[Traditional Chinese medicine preparations in medical institutions: current situation and inspirations on research and development of new traditional Chinese medicine preparations].

Traditional Chinese medicine(TCM) preparations in medical institutions embody the characteristics of TCM and are the source for the development of new TCM drugs. This study summarizes the current situation, existing problems, and development trends of the TCM preparations in medical institutions in 31 provinces across China. Furthermore, this paper puts forward the development path of new TCM preparations based on the requirements of registration and management regulations of TCM preparations, providing new ideas for promoting the inheritance, innovation, and development of TCM.

Pirin Promotes the Progression of Non-Small-Cell Lung Cancer by Increasing ODC1 to Suppress Autophagy.

Non-small-cell lung cancer (NSCLC), a common malignant tumor, requires deeper pathogenesis investigation. Autophagy is an evolutionarily conserved lysosomal degradation process that is frequently blocked during cancer progression. It is an urgent need to determine the novel autophagy-associated regulators in NSCLC. Here, we found that pirin was upregulated in NSCLC, and its expression was positively correlated with poor prognosis. Overexpression of pirin inhibited autophagy and promoted NSCLC proliferation. We then performed data-independent acquisition-based quantitative proteomics to identify the differentially expressed proteins (DEPs) in pirin-overexpression (OE) or pirin-knockdown (KD) cells. Among the pirin-regulated DEPs, ornithine decarboxylase 1 (ODC1) was downregulated in pirin-KD cells while upregulated along with pirin overexpression. ODC1 depletion reversed the pirin-induced autophagy inhibition and pro-proliferation effect in A549 and H460 cells. Immunohistochemistry showed that ODC1 was highly expressed in NSCLC cancer tissues and positively related with pirin. Notably, NSCLC patients with pirinhigh/ODC1high had a higher risk in terms of overall survival. In summary, we identified pirin and ODC1 as a novel cluster of prognostic biomarkers for NSCLC and highlighted the potential oncogenic role of the pirin/ODC1/autophagy axis in this cancer type. Targeting this pathway represents a possible therapeutic approach to treat NSCLC.

Chronic SIV-Induced neuroinflammation disrupts CCR7+ CD4+ T cell immunosurveillance in the rhesus macaque brain.

CD4+ T cells survey and maintain immune homeostasis in the brain, yet their differentiation states and functional capabilities remain unclear. Our approach, combining single-cell transcriptomic analysis, ATAC-Seq, spatial transcriptomics, and flow cytometry, revealed a distinct subset of CCR7+ CD4+ T cells resembling lymph node central memory (TCM) cells. We observed chromatin accessibility at the CCR7, CD28, and BCL-6 loci, defining molecular features of TCM. Brain CCR7+ CD4+ T cells exhibited recall proliferation and interleukin-2 production ex vivo, showcasing their functional competence. We identified the skull bone marrow as a local niche for these cells alongside CNS border tissues. Sequestering TCM cells in lymph nodes using FTY720 led to reduced CCR7+ CD4+ T cell frequencies in the cerebrospinal fluid, accompanied by increased monocyte levels and soluble markers indicating immune activation. In macaques chronically infected with SIVCL757 and experiencing viral rebound due to cessation of antiretroviral therapy, a decrease in brain CCR7+ CD4+ T cells was observed, along with increased microglial activation and initiation of neurodegenerative pathways. Our findings highlight a role for CCR7+ CD4+ T cells in CNS immune surveillance, and their decline during chronic SIV highlights their responsiveness to neuroinflammation.

Mussel-inspired polydopamine-modified biochar microsphere for reinforcing polylactic acid composite films: Emphasizing the achievement of excellent thermal and mechanical properties.

Having poor interfacial compatibility between biochar microsphere (BM) and polylactic acid (PLA) should be responsible for the unbalance of composite film strength and toughness. Elucidating the effect of polydopamine (PDA) on BM and BM/PLA composite films is the ultimate goal of this study based on the mussel bionic principle. It was found that the strong adhesion of PDA on the BM surface was achieved, which improved the surface roughness and thermal stability. Also, PDA modification can facilitate crystallization, increase thermal properties, improve interfacial compatibility, and enhance the tensile properties of BM/PLA composite films. Silane-based PDA modified BM/PLA composite film exhibited the best tensile strength, tensile modulus, and elongation at break with 77.95 MPa, 1.87 GPa, and 7.30%. These noteworthy findings, achieving a simultaneous improvement in PLA strength and toughness, hold promising implications for its sustainability.

