Venous thrombolysis prior to mechanical thrombectomy reduces glycocalyx damage in patients with acute ischemic stroke.

Introduction: The administration of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) in the treatment of acute ischemic stroke (AIS) has been a subject of debate, and its potential benefits remain uncertain. This retrospective study aimed to investigate the effect of preoperative IVT on glycocalyx damage in patients with cerebral ischemia-reperfusion injury (IRI). Methods: A cohort of 106 patients with acute large vessel occlusion in the anterior circulation treated with mechanical thrombectomy was enrolled. The levels of the glycocalyx damage marker, syndecan-1, were measured in the peripheral blood of these patients to assess glycocalyx damage during IRI, and clinical outcomes were compared between patients receiving MT alone vs. combined IVT and MT. Results: The study results indicate that thrombolytic drugs have a significant impact on syndecan-1 levels in the blood. Compared to patients who underwent direct MT, those who received preoperative IVT had significantly lower levels of syndecan-1 in their blood. Although preoperative IVT did not alter the final clinical outcomes, the levels of syndecan-1 shedding reflect the extent of damage to the endothelial glycocalyx. Discussion: This suggests that using thrombolytic drugs before mechanical thrombectomy may reduce endothelial glycocalyx damage in patients with ischemia-reperfusion injury. These findings provide indirect clinical evidence supporting the preoperative use of intravenous thrombolysis in such patients.

Comparative long-term outcomes of unicompartmental and total knee arthroplasty in knee osteoarthritis patients: a systematic review and meta-analysis.

Background: Long-term outcomes for knee osteoarthritis patients undergoing unicompartmental knee arthroplasty (UKA) and total knee arthroplasty (TKA) remain inconclusive. Objectives: This study aims to evaluate the long-term outcomes over five years, including Knee Society Pain Scores (KSPS), Knee Society Scores (KSS), Knee Society Function Scores (KSFS), range of motion (ROM), and survival rates-of UKA vs. TKA in knee osteoarthritis patients. Design: Systematic review using data from randomized controlled and cohort trials, and world databases. Data sources: Researchers searched Medline, Embase, Cochrane Controlled Register of Trials, and ClinicalTrials.gov from January 1990 to March 2024. Eligibility criteria for selecting studies: The researchers selected studies based on adult participants with knee osteoarthritis. Eligible studies compare UKA and TKA reports on clinical or surgical outcomes, including KSPS, KSS, KSFS, ROM and survival rates, over 5 years. The researchers excluded the studies fewer than five years, or if English text was unavailable. Results: Researchers categorized twenty-nine eligible studies into three groups: five randomized controlled trials, 11 registries and database studies, and 13 cohort studies. The analysis revealed that neither TKA nor UKA definitively outperformed the other in terms of pain (SMD (95% CI): -0.06 [-0.41, 0.28], I 2 = 90%) and KSS scores (SMD (95% CI): -0.07 [-0.23, 0.008], I 2 = 81%) over a period of five years. However, KSFS (SMD (95% CI): -0.30 [-0.43, -0.17], I 2 = 74%) and ROM (SMD (95% CI): -0.78 [-1.11, -0.46], I 2 = 92%) tended to favor UKA, and survival rate favor TKA at 5 or over 5-year follow-up periods. Conclusions: UKA shows a trend towards better outcomes in KSFS and ROM, alongside a more favorable survival rate in TKA at the five-year and beyond follow-up periods. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=517835, PROSPERO (CRD42024517835).

The combination of a PTP1B inhibitor, TNFR2 blocker, and PD­1 antibody suppresses the progression of non­small cell lung cancer tumors by enhancing immunocompetence.

