Barriers and facilitators to uptake and use of oral pre-exposure prophylaxis in pregnant and postpartum women: a qualitative meta-synthesis.

BACKGROUND: Acute HIV infection during pregnancy and in the postpartum period increases the risk of vertical transmission. The World Health Organization (WHO) has recommended preexposure prophylaxis for pregnant and postpartum women at risk of acquiring HIV. However, there are significant gaps between the actual practice and the ideal goal of preexposure prophylaxis implementation among pregnant and postpartum women. Therefore, it is important to determine what influences women's implementation of preexposure prophylaxis during pregnancy and in the postpartum period. This review aims to aggregate barriers and facilitators to preexposure prophylaxis implementation among pregnant and postpartum women. METHODS: A range of electronic databases, including PubMed, CINAHL Plus with Full Text, Embase, and Web of Science, were searched for potentially relevant qualitative studies. The search period extended from the establishment of the databases to March 16, 2023. This review used the ENTREQ (Enhancing transparency in reporting of qualitative research synthesis) statement to guide the design and reporting of qualitative synthesis. The methodological quality of the included studies was assessed using the Joanna Briggs Institute Critical Appraisal Checklist. The JBI meta-aggregation method was applied for guiding the data extraction, and the JBI ConQual method was applied for guiding the evaluation of the level of evidence for the synthesis. RESULTS: Of retrieved 2042 studies, 12 met the inclusion criteria. The total population sample included 447 participants, including 231 pregnant and postpartum women, 21 male partners, 75 healthcare providers (HCPs)/healthcare workers (HCWs), 18 policymakers, 37 mothers, and 65 women of childbearing age. A total of 149 findings with credibility ratings of "unequivocal" or "equivocal" were included in this meta-synthesis. Barriers and facilitators to preexposure prophylaxis implementation were coded into seven categories, including three facilitator categories: perceived benefits, maintaining relationships with partners, and external support, and four barriers: medication-related barriers, stigma, barriers at the level of providers and facilities, and biases in risk perception. CONCLUSION: This systematic review and meta-synthesis aggregated the barriers and facilitators of preexposure prophylaxis implementation among pregnant and postpartum women. We aggregated several barriers to maternal preexposure prophylaxis implementation, including medication-related factors, stigma, barriers at the level of providers and facilities, and risk perception biases. Therefore, intervention measures for improving preexposure prophylaxis services can be developed based on these points. PROSPERO NUMBER: CRD42023412631.

HIV rebound in HIV controllers is associated with a specific fecal microbiome profile.

HIV infection is associated with gut dysbiosis, and microbiome variability may affect HIV control when antiretroviral therapy (ART) is stopped. The TLR7 agonist, vesatolimod, was previously associated with a modest delay in viral rebound following analytical treatment interruption in HIV controllers (HCs). Using a retrospective analysis of fecal samples from HCs treated with vesatolimod or placebo (NCT03060447), people with chronic HIV (CH; NCT02858401) or without HIV (PWOH), we examined fecal microbiome profile in HCs before/after treatment, and in CH and PWOH. Microbiome diversity and abundance were compared between groups to investigate the association between specific phyla/species, immune biomarkers, and viral outcomes during treatment interruption. Although there were no significant differences in gut microbiome diversity between people with and without HIV, HCs, and CH shared common features that distinguished them from PWOH. there was a trend toward greater microbiome diversity among HCs. Treatment with vesatolimod reduced dysbiosis in HCs. Firmicutes positively correlated with T-cell activation, while Bacteroidetes and Euryarchaeota inversely correlated with TLR7-mediated immune activation. Specific types of fecal microbiome abundance (e.g. Alistipes putredinis) positively correlated with HIV rebound. In conclusion, variability in the composition of the fecal microbiome is associated with markers of immune activation following vesatolimod treatment and ART interruption.

Discovery of Highly Potent Solute Carrier 13 Member 5 (SLC13A5) Inhibitors for the Treatment of Hyperlipidemia.

