Association of the COL4A2 Gene Polymorphisms with Primary Intracerebral Hemorrhage Risk and Outcome in Chinese Han Population.

The relationship of single nucleotide polymorphisms (SNPs) in COL4A2 gene with risk and outcome of primary intracerebral hemorrhage (ICH) in the Chinese Han population remains unclear, which was investigated in this study. Primary ICH patients and non-stroke controls of Chinese Han ethnicity were enrolled. The genotypes of 8 tag-SNPs were determined using a custom-by-design 48-Plex SNPscan Kit. Poor 3-month outcome was defined as modified Rankin Scale score 4-6. Logistic regression was employed to examine association between COL4A2 variants and risk and poor outcome of primary ICH. 323 patients with primary ICH and 376 stroke-free controls were included. Compared to controls, the rs1049931 G and rs1049906 C alleles were associated with increased ICH risk (p = 0.027 and 0.033), and these two allele counts increased this risk after adjustments respectively (additive model: adjusted OR [aOR] 1.41, 95% CI 1.03-1.94, corrected p = 0.043; aOR 1.37, 95% CI 1.01-1.86, corrected p = 0.043). The rs1049931 AG/GG and rs1049906 CT/CC genotypes showed increased susceptibility to non-lobar hemorrhage (aOR 1.63, 95% CI 1.06-2.50, p = 0.025; aOR 1.63, 95% CI 1.07-2.47, p = 0.022). Haplotype analysis revealed an association between rs1049906-rs1049931 haplotype CG and ICH risk (OR 1.36, 95% CI 1.05-1.78, p = 0.021). Regarding clinical outcome, the rs3803230 C allele (dominant model: aOR 1.94, 95% CI 1.04-3.63, p = 0.037) and haplotype AC of rs7990214-rs3803230 (OR 1.98, 95% CI 1.13-3.46, p = 0.015) contributed to 3-month poor outcome. The COL4A2 polymorphisms are associated with an increased risk of primary ICH, mainly non-lobar hemorrhage, and with long-term poor outcome after ICH in Chinese Han population.

Assessment and solutions for vulnerability of urban rail transit network based on complex network theory: A case study of Chongqing.

As a typical complex network system, the operating environment of rail transit network (RTN) is complex and demanding. This study aims to accurate assess the weaknesses and vulnerability of RTN, which is crucial for ensuring its smooth operation. Taking Chongqing Rail Transit (CRT) as an example, this study developed a network topology model using the spatial L method and analyzed the network structure characteristics, along with the importance of key nodes under different indicators, based on complex network theory. Additionally, this study analyzed the geographical spatial distribution characteristics of nodes based on the topography and urban spatial structure of Chongqing. Then, this study classified the nodes in the RTN according to basic topological indicators, namely degree, betweenness centrality, network efficiency, and passenger flow volume (PFV). The results indicated six cluster of nodes, reflecting the variability in node vulnerability concerning overall influence (providing alternative paths, reducing path length), regional aggregation capacity, and transportation capacity. Finally, this study proposed targeted management strategies for different clusters of nodes and their respective geographical locations, providing necessary references for rational planning, safety protection, and sustainable construction of RTN.

High-Throughput Host-Microbe Single-Cell RNA Sequencing Reveals Ferroptosis-Associated Heterogeneity during Acinetobacter baumannii Infection.

Interactions between host and bacterial cells are integral to human physiology. The complexity of host-microbe interactions extends to different cell types, spatial aspects, and phenotypic heterogeneity, requiring high-resolution approaches to capture their full complexity. The latest breakthroughs in single-cell RNA sequencing (scRNA-seq) have opened up a new era of studies in host-pathogen interactions. Here, we first report a high-throughput cross-species dual scRNA-seq technology by using random primers to simultaneously capture both eukaryotic and bacterial RNAs (scRandom-seq). Using reference cells, scRandom-seq can detect individual eukaryotic and bacterial cells with high throughput and high specificity. Acinetobacter baumannii (A.b) is a highly opportunistic and nosocomial pathogen that displays resistance to many antibiotics, posing a significant threat to human health, calling for discoveries and treatment. In the A.b infection model, scRandom-seq witnessed polarization of THP-1 derived-macrophages and the intracellular A.b-induced ferroptosis-stress in host cells. The inhibition of ferroptosis by Ferrostatin-1 (Fer-1) resulted in the improvement of cell vitality and resistance to A.b infection, indicating the potential to resist related infections. scRandom-seq provides a high-throughput cross-species dual single-cell RNA profiling tool that will facilitate future discoveries in unraveling the complex interactions of host-microbe interactions in infection systems and tumor micro-environments.