Vaccine-Boosted CCP Decreases Virus Replication and Hastens Resolution of Infection Despite Transiently Enhancing Disease in SARS-CoV-2-Infected Hamsters.

Definitive data demonstrating the utility of coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) for treating immunocompromised patients remains elusive. To better understand the mechanism of action of CCP, we studied viral replication and disease progression in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected hamsters treated with CCP obtained from recovered COVID-19 patients that were also vaccinated with an mRNA vaccine, hereafter referred to as Vaxplas. Vaxplas transiently enhanced disease severity and lung pathology in hamsters treated near peak viral replication due to immune complex and activated complement deposition in pulmonary endothelium, and recruitment of M1 proinflammatory macrophages into the lung parenchyma. However, aside from one report, transient enhanced disease has not been reported in CCP recipient patients, and the transient enhanced disease in Vaxplas hamsters may have been due to mismatched species IgG-FcR interactions, infusion timing, or other experimental factors. Despite transient disease enhancement, Vaxplas dramatically reduced virus replication in lungs and improved infection outcome in SARS-CoV-2-infected hamsters.

Comparison of effectiveness and cost of different HCV testing strategies in high-risk populations in China.

High-risk populations are the predominant populations affected by hepatitis C virus (HCV) infection, and there is an urgent need for efficient and cost-effective HCV testing strategies for high-risk populations to identify potential undiagnosed HCV-infected individuals. This study compared several commonly used testing strategies and conducted effectiveness and cost analysis to select the appropriate testing strategy for diagnosing HCV infection in high-risk populations. Among the 2093 samples from high-risk populations in this study, 1716 were HCV negative, 237 were current HCV infection, 137 were past HCV infection, and three were acute early HCV infection. It was found that out of 237 patients with HCV current infection, Strategy A could detect 225 cases, with a missed detection rate of 5.06%, and the total cost was 33 299 RMB. In addition, Strategy B could detect 237 cases of current HCV infection, and the HCV missed detection rate was 0.00%, and the total cost was 147 221 RMB. While 137 cases of past HCV infection could be distinguished by strategy C, but 14 cases with current HCV infection were missed, with an HCV-positive missed detection rate of 5.91%, and the total cost for Strategy C was 43 059 RMB. In conclusion, in high-risk populations, the HCV positivity rate is typically higher. If feasible, the preferred approach is to directly conduct HCV RNA testing, which effectively minimizes the risk of missing cases. However, in situations with limited resources, it is advisable to initially choose a highly sensitive method for anti-HCV screening, followed by HCV RNA testing on reactive samples.

Deep analysis of CD4 T cells in the rhesus CNS during SIV infection.

Virologic suppression with antiretroviral therapy (ART) has significantly improved health outcomes for people living with HIV, yet challenges related to chronic inflammation in the central nervous system (CNS)-known as Neuro-HIV- persist. As primary targets for HIV-1 with the ability to survey and populate the CNS and interact with myeloid cells to co-ordinate neuroinflammation, CD4 T cells are pivotal in Neuro-HIV. Despite their importance, our understanding of CD4 T cell distribution in virus-targeted CNS tissues, their response to infection, and potential recovery following initiation of ART remain limited. To address these gaps, we studied ten SIVmac251-infected rhesus macaques using an ART regimen simulating suboptimal adherence. We evaluated four macaques during the acute phase pre-ART and six during the chronic phase. Our data revealed that HIV target CCR5+ CD4 T cells inhabit both the brain parenchyma and adjacent CNS tissues, encompassing choroid plexus stroma, dura mater, and the skull bone marrow. Aligning with the known susceptibility of CCR5+ CD4 T cells to viral infection and their presence within the CNS, high levels of viral RNA were detected in the brain parenchyma and its border tissues during acute SIV infection. Single-cell RNA sequencing of CD45+ cells from the brain revealed colocalization of viral transcripts within CD4 clusters and significant activation of antiviral molecules and specific effector programs within T cells, indicating CNS CD4 T cell engagement during infection. Acute infection led to marked imbalance in the CNS CD4/CD8 ratio which persisted into the chronic phase. These observations underscore the functional involvement of CD4 T cells within the CNS during SIV infection, enhancing our understanding of their role in establishing CNS viral presence. Our findings offer insights for potential T cell-focused interventions while underscoring the challenges in eradicating HIV from the CNS, particularly in the context of sub-optimal ART.