In the face of escalating metabolic disease prevalence, largely driven by modern lifestyle factors, this study addresses the critical need for novel therapeutic approaches. We have identified the sodium-coupled citrate transporter (NaCT or SLC13A5) as a target for intervention. Utilizing rational drug design, we developed a new class of SLC13A5 inhibitors, anchored by the hydroxysuccinic acid scaffold, refining the structure of PF-06649298. Among these, LBA-3 emerged as a standout compound, exhibiting remarkable potency with an IC50 value of 67 nM, significantly improving upon PF-06649298. In vitro assays demonstrated LBA-3's efficacy in reducing triglyceride levels in OPA-induced HepG2 cells. Moreover, LBA-3 displayed superior pharmacokinetic properties and effectively lowered triglyceride and total cholesterol levels in diverse mouse models (PCN-stimulated and starvation-induced), without detectable toxicity. These findings not only spotlight LBA-3 as a promising candidate for hyperlipidemia treatment but also exemplify the potential of targeted molecular design in advancing metabolic disorder therapeutics.

Scleroglucan protects the intestine from irradiation-induced injury by targeting the IL-17 signaling pathway.

BACKGROUND: Intestinal tissue is extremely sensitive to ionizing radiation (IR), which is easy to cause intestinal radiation sickness, and the mortality rate is very high after exposure. Recent studies have found that intestinal immune cells and intestinal stem cells (ISCs) may play a key role in IR-induced intestinal injury. METHODS: C57BL6 mice matched for age, sex and weight were randomly grouped and intraperitoneal injected with PBS, Scleroglucan (125.0 mg/kg) or Anti-mouse IL-17A -InVivo (10 mg/kg), the number of mice in each group was n ≥ 3.Survival time, body weight, pathology, organoids and immune cell markers of the mice after IR (10.0 Gy) were compared, and the mechanism of action in intestinal tissues was verified by transcriptome sequencing. RESULTS: Scleroglucan has significant radiation protective effects on the intestine, including improving the survival rate of irradiated mice, inhibiting the radiation damage of intestinal tissue, and promoting the proliferation and differentiation of intestinal stem cells (ISCs). The results of RNA sequencing suggested that Scleroglucan could significantly activate the immune system and up-regulate the IL-17 and NF-κB signaling pathways. Flow cytometry showed that Scleroglucan could significantly up-regulate the number of Th17 cells and the level of IL-17A in the gut. IL-17A provides radiation protection. After intraperitoneal injection of Scleroglucan and Anti-mouse IL-17A -InVivo, mice can significantly reverse the radiation protection effect of Scleroglucan, down-regulate the molecular markers of intestinal stem cells and the associated markers of DC, Th1 and Th17 cells, and up-regulate the associated markers of Treg and Macrophage cells. CONCLUSION: Scleroglucan may promote the proliferation and regeneration of ISCs by regulating the activation of intestinal immune function mediated by IL-17 signaling pathway and play a protective role in IR-induced injury.

Stigma and loneliness among young and middle-aged stroke survivors: A moderated mediation model of interpersonal sensitivity and resilience.

WHAT IS KNOWN ABOUT THE SUBJECT?: Loneliness is common among young and middle-aged stroke survivors. It not only hinders the recovery of their neurological and physical functions but also increases the risk of stroke recurrence, disability, and even death. Improving the mental health of young and middle-aged stroke survivors is of utmost importance. However, previous research has not yet investigated the impact of interpersonal sensitivity and resilience on the relationship between stigma and feelings of loneliness. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: This study confirms that stigma has a positive impact on loneliness among young and middle-aged stroke survivors. Interpersonal sensitivity partially mediates the relationship between stigma and loneliness, and resilience plays a moderating role in the mediating mechanism. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Mental health nurses can formulate nursing interventions to reduce loneliness of young and middle-aged stroke survivors with the goals of improving stigma, reducing interpersonal sensitivity and cultivating resilience. ABSTRACT: Introduction Previous studies have not explored the impact of interpersonal sensitivity and resilience on the relationship between stigma and loneliness. However, improving the resilience of young and middle-aged stroke survivors and increasing their social participation is of great significance for reducing patients' loneliness of patients and promoting their physical and mental rehabilitation. Aims To investigate the influence of stigma, interpersonal sensitivity and resilience on loneliness among young and middle-aged stroke survivors. Methods A cross-sectional design was used to collect data. A total of 330 participants completed measures of stigma, resilience, interpersonal sensitivity and loneliness. The descriptive statistical approach, Pearson's correlation analysis and Hayes' PROCESS Macro Model 4 and 7 in regression analysis were used to analyse the available data. Results The results revealed that young and middle-aged stroke survivors' stigma, resilience, interpersonal sensitivity and loneliness were significantly correlated between every two variables, with coefficients ranging between -0.157 and 0.682. Interpersonal sensitivity played a partial mediating role in stigma and loneliness, accounting for 63.27% of the total effect; This process was moderated by resilience. Discussion Stigma positively predicts participants' loneliness. As a mediating mechanism with moderating, interpersonal sensitivity and resilience further explain how stigma affects loneliness. Implications for Practice Understanding this mechanism is of guiding significance to reduce loneliness of young and middle-aged stroke patients and promote their physical and mental rehabilitation.