Being there and being with them: the effects of visibility affordance of online short fitness video on users' intention to cloud fitness.

Introduction: Cloud fitness is transforming indoor exercise for young people in China. Recent studies have explored the correlation between media use and health-promoting behavior by examining the motivation of individuals and the credibility of influencers. However, the role of media affordance has thus far been largely overlooked. Drawing on the theory of Stimulus-Organism-Response (SOR), the study investigated the indirect effect of visibility affordance on the intention to exercise with fitness influencers in the context of cloud fitness through psychological variables. Methods: This paper, based on the online survey data (N = 456), analyses the effect of visibility affordance on the intention to fitness following with influencers. A moderated parallel mediation model was constructed to examine the relationship among related variables. Results: The paper draws the following conclusions: (1) Visibility affordance is positively related to the intention to exercise with fitness influencers. (2) Both the sense of social presence and immersion positively mediate the relationship between visibility affordance and the intention to exercise with fitness influencers. (3) The perceived popularity of the influencer positively moderates the relationship between social presence and the intention to exercise with fitness influencers and moderates the mediating role of social presence. Discussion: Consequently, this study enhances the existing body of knowledge in exercise behavior and health communication literature, and provides practical implications for short video platform, influencers and individuals in promoting healthier behaviors.

Prognostic value of the systemic inflammatory index (SII) and systemic inflammatory response index (SIRI) in patients with traumatic spinal cord injury.

PURPOSE: The overwhelming inflammatory response plays a critical role in the secondary injury cascade of traumatic spinal cord injury (tSCI). The systemic immune inflammatory index (SII) and systemic inflammatory response index (SIRI) are two novel inflammatory biomarkers. The SII was calculated based on lymphocyte, neutrophil, and platelet counts, while the SIRI was calculated based on lymphocyte, neutrophil, and monocyte counts. Their prognostic value in patients with tSCI remains unclear. METHODS: Patients with tSCI admitted within 24 h of trauma were retrospectively and consecutively enrolled. Peripheral blood samples were collected on admission. The primary outcome was American Spinal Injury Association Impairment Scale (AIS) grade conversion at discharge. Multivariable logistic regression analysis was performed to determine the relationship between SII and SIRI and AIS grade conversion. We performed receiver operating characteristic curve (ROC) analysis to assess the discriminative ability of SII, and SIRI in predicting AIS grade conversion. RESULTS: Among 280 included patients, 77 (27.5%) had improved AIS grade conversion at discharge. After adjustment for confounders, SII was independently associated with AIS grade conversion (per SD, odds ratio [OR], 0.68; 95% confidence interval [CI] 0.47-0.98, p = 0.040), while the association between SIRI and AIS grade conversion was insignificant (per 1 SD, OR, 0.77; 95% CI 0.55-1.08, p = 0.130). The ROC analysis revealed that the SII had the best predictive value for AIS grade conversion (area under curve: 0.608, 95% CI 0.536-0.678). CONCLUSIONS: Increased SII was independently associated with a decreased likelihood of improved AIS grade conversion.

Comparison of Characteristics and Outcomes Between Acute Ischemic Stroke Patients with Different Types of Heart Failure.