The fairness of shared responsibility for embodied carbon emission: a case study of the Yellow River Basin, China.

Under the dual constraints of China's carbon peaking and carbon neutrality goals, as well as ecological protection and high-quality development of the Yellow River Basin, clarifying the embodied carbon emissions and responsibility sharing of inter-provincial trade is crucial to the carbon reduction strategy of the Yellow River Basin. This paper uses the MRIO (multi-regional input-output) model to measure the production-side and consumption-side responsibility sharing of nine provinces in the Yellow River Basin in 2012 and 2017, revealing the amount and direction of the embodied carbon transfer between provinces, and finally introduces the share of provincial value added as the responsibility sharing factor to compare and analyze the differences between the three responsibility sharing methods. The results show the following: (1) The embodied carbon emissions on the production side in most provinces of the Yellow River Basin were larger than that on the consumption side, with the most significant differences in Shanxi, Inner Mongolia, and Shandong, among which local demand carbon emissions and intermediate product transfer out of carbon emissions were the main causes of production-side carbon emissions. (2) In general, all provinces except Shaanxi were net carbon transfer-in regions, and the embodied carbon was mainly transferred to Beijing, Jiangsu, Guangdong, Zhejiang, and Hebei. (3) Shared responsibility for carbon emissions was jointly determined by the volume of embodied carbon trade and the ability to obtain value added, which lay between production and consumption side responsibility shares. (4) The Yellow River Basin had a large responsibility-sharing factor and embodied carbon trade, and thus needs to take more responsibility for emission reduction. This study is expected to provide scientific support for the strategy of differentiated emission reduction in the Yellow River Basin and enrich the regional carbon accounting methods.

Corrigendum: Zilucoplan, a macrocyclic peptide inhibitor of human complement component 5, uses a dual mode of action to prevent terminal complement pathway activation.

[This corrects the article DOI: 10.3389/fimmu.2023.1213920.].

CD4 T cell Responses in the CNS during SIV infection.

Virologic suppression with antiretroviral therapy (ART) has significantly improved health outcomes for people living with HIV, yet challenges related to chronic inflammation in the central nervous system (CNS) - known as Neuro-HIV- persist. As primary targets for HIV-1 with the ability to survey and populate the CNS and interact with myeloid cells to co-ordinate neuroinflammation, CD4 T cells are pivotal in Neuro-HIV. Despite their importance, our understanding of CD4 T cell distribution in virus-targeted CNS tissues, their response to infection, and potential recovery following initiation of ART remain limited. To address these gaps, we studied ten SIVmac251-infected rhesus macaques using an ART regimen simulating suboptimal adherence. We evaluated four macaques during the acute phase pre-ART and six during the chronic phase. Our data revealed that HIV target CCR5+ CD4 T cells inhabit both the brain parenchyma and adjacent CNS tissues, encompassing choroid plexus stroma, dura mater, and the skull bone marrow. Aligning with the known susceptibility of CCR5+ CD4 T cells to viral infection and their presence within the CNS, high levels of viral RNA were detected in the brain parenchyma and its border tissues during acute SIV infection. Single-cell RNA sequencing of CD45+ cells from the brain revealed colocalization of viral transcripts within CD4 clusters and significant activation of antiviral molecules and specific effector programs within T cells, indicating CNS CD4 T cell engagement during infection. Despite viral suppression with ART, acute infection led to significant depletion of CNS CD4 T cells, persisting into the chronic phase. These findings underscore the functional involvement of CD4 T cells within the CNS during SIV infection, enhancing our understanding of their role in establishing CNS viral presence. Our results offer insights for potential T cell-focused interventions while also underscoring the challenges in eradicating HIV from the CNS, even with effective ART.

Administration of vaccine-boosted COVID-19 convalescent plasma to SARS-CoV-2 infected hamsters decreases virus replication in lungs and hastens resolution of the infection despite transiently enhancing disease and lung pathology.