Recent advances of engineered oncolytic viruses-based combination therapy for liver cancer.

Liver cancer is a major malignant tumor, which seriously threatens human health and increases the economic burden on patients. At present, gene therapy has been comprehensively studied as an excellent therapeutic measure in liver cancer treatment. Oncolytic virus (OV) is a kind of virus that can specifically infect and kill tumor cells. After being modified by genetic engineering, the specificity of OV infection to tumor cells is increased, and its influence on normal cells is reduced. To date, OV has shown its effectiveness and safety in experimental and clinical studies on a variety of tumors. Thus, this review primarily introduces the current status of different genetically engineered OVs used in gene therapy for liver cancer, focuses on the application of OVs and different target genes for current liver cancer therapy, and identifies the problems encountered in OVs-based combination therapy and the corresponding solutions, which will provide new insights into the treatment of liver cancer.

Crystal structure and biochemical activity of the macrodomain from rubella virus p150.

Rubella virus encodes a nonstructural polyprotein with RNA polymerase, methyltransferase, and papain-like cysteine protease activities, along with a putative macrodomain of unknown function. Macrodomains bind ADP-ribose adducts, a post-translational modification that plays a key role in host-virus conflicts. Some macrodomains can also remove the mono-ADP-ribose adduct or degrade poly-ADP-ribose chains. Here, we report high-resolution crystal structures of the macrodomain from rubella virus nonstructural protein p150, with and without ADP-ribose binding. The overall fold is most similar to macroD-type macrodomains from various nonviral species. The specific composition and structure of the residues that coordinate ADP-ribose in the rubella virus macrodomain are most similar to those of macrodomains from alphaviruses. Isothermal calorimetry shows that the rubella virus macrodomain binds ADP-ribose in solution. Enzyme assays show that the rubella virus macrodomain can hydrolyze both mono- and poly-ADP-ribose adducts. Site-directed mutagenesis identifies Asn39 and Cys49 required for mono-ADP-ribosylhydrolase (de-MARylation) activity.IMPORTANCERubella virus remains a global health threat. Rubella infections during pregnancy can cause serious congenital pathology, for which no antiviral treatments are available. Our work demonstrates that, like alpha- and coronaviruses, rubiviruses encode a mono-ADP-ribosylhydrolase with a structurally conserved macrodomain fold to counteract MARylation by poly (ADP-ribose) polymerases (PARPs) in the host innate immune response. Our structural data will guide future efforts to develop novel antiviral therapeutics against rubella or infections with related viruses.

Optical single-channel cryptosystem based on the non-negative matrix factorization and face biometric in cyan-magenta-yellow-black color space.

In this paper, an optical color single-channel asymmetric cryptosystem based on the non-negative matrix factorization (NMF) and a face biometric in cyan-magenta-yellow-black (CMYK) space is proposed. To the best of our knowledge, this is the first time that NMF has been introduced into optical color image encryption. In the proposed cryptosystem, the color image in CMYK space is first decomposed into four color channels: C, M, Y, and K. By performing NMF operations on the four color channels, the four basic and sparse matrices can be obtained, respectively, which achieves asymmetry and saves computational resources. The four basis matrices can be used as private keys, and the four coefficient matrices are synthesized by the inverse discrete wavelet transform for subsequent encryption. Finally, the synthesized image is encoded with double random phase encoding based on phase truncation (PT). Compared with the existing PT-based cryptosystems, our cryptosystem can improve security against a special attack. In addition, the chaotic random phase mask is generated by a face biometric, which is noncontact and unique. Numerical simulation results are shown to verify the feasibility and robustness of our cryptosystem. Further, the proposed cryptosystem can be extended to encrypt multiple images conveniently.