Acute ischemic stroke (AIS) can be complicated by heart failure involving preserved ejection fraction (HFpEF) or reduced ejection fraction (HFrEF), and whether or not the prognosis differs between the 2 types of patients remains unclear. We compared the clinical characteristics and outcomes of the 2 types of patients at 3 months after the stroke.We retrospectively analyzed patients who, between 1 January 2018 and 1 January 2021, experienced AIS that was complicated by HFrEF or HFpEF. All patients had been prospectively registered in the Chengdu Stroke Registry. Poor outcome was defined as a modified Rankin Scale (mRS) score of 2-6 at 3 months. Univariate and binary logistic regression was used to assess whether HFpEF was associated with a significantly worse prognosis than HFrEF.Among the final sample of 108 patients (60.2% men; mean age, 73.08 ± 10.82 years), 75 (69.4%) had HFpEF. Compared to HFrEF patients, those with HFpEF were older (P = 0.002), were more likely to have chronic kidney disease (P = 0.033), and were more likely to experience a poor outcome (P = 0.022). After adjustments, HFpEF was associated with significantly greater risk of poor outcome than HFrEF (OR 4.13, 95%CI 1.20-15.79, P = 0.029). However, rates of hemorrhagic transformation or mortality at 3 months after AIS did not differ significantly between the 2 types of heart failure (all P > 0.05).Patients with AIS involving HFpEF experience worse outcomes than those with HFrEF and therefore may require special monitoring and management. Our findings need to be verified in large prospective studies.

Massive Hemorrhage Following Acupuncture Treatment in a Neurofibromatosis Type 1 Patient.

Neurofibromatosis type 1 (NF1) is a genetic disorder involving multiple organs. Vascular involvement is a rare complication among NF1 patients. We report a case of a 59-year-old female NF1 patient who presented with a massive hematoma over the scapular area after undergoing acupuncture treatment. Contrast-enhanced CT and MRI demonstrated a slightly hyperdense mass measuring 24.2 × 10.3 cm in size, and multiple enlarged and tortuous malformed vessels were seen arising from the left subclavian artery. Arterial embolization and subsequent surgical mass resection were successfully performed. This case indicates that minor injuries such as acupuncture-related ones could cause severe hemorrhage in patients with vascular malformation related to NF1. Endovascular angiography and embolization proved to be effective in localizing the culprit vessel and stopping active bleeding in our patient.

The attitudes of postgraduate medical students towards the curriculum by degree type: a large-scale questionnaire survey.

BACKGROUND: Chinese medical schools have offered both professional and academic degrees for postgraduate students. However, there is limited information about the attitudes of professional-degree and academic-degree students. We aimed to examine the attitudes of full-time postgraduate students towards the curriculum, stratified by degree type. METHODS: A 29-item online questionnaire was distributed to postgraduate students in West China School of Medicine of Sichuan University in 2020. The questionnaire was designed to collect students' demographic characteristics, attitudes towards curricular provision and content, and classroom organization. A comparison was made between groups based on degree type (academic degree versus professional degree). RESULTS: Overall, 645 out of 908 students at West China School of Medicine completed the questionnaire. Comparing with students pursuing academic degrees, professional-degree students were more interested if the curriculum included specialized knowledge and clinical skills, and expressed concerns over the excessive compulsory courses and inadequate optional courses (p < 0.001), particularly prominent among first-year postgraduate students. Besides, a greater proportion of professional-degree students thought the curriculum was conflict with clinical work to some extent, and they also rated taking attendance in class as less reasonable (p < 0.01). Conversely, students pursuing academic degrees expressed that the courses were inadequate in interdisciplinary curriculum and had some crossover or repetition, and they assigned a higher importance rating for the curriculum when comparing professional-degree students (all p < 0.05). CONCLUSIONS: Different attitudes toward the curriculum are observed between students pursuing professional degrees and those pursuing academic degrees. This study provides benchmark data for future postgraduate course reforms in China.

The association between hypertensive angiopathy and cerebral amyloid angiopathy in primary intracerebral hemorrhage.

