly understood. In this study, the physiological and transcriptional response of Moso to cadmium stress was investigated in detail using Moso seedlings in a hydroponic system. Cadmium toxicity severely inhibited the growth of roots but had little effect on biomass accumulation in the aerial parts. Cadmium accumulation in roots and aerial parts increased as external cadmium increased, with cadmium mainly localized in the epidermis and pericycle cells in the roots. The uptake and root-to-shoot translocation of cadmium was stimulated, but the photosynthetic process was suppressed under cadmium stress. A total of 3469 differentially expressed genes were identified from the transcriptome profile and those involved in cadmium uptake, transportation and detoxification were analyzed as candidates for having roles in adaptation to cadmium stress. The results suggested that Moso is highly efficient in cadmium uptake, xylem loading and translocation, as well as having a high capacity for cadmium accumulation. This work also provided basic information on physiological and transcriptional responses of Moso to cadmium toxicity., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Inflammatory bowel disease (IBD) is characterized by chronic inflammation in the intestinal tract. There is currently no effective cure for IBD. The aim of this study was to evaluate the protective effect of low-intensity pulsed ultrasound (LIPUS) on lipopolysaccharide (LPS)-induced intestinal damage in a C57BL/6 mouse model. Colonic inflammation was induced by LPS injection (0.75 mg/kg, i.p.) for 7 days. A 1.0 MHz ultrasound transducer was used with a duty cycle of 5% and a repetition frequency of 1 Hz. LIPUS was applied to the abdominal region for 15 min/day from days 1 to 6 at both intensity of 0.5 W/cm 2 or 1.0 W/cm 2 . Colonic samples were collected for macroscopic and westerm blotting analysis. First, the optimal dose of LPS for experiments was investigated. Our results demonstrated that LIPUS alleviates colonic damage by reducing colon shortening and increasing the levels of tight junction proteins such as Occludin and ZO-1. These findings show that abdominal LIPUS stimulation may be a novel therapeutic strategy for IBD through enhancement of tight junction protein levels and attenuation of colonic length.

Background: Gynecological cancer will become a more important public health problem in future years but limited evidence on gynecological cancer burden in China., Methods: We extracted age-specific rate of cancer cases and deaths during 2007-2016 from the Chinese Cancer Registry Annual Report, and estimated age-specific population size using the data released by National Bureau of Statistics of China. Cancer burden were calculated by multiplying the rates with the population size. Temporal trends of the cancer cases, incidence, deaths, and mortality during 2007-2016 were calculated by JoinPoint Regression Program, and from 2017 to 2030 were projected by grey prediction model GM (1,1)., Results: In China, total gynecological cancer cases increased from 177,839 to 241,800, with the average annual percentage change of 3.5% (95% CI: 2.7-4.3%) during 2007-2016. Cervical, uterine, ovarian, vulva, and other gynecological cancer cases increased by 4.1% (95% CI: 3.3-4.9%), 3.3% (95% CI: 2.6-4.1%), 2.4% (95% CI: 1.4-3.5%), 4.4% (95% CI: 2.5-6.4%), and 3.6% (95% CI: 1.4-5.9%) respectively. From 2017 to 2030, projected gynecological cancer cases are changing from 246,581 to 408,314. Cervical, vulva and vaginal cancers showed evident upward trend, while uterine and ovarian cancer cases are slightly increasing. The increases for age-standardized incidence rates were similar with that of cancer cases. Temporal trends of cancer deaths and mortality were similar with that of cancer cases and incidence during 2007-2030, except that uterine cancer deaths and mortality were declined., Conclusions: With the aging of population and other increased risk factors, the burden of gynecological cancers in China is likely to be grew rapidly in the future, comprehensive gynecological cancer control should be concerned., (© 2023. The Author(s).)

Objective: This study aimed to investigate the relationship between the TyG (Triglyceride-glucose index) and the prognosis of patients with HOCM (hypertrophic obstructive cardiomyopathy) without diabetes., Research Design and Methods: A total of 713 eligible patients with HOCM were enrolled in this study and divided into two groups based on treatment: an invasive treatment group (n = 461) and a non-invasive treatment group (n = 252). The patients in both two groups were then divided into three groups based on their TyG index levels. The primary endpoints of this study were Cardiogenic death during long-term follow-up. Kaplan-Meier analysis was used to study the cumulative survival of different groups. Restricted cubic spline was used to model nonlinear relationships between the TyG index and primary endpoints. Myocardial perfusion imaging/Myocardial metabolic imaging examinations were performed to assess glucose metabolism in the ventricular septum of the HOCM patients., Results: The follow-up time of this study was 41.47 ± 17.63 months. The results showed that patients with higher TyG index levels had better clinical outcomes (HR, 0.215; 95% CI 0.051,0.902; P = 0.036, invasive treatment group; HR, 0.179; 95% CI 0.063,0.508; P = 0.001, non-invasive treatment group). Further analysis showed that glucose metabolism in the ventricular septum was enhanced in HOCM patients., Conclusions: The findings of this study suggest that the TyG index may serve as a potential protective factor for patients with HOCM without diabetes. The enhanced glucose metabolism in the ventricular septum of HOCM patients may provide a potential explanation for the relationship between the TyG index and HOCM prognosis., (© 2023. The Author(s).)

Some people remain healthier throughout life than others but the underlying reasons are poorly understood. Here we hypothesize this advantage is attributable in part to optimal immune resilience (IR), defined as the capacity to preserve and/or rapidly restore immune functions that promote disease resistance (immunocompetence) and control inflammation in infectious diseases as well as other causes of inflammatory stress. We gauge IR levels with two distinct peripheral blood metrics that quantify the balance between (i) CD8 +  and CD4 +  T-cell levels and (ii) gene expression signatures tracking longevity-associated immunocompetence and mortality-associated inflammation. Profiles of IR metrics in ~48,500 individuals collectively indicate that some persons resist degradation of IR both during aging and when challenged with varied inflammatory stressors. With this resistance, preservation of optimal IR tracked (i) a lower risk of HIV acquisition, AIDS development, symptomatic influenza infection, and recurrent skin cancer; (ii) survival during COVID-19 and sepsis; and (iii) longevity. IR degradation is potentially reversible by decreasing inflammatory stress. Overall, we show that optimal IR is a trait observed across the age spectrum, more common in females, and aligned with a specific immunocompetence-inflammation balance linked to favorable immunity-dependent health outcomes. IR metrics and mechanisms have utility both as biomarkers for measuring immune health and for improving health outcomes., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Tripartite motif-containing protein 5α (TRIM5α) is generally known to block the postentry events of HIV-1. Here, we report an uncharacterized role for TRIM5α in the maintenance of viral latency. Knockdown of TRIM5α potentiates the transcription of HIV-1 in multiple latency models, which is reversed by shRNA-resistant TRIM5α. TRIM5α suppresses TNFα-activated HIV-1 LTR-driven as well as NF-κB- and Sp1-driven gene expression, with the RING and B-box 2 domains being the essential determinants. Mechanistically, TRIM5α binds to and enhances the recruitment of histone deacetylase 1 (HDAC1) to NF-κB p50 and Sp1. ChIP‒qPCR analyses further reveal that the association of TRIM5α with HIV-1 LTR induces HDAC1 recruitment and local H3K9 deacetylation. Conserved suppression effects of TRIM5α orthologs from multiple species on both HIV-1 and endo-retroelement HERV-K LTR activities have also been demonstrated. These findings provide new insights into the molecular mechanisms by which proviral latency is initially established and activatable proviruses are resilenced by histone deacetylase recruitment., (© 2023. The Author(s).)