Multiple Roles of the Low-Affinity Calcium Uptake System in Drechslerella dactyloides, a Nematode-Trapping Fungus That Forms Constricting Rings.

(1) Background: the low-affinity calcium uptake system (LACS) has been shown to play a crucial role in the conidiation and formation of adhesive nets and knobs by nematode-trapping fungi (NTF), but its involvement in the formation of constricting rings (CRs), mechanical traps to capture free-living nematodes, remains unexplored. (2) Methods: we investigated the function of two LACS genes (DdaFIG_1 and DdaFIG_2) in Drechslerella dactyloides, an NTF that forms CRs. We generated single (DdaFIG_1Ri and DdaFIG_2Ri) and double (DdaFIG_1,2Ri) knockdown mutants via the use of RNA interference (RNAi). (3) Results: suppression of these genes significantly affected conidiation, trap formation, vegetative growth, and response to diverse abiotic stresses. The number of CRs formed by DdaFIG_1Ri, DdaFIG_2Ri, and DdaFIG_1,2Ri decreased to 58.5%, 59.1%, and 38.9% of the wild-type (WT) level, respectively. The ring cell inflation rate also decreased to 73.6%, 60.6%, and 48.8% of the WT level, respectively. (4) Conclusions: the LACS plays multiple critical roles in diverse NTF.

The effectiveness of e-health on reducing stigma, improving social support and quality of life among people living with HIV: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Many people living with HIV reported poor quality of life, which was primarily due to HIV-related stigma and the lack of social support. Compared with face-to-face interventions, e-health interventions are reported to have potential to help people living with HIV improve their adherence to antiretroviral therapy, promote their management of HIV and depressive symptoms. However, in the literature, the effectiveness of e-health interventions in helping people living with HIV reduce stigma, improve social support and quality of life is unclear. OBJECTIVE: To examine the effectiveness of e-health interventions in reducing stigma and improving social support and quality of life among people living with HIV. DESIGN: This study is a systematic review and meta-analysis of randomized controlled trials following the Cochrane Handbook guidelines and PRISMA2020. METHODS: A comprehensive search was conducted from inception to 1st December 2022 in six databases: PubMed, CINAHL Plus with Full Text, PsycINFO (Ovid), Embase, Web of Science, and CENTRAL (Ovid), and an updated search took place on 11st June 2023. Two authors independently screened the studies and extracted the data. Cochrane's bias risk tool for randomized controlled trials was used to examine the methodological quality of the included studies. The intervention effect was estimated by calculating the standardized mean difference (SMD) and 95 % confidence interval (CI) using Review Manager 5.3. A sensitivity analysis was conducted to test the rigor of the pooled results using one-study-out method. The certainty of evidence was assessed using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. RESULTS: Nine studies met eligibility criteria and were included in this review. The results of the meta-analysis showed that e-health interventions could statistically significantly reduce stigma (SMD: -0.29, 95 % CI: [-0.48, -0.10], p = 0.002) and improve quality of life (SMD = 0.49, 95 % CI: [0.30, 0.68], P < 0.001), but had no significant effects on social support (SMD = -0.01, 95 % CI: [-0.48, 0.46] P = 0.96). CONCLUSIONS: E-health interventions could reduce stigma and improve quality of life among people living with HIV. More studies are needed to further explore if e-health interventions can improve the social support for people living with HIV and investigate how to integrate e-health interventions into the existing health models to help people living with HIV treat and manage HIV/AIDS. REGISTRATION: The protocol of this study has been registered in the database PROSPERO (registration ID: CRD42022373299).

UN-PUNet for phase unwrapping from a single uneven and noisy ESPI phase pattern.