Lung cancer is increasingly recognized as a leading cause of cancer­related mortality. Immunotherapy has emerged as a promising therapeutic approach for lung cancer, particularly non­small cell lung cancer (NSCLC). Nonetheless, the response rate to programmed cell death 1 (PD­1) inhibitors remains less than optimal. It has been suggested that protein tyrosine phosphatase 1B (PTP1B) plays a crucial role in the development and progression of cancer by facilitating T cell expansion and cytotoxicity. Our previous research demonstrated that the combination of tumor necrosis factor receptor 2 (TNFR2) with immune activity treatments synergistically suppresses tumor growth. This insight led to exploring the efficacy of a combined treatment strategy involving PD­1 inhibitors, PTP1B inhibitors and TNFR2 antibodies (triple therapy) in NSCLC. In this context, the therapeutic effectiveness of these combination immunotherapies was validated in mouse models with NSCLC by analyzing the expansion and function of immune cells, thereby assessing their impact on tumor growth. The results indicated that inhibiting PTP1B decreases the expression of PD­L1 and TNFR2 on LLC cells, along with an increase in the proportion of CD4+T and CD8+T cells. Compared with other treatment groups, the triple therapy significantly reduced tumor volume in mice with NSCLC and extended their survival. Moreover, this combination therapy altered the distribution of myeloid­derived suppressor cells, dendritic cells, B cells and M1 macrophages, while increasing the proportion of CD8+T cells and reducing the proportion of Treg cells in the spleens, lymph nodes, and tumors of NSCLC models. The triple therapy also resulted in a decrease in PD­L1, PTP1B and TNFR2 expression within NSCLC tumor tissues in mice. Overall, the triple therapy effectively suppressed tumor growth and improved outcomes in mice with NSCLC by modulating immune cell distribution and reducing levels of target immune proteins.

Research on mine water source classifications based on BO-CatBoost.

Mine water surge is one of the main safety risks in coal mines. This research offers a novel mine water source identification model (BO-CatBoost) to successfully avoid and control mine sudden water catastrophes by properly identifying the sources of mine water. First, the classification model is trained and built using the Categorical Boosting (CatBoost) algorithm. The Gaussian process Bayesian optimization (BO) algorithm is used to optimize parameters, and the optimal parameter combination is integrated into the CatBoost algorithm to build the BO-CatBoost mine water source identification model, which further improves the accuracy of mine water source identification. The model was also applied to the Pingdingshan mine to verify the practicality of the model. Then, 29 groups of unknown water sources in Pingdingshan were selected as validation samples for the model and compared with the conventional CatBoost, Light Gradient Boosting Machine (LightGBM), and Extreme Gradient Boosting (Xgboost) models. The comparison results demonstrate that the accuracy of LightGBM, Xgboost, CatBoost, and BO-CatBoost models can reach 69%, 79.3%, 79.3%, and 100% respectively, and the RMSE is 0.947, 0.643, 0.719, and 0.0 respectively. The comprehensive analysis shows that, when it comes to mine water source detection, the BO-CatBoost model performs noticeably better than other models in terms of discriminative accuracy and generalization capacity. Lastly, the multi-output prediction and decision-making process of the BO-CatBoost water source identification model is visualized by the interpretability analysis performed with the SHAP approach. The research demonstrates that the BO-CatBoost model can more precisely and impartially identify mine water sources, offering fresh concepts for mine water source detection.

Mapping of oil spills in China Seas using optical satellite data and deep learning.

Oils spilled into the ocean can form various weathered oils (non-emulsified oil slicks (NEOS), oil emulsions (OE)) which threaten the oceanic and coastal environments and ecosystems. Optical remote sensing has the unique ability to discriminate oil types and quantify oil volumes as their spectral contrasts with oil-free seawater. Here, a deep learning-based model is developed for identification, classification, and quantification of various oil types. Based on the oil-contained datasets collected from 7 satellite sensors from April 2019 to August 2023, the origin, quantity, and spatial distribution of oils spilled from ships and rigs in the China Seas are mapped in detail. We found that oil spill incidents are primarily from ship discharges (85.8 %), while platform leaks lead to more oil emulsions (58.6 % compared to 13.1 % from ships), which illuminates that the drilling oils are the main source of oil spill pollution in China Seas. The spilled oils correlate with major port locations, including offshore Qingdao and Rongcheng, Bohai Bay, the adjacent areas of Beihai, and Hue and Danang in Vietnam. This study provides new insights into the assessment and management of offshore and marine oil spills.