Objective: To determine the association between the burden of cerebral small vessel disease (CSVD) due to hypertensive angiopathy (HA) and cerebral amyloid angiopathy (CAA) on MRI in patients with primary intracerebral hemorrhage (ICH). Methods: Patients with primary ICH admitted to our center from March 2012 to November 2021 were consecutively enrolled. We used multivariate binary and ordinal regression analyses to assess the association between HA-CSVD burden and CAA-CSVD burden. Lobar cerebral microbleeds (CMBs) were categorized into three level of severity: 0-1, 2-4, and ≥ 5 lobar CMBs. A high CAA-CSVD score was defined as a CAA-CSVD score of ≥3. Results: Overall, 222 participants (mean age 59.88 ± 13.56) were included into analysis. Age and ICH etiology differed among different lobar CMB severity and between the presence and absence of high CAA-CSVD score (all p < 0.05). Positive associations between HA-related markers and both lobar CMB severity and high CAA-CSVD score (p < 0.05 for the presence of lacune, deep CMBs ≥5, the presence of WMH, and HA-CSVD score) were observed in univariate analysis. These associations remained significant after adjusting for age, sex, ICH etiology, and potential vascular risk factors. The distribution of CAA-CSVD score was significantly different between patients with and without CMBs ≥5 (adjusted OR 2.351, 95% CI 1.242-4.455, p = 0.009) after correcting for age, sex, ICH etiology, and vascular risk factors. Conclusion: Our study provides evidence of an association between HA-CSVD and CAA-CSVD in patients with primary ICH, which needs to be verified in future studies.

A Carbene Relay Strategy for Cascade Insertion Reactions.

Insertion reactions that involve stabilized electrophilic metallocarbenes are of great importance for installing α-heteroatoms to carbonyl compounds. Nevertheless, the limited availability of carbene precursors restricts the introduction of only a single heteroatom. In this report, we describe a new approach based on an I(III) /S(VI) reagent that promotes the cascade insertion of heteroatoms. This is achieved by sequentially generating two α-heteroatom-substituted metal carbenes in one reaction. We found that this mixed I(III) /S(VI) ylide reacts efficiently with a transition metal catalyst and an X-H bond (where X=O, N). This transformation leads to the sequential formation of a sulfoxonium- and an X-substituted Rh-carbenes, enabling further reactions with another Y-H bond. Remarkably, a wide range of symmetrical and unsymmetrical α,α-O,O-, α,α-O,N-, and α,α-N,N-subsituted ketones can be prepared under mild ambient conditions. In addition, we successfully demonstrated other cascades, such as CN/CN double amidation, C-H/C-S double insertion, and C-S/Y-H double insertion (where Y=S, N, O, C). Notably, the latter two cascades enabled the simultaneous installation of three functional groups to the α-carbon of carbonyl compounds in a single step. These reactions demonstrate the versatility of our approach, allowing for the synthesis of ketones and esters with multiple α-heteroatoms using a common precursor.

Construction and Application of Large Stokes-Shift Organic Room Temperature Phosphorescence Materials by Intermolecular Charge Transfer.

Notably, the intermolecular charge transfer between pyrene (Py) and benzophonenes (BPs) can significantly enhance the quantum yield of the triplet state of Py, which will convert Py from a fluorescence molecule to a phosphorescence molecule. The intermolecular charge transfer is confirmed by steady-state and time-resolved spectroscopy and theoretical study. Based on these foundations, Py is doped into BPs systems and a large Stokes-shift organic room temperature phosphorescence (ORTP) is observed. By using different benzophenone derivatives, a series of host-guest ORTP materials with different luminescent properties adjusted by intermolecular charge transfer features are developed. Fortunately, these host-guest ORTP systems from benzophenone derivatives and pyrene are readily fabricated, and the red gradient color lasting as long as 3 s is observed after removing UV excitation. This host-guest charge transfer strategy plays an important role in the mechanism of the luminous type shift. Our strategy paves the way to design ORTP materials conveniently and apply these materials in encryption and temperature alarm device.

Pathological Changes of Small Vessel Disease in Intracerebral Hemorrhage: a Systematic Review and Meta-analysis.