The wrapped phase patterns of objects with varying materials exhibit uneven gray values. Phase unwrapping is a tricky problem from a single wrapped phase pattern in electronic speckle pattern interferometry (ESPI) due to the gray unevenness and noise. In this paper, we propose a convolutional neural network (CNN) model named UN-PUNet for phase unwrapping from a single wrapped phase pattern with uneven grayscale and noise. UN-PUNet leverages the benefits of a dual-branch encoder structure, a multi-scale feature fusion structure, a convolutional block attention module, and skip connections. Additionally, we have created an abundant dataset for phase unwrapping with varying degrees of unevenness, fringe density, and noise levels. We also propose a mixed loss function MS_SSIM + L2. Employing the proposed dataset and loss function, we can successfully train the UN-PUNet, ultimately realizing effective and robust phase unwrapping from a single uneven and noisy wrapped phase pattern. We evaluate the performance of our method on both simulated and experimental ESPI wrapped phase patterns, comparing it with DLPU, VUR-Net, and PU-M-Net. The unwrapping performance is assessed quantitatively and qualitatively. Furthermore, we conduct ablation experiments to evaluate the impact of different loss functions and the attention module utilized in our method. The results demonstrate that our proposed method outperforms the compared methods, eliminating the need for pre-processing, post-processing procedures, and parameter fine-tuning. Moreover, our method effectively solves the phase unwrapping problem while preserving the structure and shape, eliminating speckle noise, and addressing uneven grayscale.

The experience of healthcare workers to HIV pre-exposure prophylaxis (PrEP) implementation in low- and middle-income countries: a systematic review and qualitative meta-synthesis.

Background: The effectiveness of pre-exposure prophylaxis has been extensively documented. However, there are substantial gaps between the actual implementation of pre-exposure prophylaxis and the ideal goal, especially in low-and middle-income countries. Healthcare workers play critical roles in the pre-exposure prophylaxis implementation, and they have more multi-level experiences about the barriers of pre-exposure prophylaxis implementation and how to facilitate it. However, the evidence aiming to synthesize their experiences is limited. Objective: This study aims to aggregate the healthcare workers' experiences of providing pre-exposure prophylaxis in low-and middle-income countries, and find the barriers, facilitators, and recommendations of pre-exposure prophylaxis implementation. Methods: The ENTREQ (Enhancing transparency in reporting the synthesis of qualitative research) statement was used to guide the design and reporting of this qualitative meta-synthesis. A comprehensive search was conducted from inception of databases to 16th March 2023 in four databases: PubMed, CINAHL Plus with Full Text, Embase, Web of Science. The quality appraisal was conducted using the Joanna Briggs Institute Critical Appraisal Checklist. JBI's meta-aggregation approach was used to guide the data extraction and synthesis, and the JBI ConQual approach was used to evaluate the evidence level of the synthesized findings. Results: Fourteen articles with good methodological quality were included in this review. A total of 122 findings were extracted and 117 findings with credibility ratings of "unequivocal" or "equivocal" were included in this meta-synthesis. The eligible findings were aggregated into 13 new categories and subsequently developed into 3 synthesized findings: the barriers, facilitators, and recommendations of pre-exposure prophylaxis implementation in low-and middle-income countries. The overall ConQual score of all three synthesized findings was rated as "low." Conclusion: This review aggregated the experience of health care workers implementing pre-exposure prophylaxis in low-and middle-income countries and we could focus on the following key points to promote the uptake of pre-exposure prophylaxis: improve knowledge about pre-exposure prophylaxis, create a supportive environment, address medication-related barriers, increase the human resources and financial investments, and diversify the providing models. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/. The protocol of this review has been registered in the International Prospective Register of Systematic Reviews (PROSPERO, CRD42023411604).

Opportunities and Challenges for Inhibitors Targeting Citrate Transport and Metabolism in Drug Discovery.

Lipid metabolism disorder is closely related to metabolic diseases, inflammation, and cancer. The concentration of citrate in the cytosol has a significant impact on lipid synthesis. The expression of citrate transporters (SLC13A5 and SLC25A1) and metabolic enzymes (ACLY) proves to be substantially raised in various diseases related to disorders of lipid metabolism, such as hyperlipemia, nonalcoholic fatty liver disease, and prostate cancer. Targeting key proteins in the citrate transport and metabolic pathways is considered an effective strategy for treating various metabolic diseases. However, there is currently only one ACLY inhibitor approved for marketing, and no SLC13A5 inhibitor has entered clinical research. Further development of drugs targeting citrate transport and metabolism is needed for the treatment of metabolic diseases. This perspective summarizes the biological role, therapeutic potential, and research progress of citrate transport and metabolism and then discusses the achievements and prospects of modulators targeting citrate transport and metabolism for therapeutic applications.