The utility of COVID-19 convalescent plasma (CCP) for treatment of immunocompromised patients who are not able to mount a protective antibody response against SARS-CoV-2 and who have contraindications or adverse effects from currently available antivirals remains unclear. To better understand the mechanism of protection in CCP, we studied viral replication and disease progression in SARS-CoV-2 infected hamsters treated with CCP plasma obtained from recovered COVID patients that had also been vaccinated with an mRNA vaccine, hereafter referred to as Vaxplas. We found that Vaxplas dramatically reduced virus replication in the lungs and improved infection outcome in SARS-CoV-2 infected hamsters. However, we also found that Vaxplas transiently enhanced disease severity and lung pathology in treated animals likely due to the deposition of immune complexes, activation of complement and recruitment of increased numbers of macrophages with an M1 proinflammatory phenotype into the lung parenchyma.

CCR7+ CD4 T Cell Immunosurveillance Disrupted in Chronic SIV-Induced Neuroinflammation in Rhesus Brain.

CD4 T cells survey and maintain immune homeostasis in the brain, yet their differentiation states and functional capabilities remain unclear. Our approach, combining single-cell transcriptomic analysis, ATAC-seq, spatial transcriptomics, and flow cytometry, revealed a distinct subset of CCR7+ CD4 T cells resembling lymph node central memory (T CM ) cells. We observed chromatin accessibility at the CCR7, CD28, and BCL-6 loci, defining molecular features of T CM . Brain CCR7+ CD4 T cells exhibited recall proliferation and interleukin-2 production ex vivo, showcasing their functional competence. We identified the skull bone marrow as a local niche for these cells alongside other CNS border tissues. Sequestering T CM cells in lymph nodes using FTY720 led to reduced CCR7+ CD4 T cell frequencies in the cerebrospinal fluid, accompanied by increased monocyte levels and soluble markers indicating immune activation. In macaques chronically infected with SIVCL57 and experiencing viral rebound due to cessation of antiretroviral therapy, a decrease in brain CCR7+ CD4 T cells was observed, along with increased microglial activation and initiation of neurodegenerative pathways. Our findings highlight a role for CCR7+ CD4 T cells in CNS immune surveillance and their decline during chronic SIV-induced neuroinflammation highlights their responsiveness to neuroinflammatory processes. In Brief: Utilizing single-cell and spatial transcriptomics on adult rhesus brain, we uncover a unique CCR7+ CD4 T cell subset resembling central memory T cells (T CM ) within brain and border tissues, including skull bone marrow. Our findings show decreased frequencies of this subset during SIV- induced chronic neuroinflammation, emphasizing responsiveness of CCR7+ CD4 T cells to CNS disruptions. Highlights: CCR7+ CD4 T cells survey border and parenchymal CNS compartments during homeostasis; reduced presence of CCR7+ CD4 T cells in cerebrospinal fluid leads to immune activation, implying a role in neuroimmune homeostasis. CNS CCR7+ CD4 T cells exhibit phenotypic and functional features of central memory T cells (T CM ) including production of interleukin 2 and the capacity for rapid recall proliferation. Furthermore, CCR7+ CD4 T cells reside in the skull bone marrow. CCR7+ CD4 T cells are markedly decreased within the brain parenchyma during chronic viral neuroinflammation.

Epicardial fat in patients with metabolic syndrome: A systematic review and meta-analysis.

PURPOSE: Abnormally increased epicardial fat appears to be associated with an additional risk of major adverse cardiovascular events (MACEs) in the context of metabolic syndrome (MetS). However, evidence on the relationship between epicardial fat volumes (EFVs), epicardial fat thickness (EFT) and MetS remains inconsistent. METHODS: Specific searches of electronic databases from 1 January 2000 to 31 October 2022 were independently performed by two researchers. In this study, two quantification measures of epicardial fat were included: comparison of total computed tomography-based EFVs and EFT between two groups (individuals with and without MetS), estimating standardized mean difference (SMD) with corresponding 95 % confidence intervals (CIs) through a random-effects model analysis. The heterogeneity in the included studies was explored by meta-regression and subgroup analyses. RESULTS: The EFVs were significantly increased in MetS subjects compared with non-MetS subjects (SMD: 1.07, 95 % CI: 0.69-1.45, p < 0.001), and the EFT was also significantly larger in MetS patients than in the Non-MetS (SMD: 1.12, 95 % CI: 0.84-1.41, p < 0.001). We compared the Caucasian and American subgroups with the Asian and African subgroups, and the EFT was greater in the former subgroups (SMD: 1.32, 95 % CI: 0.44-2.20, p < 0.001). When comparing the EFT among the age subgroups, there was a significant SMD between adolescents and adults or elderly individuals (SMD: 1.21, 95 % CI: 0.84-1.52, p < 0.001). CONCLUSIONS: MetS patients tend to present greater EFT near the right ventricular free wall and greater total EFVs. Increased epicardial fat, an imaging biomarker, independently affects the onset of MetS.