In intracerebral hemorrhage (ICH) with pathology-proven etiology, we performed a systematic review and meta-analysis to elucidate the association between cerebral amyloid angiopathy (CAA) and arteriolosclerosis, and directly compared MRI and pathological changes of markers of cerebral small vessel disease (CSVD). Studies enrolling primary ICH who had received an etiological diagnosis through biopsy or autopsy were searched using Ovid MEDLINE, PubMed, and Web of Science from inception to June 8, 2022. We extracted pathological changes of CSVD for each patient whenever available. Patients were grouped into CAA + arteriolosclerosis, strict CAA, and strict arteriolosclerosis subgroups. Of 4155 studies identified, 28 studies with 456 ICH patients were included. The frequency of lobar ICH (p<0.001) and total microbleed number (p=0.015) differed among patients with CAA + arteriolosclerosis, strict CAA, and strict arteriolosclerosis. Concerning pathology, severe CAA was associated with arteriolosclerosis (OR 6.067, 95% CI 1.107-33.238, p=0.038), although this association was not statistically significant after adjusting for age and sex. Additionally, the total microbleed number (median 15 vs. 0, p=0.006) was higher in ICH patients with CAA evidence than those without CAA. The pathology of CSVD imaging markers was mostly investigated in CAA-ICH. There was inconsistency concerning CAA severity surrounding microbleeds. Small diffusion-weighted imaging lesions could be matched to acute microinfarct histopathologically. Studies that directly correlated MRI and pathology of lacunes, enlarged perivascular spaces, and atrophy were scarce. Arteriolosclerosis might be associated with severe CAA. The pathological changes of CSVD markers by ICH etiology are needed to be investigated further.

High-throughput single nucleus total RNA sequencing of formalin-fixed paraffin-embedded tissues by snRandom-seq.

Formalin-fixed paraffin-embedded (FFPE) tissues constitute a vast and valuable patient material bank for clinical history and follow-up data. It is still challenging to achieve single cell/nucleus RNA (sc/snRNA) profile in FFPE tissues. Here, we develop a droplet-based snRNA sequencing technology (snRandom-seq) for FFPE tissues by capturing full-length total RNAs with random primers. snRandom-seq shows a minor doublet rate (0.3%), a much higher RNA coverage, and detects more non-coding RNAs and nascent RNAs, compared with state-of-art high-throughput scRNA-seq technologies. snRandom-seq detects a median of >3000 genes per nucleus and identifies 25 typical cell types. Moreover, we apply snRandom-seq on a clinical FFPE human liver cancer specimen and reveal an interesting subpopulation of nuclei with high proliferative activity. Our method provides a powerful snRNA-seq platform for clinical FFPE specimens and promises enormous applications in biomedical research.

Electrochemically-promoted synthesis of benzo[b]thiophene-1,1-dioxides via strained quaternary spirocyclization.

We report an approach for the synthesis of benzothiophene motifs under electrochemical conditions by the reaction of sulfonhydrazides with internal alkynes. Upon the formation of a quaternary spirocyclization intermediate by the selective ipso-addition instead of an ortho-attack, the S-migration process was rationalized to lead to the products. Computational studies revealed the selectivity and the compatibility of drug molecules showcased the potential application of the protocols.

C-H Fluoroalkylsulfinylation/Intramolecular Rearrangement for Precise Synthesis of Fluoroalkyl Sulfoxides.

An efficient methodology to access various fluoroalkyl sulfoxides bearing ortho/para-functionalized amine scaffolds from arylhydroxylamines is described. The transformation was featured with new electrophilic trifluoromethylthiolated reagents, good functional group tolerance, and late-stage modification of complex bioactive scaffolds, providing a rapid access to prepare numerous trifluoromethyl- and difluoromethyl-substituted sulfoxides. Mechanism studies and density functional theory calculations suggest this reaction goes through a nucleophilic trifluoromethylthiolation of arylhydroxylamine and subsequent internal 2,3-sigmatropic rearrangement involving a sulfur and oxygen transfer process.

Evaluating the influence of common antibiotics on the efficacy of a recombinant immunotoxin in tissue culture.

OBJECTIVE: Recombinant immunotoxins (RITs) are antibody-toxin fusion proteins that can selectively eliminate populations of cells expressing specific surface receptors. They are in evaluation as therapeutic agents for cancer. RITs based on Pseudomonas exotoxin A (PE) are in use clinically for the treatment of hairy cell leukemia, and under trial for the treatment of other cancers. In an effort to improve the efficacy of PE-based RITs, we evaluated the potential of combination therapy with several common antibiotics (tetracycline, chloramphenicol, streptomycin, linezolid, fusidic acid, and kanamycin) on human cell lines HEK293, OVCAR8, and CA46. Antibiotics were selected based on their potential to inhibit mitochondrial protein synthesis and disrupt energy metabolism in cancer cells. RESULTS: Tetracycline, chloramphenicol, linezolid, and fusidic acid alone killed cultured human cells at high concentrations. At high but nontoxic concentrations of each antibiotic, only chloramphenicol treatment of the Burkitt's lymphoma cell line CA46 showed enhanced cytotoxicity when paired with an anti-transferrin receptor/PE RIT. This result, however, could not be replicated in additional Burkitt's lymphoma cell lines Ramos and Raji. Although the six antibiotics we tested are not promising candidates for RIT combination therapy, we suggest that fusidic acid could be considered independently as a potential cancer therapeutic.