Oxysterol Sensing Through GPR183 Triggers Endothelial Senescence in Hypertension.

BACKGROUND: Despite endothelial dysfunction being an initial step in the development of hypertension and associated cardiovascular/renal injuries, effective therapeutic strategies to prevent endothelial dysfunction are still lacking. GPR183 (G protein-coupled receptor 183), a recently identified G protein-coupled receptor for oxysterols and hydroxylated metabolites of cholesterol, has pleiotropic roles in lipid metabolism and immune responses. However, the role of GPR183 in the regulation of endothelial function remains unknown. METHODS: Endothelial-specific GPR183 knockout mice were generated and used to examine the role of GPR183 in endothelial senescence by establishing 2 independent hypertension models: desoxycorticosterone acetate/salt-induced and Ang II (angiotensin II)-induced hypertensive mice. Echocardiography, transmission electron microscopy, blood pressure measurement, vasorelaxation response experiments, flow cytometry analysis, and chromatin immunoprecipitation analysis were performed in this study. RESULTS: Endothelial GPR183 was significantly induced in hypertensive mice, which was further confirmed in renal biopsies from subjects with hypertensive nephropathy. Endothelial-specific deficiency of GPR183 markedly alleviated cardiovascular and renal injuries in hypertensive mice. Moreover, we found that GPR183 regulated endothelial senescence in both hypertensive mice and aged mice. Mechanistically, GPR183 disrupted circadian signaling by inhibiting PER1 (period circadian regulator 1) expression, thereby facilitating endothelial senescence and dysfunction through the cAMP (cyclic adenosine monophosphate)/PKA (protein kinase A)/CREB (cAMP-response element binding protein) signaling pathway. Importantly, pharmacological inhibition of the oxysterol-GPR183 axis by NIBR189 or clotrimazole ameliorated endothelial senescence and cardiovascular/renal injuries in hypertensive mice. CONCLUSIONS: This study discovers a previously unrecognized role of GPR183 in promoting endothelial senescence. Pharmacological targeting of GPR183 may be an innovative therapeutic strategy for hypertension and its associated complications.

Hematoporphyrin photodynamic therapy for treatment of pathological scar with ulceration: A case report.

Pathological scars result from abnormal wound healing and represent a fibrotic process in the repair of skin injuries. Post-burn scars are prone to malignant transformation, especially when ulceration occurs, raising concerns for precancerous lesions. We report a case of a 56-year-old female with a 50-year history of a large burn scar on her left forearm. The scar developed non-healing ulceration with local pain and itching over the past three years. Treatment with hematoporphyrin photodynamic therapy (HpD-PDT) led to resolution of the ulceration, thinning of the scar tissue, and significant alleviation of pain and itching. After a five-year follow-up, there has been no recurrence of ulceration, suggesting that photodynamic therapy effectively promotes wound healing in scarred tissue with ulcerations.

Social network strategies to distribute HIV self-testing kits: a global systematic review and network meta-analysis.