Activatable BODIPY-chromene NIR-II probes with small spectral crosstalk enable high-contrast in vivo bioimaging.

Herein, we design a novel "crossbreeding" dye (BC-OH) within the second near-infrared (NIR-II) window based on BODIPY and chromene chromophores. BC-OH can serve as a platform to construct activatable NIR-II probes with small spectral crosstalk, thereby making a breakthrough in imaging in vivo H2O2 fluctuation in an APAP-induced liver injury model with high signal-to-background ratio.

[Electroacupuncture improves ischemic myocardial injury by activating Nrf2/HO-1 signaling pathway to inhibit ferroptosis in rats].

OBJECTIVE: To explore the role of nuclear factor E2 related factor 2 (Nrf2) / heme oxygenase (HO-1) signal pathway in electroacupuncture (EA) induced improvement of acute myocardial ischemia (AMI) and its relationship with ferroptosis in rats. METHODS: Male SD rats were randomly and equally divided into sham operation, model, EA and EA+ML385 (inhibitor of Nrf2) groups (n=8). The rat model of AMI was established by ligating the descending anterior branch of the left coronary artery. EA (2 Hz/100 Hz) was applied to bilateral "Shenmen"(HT7) and "Tongli"(HT5) for 20 min, once daily for 7 days. The electrocardiogram (ECG) of standard Ⅱ (ECG ST) lead and heart rate (HR) in each group was recorded and analyzed before and after modeling and after treatment by using PowerLab physiological recorder system. Histopathological changes of myocardial tissue were observed by H.E. staining, and the ultrastructure of myocardiocytes of cardiac apical tissue was observed under transmission electron microscope. The contents of Fe2+ and glutathione (GSH) in the myocardial tissue were measured by chromato-metry. The protein expression levels of Nrf2, HO-1, glutathione peroxidase 4 (GPX4), ferritin heavy chain polypeptide 1 (FTH1) and long chain acyl CoA synthase 4 (ACSL4) in the myocardial tissue were detected by Western blot. RESULTS: Compared with the sham operation group, the HR, ECG ST, Fe2+ content, expression levels of Nrf2, HO-1, FTH1 and ACSL4 proteins in myocardial tissues were significantly increased (P<0.01), while GSH content and GPX4 protein expression considerably decreased (P<0.01) in the model group. Compared with the model group, both EA and EA+ML385 groups had an obvious decrease in HR, Fe2+ content, and ACSL4 levels (P<0.01), and an increase in the expression levels of GPX4 and FTH1 proteins (P<0.01), EA (rather than EA+ML385) effectively down-regulated ECG ST, and up-regulated GSH, Nrf2 and HO-1 (P<0.01), whereas EA+ML385 apparently down-regulated expression levels of Nrf2 and HO-1 (P<0.01). It shows that ML385 pronouncedly weaken the effects of EA in slowing down ECG ST and HR, down-regulating Fe2+ content and ACSL4 expression (P<0.01), up-regulating GSH content, Nrf2, HO-1, GPX4 and FTH1 expressions (P<0.01). H.E. staining showed disordered arrangement and hyperplasia of myocardiocytes, enlarged myocardial fiber gap, agglomerated and deeply stained myoplasma, and some broken myocardial fibers with irregular mass and local tissue fibrosis in the model group, which was relatively milder in both EA and EA+ML385 groups. Compared with the sham operation group, the model group showed decreased mitochondrial atrophy, increased membrane density, and disappearance or reduction of cristae in myocardial cells，which was improved in the EA group. CONCLUSION: EA of HT7 and HT5 has a protective effect on ischemic myocardium in rats, which may be related to its effects in reducing oxidative stress by regulating Nrf2/HO-1 signaling pathway, and inhibiting "iron death" of myocardial cells.

Ischemic Stroke and Dysbiosis of Gut Microbiota: Changes to LPS Levels and Effects on Functional Outcomes.