Zilucoplan, a macrocyclic peptide inhibitor of human complement component 5, uses a dual mode of action to prevent terminal complement pathway activation.

Introduction: The complement system is a key component of the innate immune system, and its aberrant activation underlies the pathophysiology of various diseases. Zilucoplan is a macrocyclic peptide that binds and inhibits the cleavage/activation of human complement component 5 (C5). We present in vitro and ex vivo data on the mechanism of action of zilucoplan for the inhibition of C5 activation, including two clinically relevant C5 polymorphisms at R885. Methods: The interaction of zilucoplan with C5, including for clinical C5 R885 variants, was investigated using surface plasmon resonance (SPR), hemolysis assays, and ELISA. The interference of C5b6 formation by zilucoplan was investigated by native gel analysis and hemolysis assay. The permeability of zilucoplan in a reconstituted basement membrane was assessed by the partition of zilucoplan on Matrigel-coated transwell chambers. Results: Zilucoplan specifically bound human complement C5 with high affinity, competitively inhibited the binding of C5 to C3b, and blocked C5 cleavage by C5 convertases and the assembly of the cytolytic membrane attack complex (MAC, or C5b9). Zilucoplan fully prevented the in vitro activation of C5 clinical variants at R885 that have been previously reported to respond poorly to eculizumab treatment. Zilucoplan was further demonstrated to interfere with the formation of C5b6 and inhibit red blood cell (RBC) hemolysis induced by plasmin-mediated non-canonical C5 activation. Zilucoplan demonstrated greater permeability than a monoclonal C5 antibody in a reconstituted basement membrane model, providing a rationale for the rapid onset of action of zilucoplan observed in clinical studies. Conclusion: Our findings demonstrate that zilucoplan uses a dual mode of action to potently inhibit the activation of C5 and terminal complement pathway including wild-type and clinical R885 variants that do not respond to eculizumab treatment. These data may be relevant to the clinically demonstrated benefits of zilucoplan.

Meta-analysis reveals variations in microbial communities from diverse stony coral taxa at different geographical distances.

Coral-associated microbial communities play a vital role in underpinning the health and resilience of reef ecosystems. Previous studies have demonstrated that the microbial communities of corals are affected by multiple factors, mainly focusing on host species and geolocation. However, up-to-date, insight into how the coral microbiota is structured by vast geographic distance with rich taxa is deficient. In the present study, the coral microbiota in six stony coral species collected from the coastal area of three countries, including United States of America (USA), Australia and Fiji, was used for analysis. It was found that the geographic influence on the coral microbiota was stronger than the coral host influence, even though both were significant. Interestingly, the contribution of the deterministic process to bacterial community composition increased as geographical distance grew. A total of 65 differentially abundant features of functions in coral microbial communities were identified to be associated with three geolocations. While in the same coastal area of USA, the similar relationship of coral microbiota was consistent with the phylogenetic relationship of coral hosts. In contrast to the phylum Proteobacteria, which was most abundant in other coral species in USA, Cyanobacteria was the most abundant phylum in Orbicella faveolata. The above findings may help to better understand the multiple natural driving forces shaping the coral microbial community to contribute to defining the healthy baseline of the coral microbiome.

Alpiniamides E-G from the Saline Lake-Derived Streptomyces sp. QHA48 and Their Lipid Accumulation Inhibitory Activity.