INTRODUCTION: Social network strategies, in which social networks are utilized to influence individuals or communities, are increasingly being used to deliver human immunodeficiency virus (HIV) interventions to key populations. We summarized and critically assessed existing research on the effectiveness of social network strategies in promoting HIV self-testing (HIVST). METHODS: Using search terms related to social network interventions and HIVST, we searched five databases for trials published between 1st January 2010 and 30th June 2023. Outcomes included uptake of HIV testing, HIV prevalence and linkage to antiretroviral therapy (ART) or HIV care. We used network meta-analysis to assess the uptake of HIV testing through social network strategies compared with control methods. A pairwise meta-analysis of studies with a comparison arm that reported outcomes was performed to assess relative risks (RR) and their corresponding 95% confidence intervals (CI). RESULTS: Among the 4496 manuscripts identified, 39 studies fulfilled the inclusion criteria, including one quasi-experimental study, 22 randomized controlled trials and 16 observational studies. Networks HIVST testing was organized by peers (distributed to known peers, 15 studies), partners (distributed to their sexual partners, 16 studies) and peer educators (distributed to unknown peers, 8 studies). Among social networks, simulating the possibilities of ranking position, peer distribution had the highest uptake of HIV testing (84% probability), followed by partner distribution (80% probability) and peer educator distribution (74% probability). Pairwise meta-analysis showed that peer distribution (RR 2.29, 95% CI 1.54-3.39, 5 studies) and partner distribution (RR 1.76, 95% CI 1.50-2.07, 10 studies) also increased the probability of detecting HIV reactivity during testing within the key population when compared to the control. DISCUSSION: All of the three social network distribution strategies enhanced the uptake of HIV testing compared to standard facility-based testing. Linkage to ART or HIV care remained comparable to facility-based testing across the three HIVST distribution strategies. CONCLUSIONS: Network-based HIVST distribution is considered effective in augmenting HIV testing rates and reaching marginalized populations compared to facility-based testing. These strategies can be integrated with the existing HIV care services, to fill the testing gap among key populations globally. PROSPERO NUMBER: CRD42022361782.

Function of miR-21-5p derived from ADSCs-exos on the neuroinflammation after cerebral ischemia.

INTRODUCTION: Cerebral ischemia (CI) induces a profound neuroinflammatory response, but the underlying molecular mechanism remains unclear. Exosomes from adipose-derived stem cells (ADSC-exos) have been found to play a crucial role in cell communication by transferring molecules including microRNAs (miRNAs), which have been shown to modulate the inflammatory response after CI and are viable molecular targets for altering brain function. The current study aimed to explore the contribution of ADSC-exosomal miR-21-5p to the neuroinflammation after CI. METHODS: The differentially expressed miR-21-5p in CI was screened based on literature search. The target mRNAs of miR-21-5p were predicted using online databases and verified by luciferase reporter assay. Then, BV2 cells were treated with hemin to simulate the inflammatory response after CI, and its animal model was induced using the MCAO method. Ischemia was evaluated in rats using 2, 3, 5-triphenyl tetrazolium chloride (TTC) staining. ADSCs-exos were further isolated and identified by western blot analysis and transmission electron microscope. RESULTS: MiR-21-5p was significantly down-regulated in CI and alleviated neuropathic damage after CI by the PIK3R1/PI3K/AKT signaling axis. And miR-21-5p derived from ADSCs-exos alleviated neuroinflammation after CI via promoting microglial M2 polarization. CONCLUSION: We demonstrated that ADSC-exosomal miR-21-5p mitigated post-CI inflammatory response through the PIK3R1/PI3K/AKT signaling axis and could offer neuroprotection after CI through promoting polarization of M2 microglia.

Construction of a gene signature associated with anoikis to evaluate the prognosis and immune infiltration in patients with colorectal cancer.