Context: The intestinal microbiota and their metabolites play an important role in acute ischemic stroke (AIS) and modulate brain functions directly or indirectly through immune, endocrine, vagal, and other humoral pathways. However, relatively few investigations have evaluated the gut microbiome and its levels of inflammatory factors or the potential associations of those factors with stroke outcomes in patients who have had acute ischemic stroke (AIS), with different stroke severities. Objective: The study intended to determine if AIS patients would have different gut microbiota and inflammatory-factor levels than healthy individuals and if those levels would be associated with the stroke's severity and the patient's prognosis. Design: The research team performed a prospective observational study. Setting: The study took place in the Department of Rehabilitation at the General Hospital of Wanbei Coal and Electricity Group, which is the Third Affiliated Hospital of Bengbu Medical College in Suzhou, Anhui, China. Participants: Participants were 90 patients who had received a diagnosis and treatment of AIS within 48 hours of the stroke's onset at the hospital, between October 2021 and March 2022. Groups: The research team performed multiple comparisons of the baseline demographic and clinical characteristics, the gut microbiota, and levels of inflammatory factors of a number of groups: (1) the AIS patients, the AIS group, to the healthy controls, the control group; (2) the AIS participants who had had a mild or moderate stroke, the mild-moderate group, and those who had had a severe stroke, the severe group; (3) the AIS participants who had had a good primary outcome, the good outcome group, and those who had had a poor primary outcome, the poor outcome group; (4) the mild-moderate and severe groups to the control group; and (5) the good outcome and poor outcome groups to the control group. Outcome Measures: The research team: (1) obtained participants' fecal samples within 72 hours of admission; (2) collected baseline data for the included AIS patients and controls; (3) used 16S rRNA gene sequencing and an enzyme-linked immunosorbent assay (ELISA) to compare the fecal microbial compositions, lipopolysaccharide (LPS) contents, and inflammatory-factor levels between groups; and (4) evaluated the associations of the fecal microbial compositions with severity of stroke and 90-day functional outcomes, using logistic-regression models. Results: The gut microflora distinguished AIS patients from healthy controls. The LPS and inflammatory-factor levels were associated with an increased risk of poor functional outcomes at day 90. Conclusions: Dysbiosis of gut microbiota and LPS and inflammatory-factor levels can increase AIS patients' subsequent risks for poor functional outcomes, indicating that the dysbiosis and levels could be potential prognostic markers and therapeutic targets for stroke.

Association between the stress hyperglycemia ratio and severity of coronary artery disease under different glucose metabolic states.

BACKGROUND: Stress hyperglycemia ratio (SHR) is significantly related to adverse cardiovascular clinical outcomes and increased in-hospital mortality. However, the relationship between SHR and coronary artery disease (CAD) severity has hitherto not been reported. This study sought to clarify the relationship between the SHR and CAD severity of individuals with different glucose metabolic statuses. METHODS: A retrospective analysis was performed on 987 patients who underwent coronary angiography (CAG) from October 2020 to May 2022. Based on CAG results, patients were divided into single-vessel CAD and multi-vessel CAD groups. All subjects were stratified into three groups according to the tertiles of the SHR (T1 group: SHR < 0.930; T2 group: 0.930 ≤ SHR < 1.154; T3 group: 1.154 ≤ SHR). Moreover, according to glucose metabolism status, study subjects were divided into normal glucose regulation (NGR), pre-diabetes mellitus (pre-DM) and diabetes mellitus (DM) groups. Finally, the correlation between SHR and CAD severity was analyzed by logistic regression analysis and receiver operating characteristic (ROC) curve. RESULTS: The results showed significantly higher SHR in the multi-vessel CAD group than in the single-vessel group. Logistic regression analysis showed that SHR was an independent risk factor for multi-vessel CAD when used as a continuous variable (OR, 4.047; 95% CI 2.137-7.663; P < 0.001). After adjusting for risk factors, the risk of multi-vessel CAD in the T2 and T3 groups was 1.939-fold (95% CI 1.341-2.804; P < 0.001) and 1.860-fold (95% CI 1.272-2.719; P = 0.001) higher than in the T1 group, respectively. The area under the curve (AUC) of ROC plots was 0.613 for SHR. In addition, SHR was significantly correlated with an increased risk of multi-vessel CAD in the pre-DM and DM groups. CONCLUSIONS: Our study indicated that SHR was significantly correlated with the risk of multi-vessel CAD and predicted CAD severity, especially in pre-DM and DM patients.

