Within-host evolutionary dynamics and tissue compartmentalization during acute SARS-CoV-2 infection.

The global evolution of SARS-CoV-2 depends in part upon the evolutionary dynamics within individual hosts with varying immune histories. To characterize the within-host evolution of acute SARS-CoV-2 infection, we sequenced saliva and nasal samples collected daily from vaccinated and unvaccinated individuals early during infection. We show that longitudinal sampling facilitates high-confidence genetic variant detection and reveals evolutionary dynamics missed by less-frequent sampling strategies. Within-host dynamics in both unvaccinated and vaccinated individuals appeared largely stochastic; however, in rare cases, minor genetic variants emerged to frequencies sufficient for forward transmission. Finally, we detected significant genetic compartmentalization of viral variants between saliva and nasal swab sample sites in many individuals. Altogether, these data provide a high-resolution profile of within-host SARS-CoV-2 evolutionary dynamics.IMPORTANCEWe detail the within-host evolutionary dynamics of SARS-CoV-2 during acute infection in 31 individuals using daily longitudinal sampling. We characterized patterns of mutational accumulation for unvaccinated and vaccinated individuals, and observed that temporal variant dynamics in both groups were largely stochastic. Comparison of paired nasal and saliva samples also revealed significant genetic compartmentalization between tissue environments in multiple individuals. Our results demonstrate how selection, genetic drift, and spatial compartmentalization all play important roles in shaping the within-host evolution of SARS-CoV-2 populations during acute infection.

Changes in Microbial Composition During the Succession of Biological Soil Crusts in Alpine Hulun Buir Sandy Land, China.

Biological soil crusts (biocrusts) are considered "desert ecosystem engineers" because they play a vital role in the restoration and stability maintenance of deserts, including those cold sandy land ecosystems at high latitudes, which are especially understudied. Microorganisms participate in the formation and succession of biocrusts, contributing to soil properties' improvement and the stability of soil aggregates, and thus vegetation development. Accordingly, understanding the composition and successional characteristics of microorganisms is a prerequisite for analyzing the ecological functions of biocrusts and related applications. Here, the Hulun Buir Sandy Land region in northeastern China-lying at the highest latitude of any sandy land in the country-was selected for study. Through a field investigation and next-generation sequencing (Illumina MiSeq PE300 Platform), our goal was to assess the shifts in diversity and community composition of soil bacteria and fungi across different stages during the succession of biocrusts in this region, and to uncover the main factors involved in shaping their soil microbial community. The results revealed that the nutrient enrichment capacity of biocrusts for available nitrogen, total nitrogen, total phosphorus, total content of water-soluble salt, available potassium, soil organic matter, and available phosphorus was progressively enhanced by the succession of cyanobacterial crusts to lichen crusts and then to moss crusts. In tandem, soil bacterial diversity increased as biocrust succession proceeded but fungal diversity decreased. A total of 32 bacterial phyla and 11 fungal phyla were identified, these also known to occur in other desert ecosystems. Among those taxa, the relative abundance of Proteobacteria and Cyanobacteria significantly increased and decreased, respectively, along the cyanobacterial crust-lichen-moss crust successional gradient. However, for Actinobacteria, Chloroflexi, and Acidobacteria their changed relative abundance was significantly hump-shaped, increasing in the shift from cyanobacterial crust to lichen crust, and then decreasing as lichen crust shifted to moss crust. In this process, the improved soil properties effectively enhanced soil bacterial and fungal community composition. Altogether, these findings broaden our understanding about how soil microbial properties can change during the succession of biocrusts in high-latitude, cold sandy land ecosystems.

Longitudinal patient-reported outcomes after minimally invasive McKeown esophagectomy for patients with esophageal squamous cell carcinoma.