Background: Colorectal cancer (CRC) is characterized by a high metastasis rate, leading to poor prognosis and increased mortality. Anoikis, a physiological process, serves as a crucial barrier against metastasis. The objective of this research is to construct a prognostic model for CRC based on genes associated with anoikis. Methods: The study involved differential analysis and univariate Cox analysis of anoikis-related genes (ARGs), resulting in the selection of 47 genes closely associated with prognosis. Subsequently, unsupervised k-means clustering analysis was conducted on all patients to identify distinct clusters. Survival analysis, principal component analysis (PCA), and t-distributed stochastic neighbor embedding (t-SNE) analysis were performed on the different clusters to investigate associations within the clusters. Gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) were utilized to assess metabolic pathway enrichment between the identified clusters. Furthermore, single-sample GSEA (ssGSEA) was applied to explore variations in immune infiltration. Multivariable Cox regression and least absolute shrinkage and selection operator (LASSO) analyses were conducted to construct a risk model based on ten signatures, which enabled the grouping of all samples according to their risk scores. The prognostic value of the model was validated using receiver operating characteristic (ROC) curves, area under the curve (AUC) calculations, and survival curves. Additionally, the expression of candidate genes was validated using quantitative real-time polymerase chain reaction (qRT-PCR). Results: Forty-seven survival-related ARGs were screened out. Somatic mutation analysis showed that these genes revealed a high mutation rate. Based on their expression, two clusters were identified. Cluster B patients exhibited a shortened overall survival and higher immune infiltration. A risk scoring model including ten genes was subsequently developed, which exhibited excellent prognostic predictive ability for CRC, as evidenced by the survival curve, ROC curve, and AUC curve. In addition, a nomogram was developed for predicting 3- and 5-year survival probabilities. The qRT-PCR results indicated the dissimilarities among the ten signatures in the tumor tissues and adjacent tissues of patients with CRC were fundamentally consistent with the analytical findings. Conclusions: This study comprehensively evaluated the prognostic significance of ARGs in CRC. It identified two distinct anoikis-related clusters and examined their respective immune microenvironments. Furthermore, an ARGs signature was developed to effectively predict the prognosis of CRC, thereby establishing a solid foundation for investigating the clinical prognostic role of anoikis in CRC.

Island-in-Sea Structured Pt3Fe Nanoparticles-in-Fe Single Atoms Loaded in Carbon Materials as Superior Electrocatalysts toward Alkaline HER and Acidic ORR.

In this work, Pt3Fe nanoparticles (Pt3Fe NPs) with the ordered internal structure and Pt-rich shells surrounded by plenty of Fe single atoms (Fe SAs) as active species (Pt3Fe NP-in-Fe SA) loaded in the carbon materials are successfully fabricated, which are abbreviated as island-in-sea structured (IISS) Pt3Fe NP-in-Fe SA catalysts. Moreover, the synergistic effect of O-bridging between Pt3Fe NPs and Fe SAs, and the ordered internal structured Pt3Fe NPs with Pt-rich shells of an optimal thickness contributes to the achievement of the local acidic environments on the surfaces of Pt3Fe NPs in the alkaline hydrogen evolution reaction (HER) and the enhancement of the desorption rate of *OH intermediate in the acidic oxygen reduction reaction (ORR). In addition, the electronic interactions between Pt3Fe NPs and dispersed Fe SAs cannot only provide efficient electrons transfer, but also prevent the aggregation and dissolution of Pt3Fe NPs. Furthermore, the overpotential and the half wave potential of the as-prepared IISS Pt3Fe NP-in-Fe SA catalysts toward the alkaline HER and toward the acidic ORR are 8 mV at a current density of 10 mA cm-2 and 0.933 V, respectively, which is 29 lower and 86 mV higher than those (37 mV and 0.847 V) of commercial Pt/C catalysts.

Regulating Tumor-Associated Macrophage Polarization by Cyclodextrin-Modified PLGA Nanoparticles Loaded with R848 for Treating Colon Cancer.

Purpose: This study aimed to develop a novel and feasible modification strategy to improve the solubility and antitumor activity of resiquimod (R848) by utilizing the supramolecular effect of 2-hydroxypropyl-beta-cyclodextrin (2-HP-ß-CD). Methods: R848-loaded PLGA nanoparticles modified with 2-HP-ß-CD (CD@R848@NPs) were synthesized using an enhanced emulsification solvent-evaporation technique. The nanoparticles were then characterized in vitro by several methods, such as scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, particle size analysis, and zeta potential analysis. Then, the nanoparticles were loaded with IR-780 dye and imaged using an in vivo imaging device to evaluate their biodistribution. Additionally, the antitumor efficacy and underlying mechanism of CD@R848@NPs in combination with an anti-TNFR2 antibody were investigated using an MC-38 colon adenocarcinoma model in vivo. Results: The average size of the CD@R848@NPs was 376 ± 30 nm, and the surface charge was 21 ± 1 mV. Through this design, the targeting ability of 2-HP-ß-CD can be leveraged and R848 is delivered to tumor-supporting M2-like macrophages in an efficient and specific manner. Moreover, we used an anti-TNFR2 antibody to reduce the proportion of Tregs. Compared with plain PLGA nanoparticles or R848, CD@R848@NPs increased penetration in tumor tissues, dramatically reprogrammed M1-like macrophages, removed tumors and prolonged patient survival. Conclusion: The new nanocapsule system is a promising strategy for targeting tumor, reprogramming tumor -associated macrophages, and enhancement immunotherapy.