Optical double-image cryptosystem based on generalized singular value decomposition and five-dimensional hyperchaotic maps.

In this paper, we propose an asymmetric optical double-image cryptosystem based on generalized singular value decomposition (GSVD) and five-dimensional (5D) hyperchaotic maps. In the proposed cryptosystem, the two plain images are first decomposed into five components by the GSVD operation. The two unitary matrices obtained by GSVD are encoded as a complex function, which is then modulated by the chaotic random phase masks (CRPMs). The private key and the final encryption result are generated by phase-truncation and amplitude-truncation operations. The GSVD operation can decompose two images at the same time and is used to generate the private key that enables the encryption process to be asymmetric. Compared with the existing phase-truncated-based cryptosystems, our cryptosystem can improve security against a special attack. In addition, the CRPMs are generated by 5D hyperchaotic maps, which have a larger parameter space and better randomness. Numerical simulation results are shown to verify the feasibility and robustness of our cryptosystem. Furthermore, the proposed cryptosystem can be extended to encrypt multiple images conveniently.

[Changes in physicochemical property and microbial community of Pseudostellaria heterophylla soil at diffe-rent fallow ages]. / 太子参不同休耕年限土壤理化特征和微生物群落变化.

Pseudostellaria heterophylla is authentic traditional Chinese herbal medicine in Fujian Province. P. hete-rophylla suffers from serious consecutive monoculture problems. Fallow can alleviate such problems, but the mecha-nism is still unclear. In this study, high-throughput sequencing was performed to analyze the changes in soil microbial community structure and diversity in the P. heterophylla soil at different fallow ages as well as their relationships with soil physicochemical properties and phenolic acids. The results showed that fungal community diversity decreased but bacterial community diversity increased in fallow soils compared with the control soil of P. heterophy-lla. For bacterial communities, the relative abundance of Acidobacteria increased, while that of Proteobacteria and Actinobacteria decreased in fallow soils. For fungal communities, the relative abundance of dominant phyla had no significant difference between fallow and control soils. Soil acidity and organic matter content showed a trend of weakening and decreasing, respectively, with the increases of fallow years. In addition, with the increases of fallow years, the content of phenolic acids in soil, including benzoic acid and salicylic acid, showed significant decrease, while some other phenolic acids such as p-coumaric acid were accumulated obviously. Taken together, fallow could efficiently ameliorate the structure of soil microbial community and soil properties of P. heterophylla, and thus alleviate the effects of continuous cropping.

A critical update on the strategies towards small molecule inhibitors targeting Serine/arginine-rich (SR) proteins and Serine/arginine-rich proteins related kinases in alternative splicing.

>90% of genes in the human body undergo alternative splicing (AS) after transcription, which enriches protein species and regulates protein levels. However, there is growing evidence that various genetic isoforms resulting from dysregulated alternative splicing are prevalent in various types of cancers. Dysregulated alternative splicing leads to cancer generation and maintenance of cancer properties such as proliferation differentiation, apoptosis inhibition, invasion metastasis, and angiogenesis. Serine/arginine-rich proteins and SR protein-associated kinases mediate splice site recognition and splice complex assembly during variable splicing. Based on the impact of dysregulated alternative splicing on disease onset and progression, the search for small molecule inhibitors targeting alternative splicing is imminent. In this review, we discuss the structure and specific biological functions of SR proteins and describe the regulation of SR protein function by SR protein related kinases meticulously, which are closely related to the occurrence and development of various types of cancers. On this basis, we summarize the reported small molecule inhibitors targeting SR proteins and SR protein related kinases from the perspective of medicinal chemistry. We mainly categorize small molecule inhibitors from four aspects, including targeting SR proteins, targeting Serine/arginine-rich protein-specific kinases (SRPKs), targeting Cdc2-like kinases (CLKs) and targeting dual-specificity tyrosine-regulated kinases (DYRKs), in terms of structure, inhibition target, specific mechanism of action, biological activity, and applicable diseases. With this review, we are expected to provide a timely summary of recent advances in alternative splicing regulated by kinases and a preliminary introduction to relevant small molecule inhibitors.