Enhanced NADH Metabolism Involves Colistin-Induced Killing of Bacillus subtilis and Paenibacillus polymyxa.

The commonly believed mechanism of colistin against Gram-negative bacteria is to cause cell membrane lysis, whereas the mechanism of colistin against Gram-positive bacteria is extremely fragmented. In this study, we found that colistin treatment on Bacillus subtilis WB800, Paenibacillus polymyxa C12 and Paenibacillus polymyxa ATCC842 enhances not only the activities of α-ketoglutaric dehydrogenase and malate dehydrogenase in tricarboxylic acid (TCA) cycle, but also the relative expression levels of their encoding genes. Additionally, the oxaloacetate concentration also increases. Interestingly, the analysis of the relative expression of genes specific for respiratory chain showed that colistin treatment stimulates the respiratory chain in Gram-positive bacteria. Accordingly, the NAD⁺/NADH ratio increases and the oxidative level is then boosted up. As a result, the intensive oxidative damages are induced in Gram-positive bacteria and cells are killed. Notably, both rotenone and oligomycin, respectively, inhibiting NADH dehydrogenase and phosphorylation on respiratory chain can downgrade oxidative stress formation, thus alleviating the colistin-induced killing of Gram-positive cells. Besides, thiourea-based scavenging for reactive oxygen species also rescues the colistin-subjected cells. These data collectively demonstrate that colistin stimulates both TCA cycle and respiratory chain in Gram-positive bacteria, leading to the enhancement of NADH metabolism and resulting in the generation of oxidative damages in Gram-positive cells. Our studies provide a better understanding of antibacterial mechanism of colistin against Gram-positive bacteria, which is important for knowledge on bacterial resistance to colistin happening via the inhibition of respiratory chain and manipulation of its production.

Oxidative Stress Induced by Polymyxin E Is Involved in Rapid Killing of Paenibacillus polymyxa.

Historically, the colistin has been thought to kill bacteria through membrane lysis. Here, we present an alternative mechanism that colistin induces rapid Paenibacillus polymyxa death through reactive oxygen species production. This significantly augments our understanding of the mechanism of colistin action, which is critical knowledge toward the yield development of colistin in the future.

PCDD/Fs distribution characteristics and health risk assessment in fly ash discharged from MSWIs in China.

This study provided distribution and health risk information of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in fly ash from 4 municipal solid waste incinerators (MSWIs) in four seasons from four sites, including Zhengzhou City in Henan Province, Chuzhou City in Anhui Province, Jilin City in Jilin Province and Zibo City in Shandong Province. The toxic equivalent concentration (I-TEQ) values of PCDD/Fs ranged from 0.0707 to 0.7742ng I-TEQ/g, and no identical sequence occurred during four seasons in different sampling sites. The stabilization process might efficiently reduce the content and toxicology of PCDD/Fs in fly ash. The value of PCDD/PCDF in fly ash ranged from 0.145 to 0.787 after solidification. The characteristic index (DCI) of 2,3,4,7,8-P5CDF was 0.803 with 6.6% under 95% probability for fly ash samples discharged from MSWIs. The 95th percentile carcinogenic risks (CRs) for onsite workers were lower than the threshold value (10-5), suggesting that the cancer risk levels of PCDD/Fs in fly ash for onsite workers were acceptable. The 95th percentile non-carcinogenic risks (non-CRs) for onsite workers were lower than 1, suggesting no obvious non-carcinogenic effect was developed for onsite workers. This paper provide an overview information on the distribution of PCDD/Fs in fly ash during four seasons, and it could be used as an important fingerprint to distinguish the fly ash sources. Thus, the research could provide basic information for fly ash management in environment.