MiR-98-5p plays suppressive effects on IL-1ß-induced chondrocyte injury associated with osteoarthritis by targeting CASP3.

BACKGROUND: This study aims to explore how miR-98-5p affects osteoarthritis, focusing on its role in chondrocyte inflammation, apoptosis, and extracellular matrix (ECM) degradation. METHODS: Quantitative real-time PCR was used to measure miR-98-5p and CASP3 mRNA levels in OA cartilage tissues and IL-1ß-treated CHON-001 cells. We predicted miR-98-5p and CASP3 binding sites using TargetScan and confirmed them via luciferase reporter assays. Chondrocyte viability was analyzed using CCK-8 assays, while pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α) were quantified via ELISA. Caspase-3 activity was examined to assess apoptosis, and Western blotting was conducted for protein marker quantification. RESULTS: Our results showed lower miR-98-5p levels in both OA cartilage and IL-1ß-stimulated cells. Increasing miR-98-5p resulted in reduced pro-inflammatory cytokines, decreased caspase-3 activity, and improved cell viability. Furthermore, miR-98-5p overexpression hindered IL-1ß-induced ECM degradation, evident from the decline in MMP-13 and ß-catenin levels, and an increase in COL2A1 expression. MiR-98-5p's impact on CASP3 mRNA directly influenced its expression. Mimicking miR-98-5p's effects, CASP3 knockdown also inhibited IL-1ß-induced inflammation, apoptosis, and ECM degradation. In contrast, CASP3 overexpression negated the suppressive effects of miR-98-5p. CONCLUSIONS: In conclusion, our data collectively suggest that miR-98-5p plays a protective role against IL-1ß-induced damage in chondrocytes by targeting CASP3, highlighting its potential as a therapeutic target for OA.

Study on the Synergistic Suppression Effect and Mechanism of N2/Ultrafine Water Mist on Liquefied Petroleum Gas Explosion.

Liquefied petroleum gas (LPG) is widely used for its cleanliness and high efficiency in industry and city life. In order to improve the suppression effect on LPG explosion, a constant volume combustion bomb was used to investigate the synergistic influence of N2/ultrafine water mist on the explosion and combustion characteristics of 6% premixed LPG/air gas. The results showed that (1) the effect of a single ultrafine water mist on suppressing LPG explosion is unstable. When the concentration of ultrafine water mist is low, the flame acceleration in the initial stage of explosion is promoted, and when the ultrafine water mist with a mass fraction of 420 g/m3 is introduced, the maximum pressure rise rate increases. (2) The combination of N2/ultrafine water mist has a synergistic effect on LPG explosion. Compared to the individual suppression effects, the combination of N2/ultrafine water mist showed more effective suppression on the explosion pressure, flame propagation, and flame instability of LPG explosion. (3) Through the mechanism analysis, it is found that the combined action of N2/ ultrafine water mist can better reduce the mole fraction and ROP peak of active free radicals such as H, O, and OH by inhibiting the main reaction of generating H, O, and OH radicals during the explosion of LPG, resulting in the reduction of flame free radicals in the explosion system, thus effectively inhibiting the chain reaction of ignition and explosion of LPG. This research can provide guidance for a better understanding and implementation of gas-liquid two-phase suppression technology for LPG explosion.

Peripheral blood syndecan-1 levels after mechanical thrombectomy can predict the clinical prognosis of patients with acute ischemic stroke.