Alpiniamides E-G, three previously unreported linear polyketide derivatives, along with two known compounds, were isolated from Streptomyces sp. QHA48, which was isolated from the saline lakes of Qinghai-Tibet Plateau. The structures of these compounds were determined through analysis of their spectroscopic data, as well as density functional theory prediction of NMR chemical shifts, application of the DP4+ algorithm and electronic circular dichroism (ECD) calculations. In a cell-based lipid-lowering assay, all five alpiniamides exhibited significant inhibition of lipid accumulation in HepG2 cells without inducing cytotoxic effects at a concentration of 27 µM.

Use of metagenomic next-generation sequencing in diagnosing lung abscesses caused by oral bacteria.

Lung abscesses are one of the most common lower respiratory tract infections worldwide and can seriously endanger life. However, pathogens associated with lung abscesses still cannot be detected quickly and accurately with the current microbial detection technology. Here, the case of a 53-year-old male with a lung abscess caused by oral bacteria is reported. After metagenomic next-generation sequencing was applied to identify the pathogenic microorganism, the patient recovered with precision medicine. Metagenomic next-generation sequencing is an important tool for the clinical diagnosis of infectious diseases caused by microorganisms and in guiding precision medicine.

New strategy for reinforcing polylactic acid composites: Towards the insight into the effect of biochar microspheres.

Having even particle size and regular morphology of biochar microspheres (BM) provides the possibility for preparing polylactic acid (PLA) films. Hence, the novelty is proposing a strategy for reinforcing PLA by BM. It was found that BM exhibited regular morphology, higher thermal stability, even particle size, and better pore characteristics. Although adding BM decreased the toughness of PLA due to the poor compatibility between BM and PLA, the nucleation effect of BM facilitated the crystallization in the PLA system. The tensile strength and modulus of BM/PLA composite films increased first and then decreased with increasing BM content. The stress concentration formed by BM particle agglomeration was responsible for the tensile strength and modulus decreases of BM/PLA composite films under higher BM addition. 2% BM added and 3% added composite films exhibited the best tensile strength and modulus with 64.99 MPa and 1.59 GPa, which was mainly attributed to the proper proportion of BM to PLA and the uniform distribution of BM in PLA. The results of this study confirmed the positive reinforcing effect of BM in PLA and are expected to be available in the composite film field.

Carbon emission efficiency evaluation of wastewater treatment plants: evidence from China.

A scientific evaluation of the carbon emission efficiency is crucial for ensuring the sustainable development of wastewater treatment plants (WWTPs). In this paper, we applied a non-radial data envelopment analysis (DEA) model to calculate the carbon emission efficiency of 225 WWTPs located in China. The results showed that the average carbon emission efficiency of China's WWTPs was 0.59, indicating that the efficiencies of most samples still require improvement. The carbon emission efficiency of WWTPs from 2015 to 2017 decreased because of the decrease in technology efficiency. Among the influencing factors, different treating scales had positive impact on carbon emission efficiency improvement. WWTPs with anaerobic oxic process and the first-class A standard were likely to have higher carbon emission efficiency in the 225 WWTPs. By incorporating direct and indirect carbon emissions into WWTP efficiency evaluation, this study helped decision-makers and related water authorities to better understand the contribution of WWTPs to the aquatic and atmospheric environments.

Comprehensive molecular and morphological analysis of Brachystemmacalycinum and Stellariaovatifolia in the tribe Alsineae (Caryophyllaceae).

Over the course of the recent decade, the composition of Alsineae has been drastically changed by means of molecular phylogeny. However, the genus Brachystemma has not been sampled in any of the previous studies, and its phylogenetic position is still pending. In addition, the related species Stellariaovatifolia, which has at times been placed in Brachystemma, Schizotechium, or Stellaria, has also not been sampled. Here, nuclear ribosomal internal transcribed spacer (ITS) and four plastid regions (trnL-F, matK, rbcL, rps16) were used to conduct phylogenetic analyses within Caryophyllaceae and the tribe Alsineae. Ancestral characters (petal margin and number of seeds) were reconstructed in the tribe Alsineae based on the phylogenetic results. Our results indicate that Brachystemma is nested in the tribe Alsineae and forms a monophylum with S.ovatifolia, and apically lobed petals and numerous seeds may be the ancestral characters in the tribe Alsineae. Based on our study, Stellariaovatifolia should be considered within Brachystemma, and Brachystemma is clearly a separate genus and now includes two species.