BACKGROUND: Previously, we revealed noticeable dynamic fluctuations in syndecan-1 levels in the peripheral blood of post-stroke patients. We further investigated the clinical prognostic value of syndecan-1 as a biomarker of glycoprotein damage in patients with acute ischaemic stroke (AIS). METHODS: We examined 105 patients with acute large vessel occlusion in the anterior circulation, all of whom underwent mechanical thrombectomy (MT). Peripheral blood syndecan-1 levels were measured 1 day after MT, and patients were categorised into favourable and unfavourable prognostic groups based on the 90-day modified Rankin Scale (mRS) score. Additionally, we compared the clinical outcomes between groups with high and low syndecan-1 concentrations. RESULTS: The findings revealed a significantly lower syndecan-1 level in the group with an unfavourable prognosis compared to those with a favourable prognosis (p < 0.01). In the multivariable logistic regression analysis, lower syndecan-1 levels were identified as a predictor of unfavourable prognosis (odds ratio (OR) = 0.965, p = 0.001). Patients displaying low syndecan-1 expression in the peripheral blood (< 29.51 ng/mL) experienced a > twofold increase in the rates of unfavourable prognosis and mortality. CONCLUSIONS: Our study demonstrates that syndecan-1, as an emerging, easily detectable stroke biomarker, can predict the clinical outcomes of patients with AIS. After MT, low levels of syndecan-1 in the peripheral blood on the first day emerged as an independent risk factor for an unfavourable prognosis, suggesting that lower syndecan-1 levels might signify worse clinical presentation and outcomes in stroke patients undergoing this procedure.

Electronic excited states of monobromosilylene molecules including the spin-orbit-coupling.

We employ the internally contracted multireference configuration interaction (icMRCI-F12) with Davidson corrections to explore the electronic states of monobromosilylene molecules (HSiBr). A total of 20 states with energy up to 8.7 eV and the corresponding 50 states after taking the spin-orbit coupling (SOC) effects into account are investigated. The spectroscopic constants of the low-lying states, as well as oscillator strengths, vertical transition energies and potential energy curves (PECs) for all the 20 spin-free states and the 50 spin-orbit-coupled states of HSiBr are presented. The results indicate that the SOC effect significantly affects the dissociation pathways and the PECs of electronic excited states of HSiBr. Based on our calculation results, the interactions between the states and the dissociation of HSiBr in the UV region are discussed. Our study sheds some light on the complex interactions and dynamics of the electronic excited states of HSiBr, which would provide valuable information for future experimental investigations.

Social Network Strategies to Distribute HIV Self-testing Kits: A Global Systematic Review and Network Meta-analysis.

Introduction: Social network strategies, in which social networks are utilized to influence individuals or communities, are increasingly being used to deliver human immunodeficiency virus (HIV) interventions to key populations. We summarized and critically assessed existing research on the effectiveness of social network strategies in promoting HIV self-testing (HIVST). Methods: Using search terms related to social network interventions and HIVST, we searched five databases for trials published between January 1st, 2010, and June 30th, 2023. Outcomes included uptake of HIV testing, HIV seroconversion, and linkage to antiretroviral therapy (ART) or HIV Care. We used network meta-analysis to assess the uptake of HIV testing through social network strategies compared with control methods. A pairwise meta-analysis of studies with a comparison arm that reported outcomes was performed to assess relative risks (RR) and their corresponding 95% confidence intervals (CI). Results and discussion: Among the 3,745 manuscripts identified, 33 studies fulfilled the inclusion criteria, including one quasi-experimental study, 17 RCTs and 15 observational studies. Networks HIVST testing was organized by peers (distributed to known peers, 15 studies), partners (distributed to their sexual partners, 10 studies), and peer educators (distributed to unknown peers, 8 studies). The results showed that all of the three social network distribution strategies enhanced the uptake of HIV testing compared to standard facility-based testing. Among social networks, peer distribution had the highest uptake of HIV testing (79% probability, SUCRA 0.92), followed by partner distribution (72% probability, SUCRA 0.71), and peer educator distribution (66% probability, SUCRA 0.29). Pairwise meta-analysis showed that peer distribution (RR 2.29, 95% CI 1.54-3.39, 5 studies) and partner distribution (RR 1.45, 95% CI 1.05-2.02, 7 studies) also increased the probability of detecting HIV reactivity during testing within the key population when compared to the control. Linkage to ART or HIV Care remained comparable to facility-based testing across the three HIVST distribution strategies. Conclusions: Network-based HIVST distribution is considered effective in augmenting HIV testing rates and reaching marginalized populations compared to facility-based testing. These strategies can be integrated with the existing HIV care services, to fill the testing gap among key populations globally.PROSPERO Number: CRD42022361782.

Discovery, synthesis, and cytotoxic evaluation of isoquinolinequinones produced by Streptomyces albidoflavus derived from lichen.

Four isoquinolinequinones (1-4) were isolated from the fermentation broth of Streptomyces albidoflavus which were derived from lichens. Among them, mansouramycin H (1) was identified as a new isoquinolinequinone by comprehensive spectroscopic data analysis. The mansouramycins from S. albidoflavus presented broad cytotoxic activities, especially against MDA-MB-231, but the SAR and mechanism were still unclear. The total synthesis of mansouramycin H (1) and its twenty-three derivatives were completed and their cytotoxic activities against MDA-MB-231 were evaluated in vitro. Primary SAR revealed that the piperazine moieties introduced into the amino group at C-7 could improve the activities of mansouramycins. Benzoyl and phenylacetyl groups on piperazine fragments had better activities than those of benzyl substitution; the alkyl substituent on piperazine exhibited optimal activity. Among them, compound 1g showed the strongest cytotoxicity against MBA-MB-231 cells with an IC50 value of 5.12 ± 0.11 µM. Mechanistic studies revealed that 1g induced apoptosis in MBA-MB-231 cells through down-regulating the protein expression of Bcl-2, up-regulating the protein expression of bax, and, meanwhile, activating the cleavage of caspase-3 and caspase-9. 1g caused S phase cell cycle arrest in MBA-MB-231 cells by reducing the protein expression of CDK2 and cyclin A2 and increasing the protein levels of p21.

Whether mindfulness-guided therapy can be a new direction for the rehabilitation of patients with Parkinson's disease: a network meta-analysis of non-pharmacological alternative motor-/sensory-based interventions.

Background: The treatment for Parkinson's disease (PD) consumes a lot of manpower and financial resources. Non-pharmacological alternative motor-/sensory-based interventions are optimized for the rehabilitation of PD patients. Mindfulness-based therapy shows ideal efficacy, but the diversity of the therapy brings difficulties to the selection of clinicians and patients. Methods: Network meta-analysis in the Bayesian framework was used to evaluate the efficacy of non-pharmacological alternative motor-/sensory-based interventions in improving motor and non-motor symptoms in PD patients. Results: A total of 58 studies (2,227 patients) were included. Compared with the non-intervention group, qigong was associated with improved outcomes in the Timed Up and Go (TUG) test (mean difference (MD) -5.54, 95% confidence interval (CI) -8.28 to -2.77), and UPDRS-I (MD -15.50, 95% CI -19.93 to -7.63). Differences between non-pharmacological alternative motor-/sensory-based interventions were not significant for PDQ-39, UPDRS-I, or UPDRS-II; however, qigong was superior to dance (MD -3.91, 95% CI -6.90 to -0.95), Tai Chi (MD -3.54, 95% CI -6.53 to -0.69), acupuncture (MD -6.75, 95% CI -10.86 to -2.70), music (MD -3.91, 95% CI -7.49 to -0.48), and exercise (MD -3.91, 95% CI -6.49 to -1.33) in the TUG test. Conclusion: This network meta-analysis supports mindfulness-based therapy (e.g., qigong, yoga, and Tai Chi) as a preferred non-pharmacological alternative motor-/sensory-based intervention for PD rehabilitation. Systematic review registration: https://inplasy.com/inplasy-2022-10-0109/, INPLASY2022100109.