PURPOSE: Surgery for esophageal squamous cell carcinoma (ESCC) is characterized by a poor prognosis and high complication rate, resulting in a heavy symptom burden and poor health-related quality of life (QOL). We evaluated longitudinal patient-reported outcomes (PROs) to analyze the correlations between symptoms and QOL and their changing characteristics during postoperative rehabilitation. METHODS: We investigated patients with ESCC who underwent minimally invasive McKeown esophagectomy at Sichuan Cancer Hospital between April 2019 and December 2019. Longitudinal data of the clinical characteristics and PROs were collected. The MD Anderson Symptom Inventory and European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaires were used to assess symptoms and QOL and compare the trajectories of PROs during the investigation. RESULTS: A total of 244 patients with ESCC were enrolled in this study. Regarding QOL, role and emotional functions returned to baseline at 1 month after surgery, and cognitive and social functions returned to baseline at 3 months after surgery. However, physical function and global QOL did not return to baseline at 1 year after surgery. At 7 days and 1, 3, 6, and 12 months after surgery, the main symptoms of the patients were negatively correlated with physical, role, emotional, cognitive, and social functions and the overall health status (P < 0.05). CONCLUSION: Patients with ESCC experience reduced health-related QOL and persisting symptoms after minimally invasive McKeown esophagectomy, but a recovery trend was observed within 1 month. The long-term QOL after esophagectomy is acceptable.

Sensitive and Visual Detection of Brassica Yellows Virus Using Reverse Transcription Loop-Mediated Isothermal Amplification-Coupled CRISPR-Cas12 Assay.

Brassica yellows virus (BrYV) is an economically important virus on cruciferous species. In this study, a one-pot reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay coupled with the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a system was developed for the detection of BrYV. The limit of detection of this method reached 32.8 copies of the BrYV ORF5, which is 100-fold more sensitive than the RT-LAMP method. Moreover, there was no cross-reactivity with other rapeseed-infecting RNA viruses or poleroviruses. We dried the CRISPR/Cas12a reagent in a trehalose and pullulan mixture to retain its efficacy at the RT-LAMP temperature of 63°C in order to allow portable BrYV detection in a water bath. The entire process can be performed in about 1 h, and a positive result can be rapidly and conveniently detected using a handheld UV lamp. In the field, the RT-LAMP-CRISPR/Cas12a assay was accurate and had higher sensitivity than RT-LAMP and reverse transcription-polymerase chain reaction assays. The novel RT-LAMP-CRISPR/Cas12a assay allows convenient, portable, rapid, low-cost, highly sensitive, and specific detection of BrYV and has great potential for on-site monitoring of BrYV.

Radiological characteristics predicting early poor drug response in patients with hemifacial spasm.

OBJECTIVES: Patients with hemifacial spasm (HFS) often resort to botulinum toxin injections or microvascular decompression surgery when medication exhibits limited effectiveness. This study aimed to identify MRI and demographic factors associated with poor drug response at an early stage in patients with HFS. METHODS: We retrospectively included patients with HFS who underwent pre-therapeutic MRI examination. The presence, location, severity, and the offending vessels of neurovascular compression were blindly evaluated using MRI. Drug responses and clinical data were obtained from the medical notes or phone follow-ups. Logistic regression analysis was performed to identify potential factors. RESULTS: A total of 116 patients were included, with an average age at the time of first examination of 50.4 years and a median duration of onset of 18 months. Forty-nine (42.2%) patients reported no symptom relief. Thirty-seven (31.9%) patients reported poor symptom relief. Twenty-two (19.0%) patients reported partial symptom relief. Eight (6.9%) patients achieved complete symptom relief. The factors that were statistically significant associated with poor drug responses were contact in the attach segment of the facial nerve and aged 70 and above, with an odds ratio of 7.772 (p = 0.002) and 0.160 (p = 0.028), respectively. CONCLUSIONS: This study revealed that mild compression in the attach segment of the facial nerve in pre-therapeutic MRI increases the risk of poor drug responses in patients with HFS, while patients aged 70 and above showed a decreased risk. These findings may assist clinician to choose optimal treatment at an early stage.

Stroke Following Coronavirus Disease 2019 Vaccination: Evidence Based on Different Designs of Real-World Studies.

BACKGROUND: We aimed to evaluate whether coronavirus disease 2019 (COVID-19) vaccination was associated with stroke. METHODS: We conducted a systematic meta-analysis of studies using cohort, self-controlled case series (SCCS), and case-crossover study (CCOS) designs to evaluate incidence risk ratios (IRRs) and 95% confidence intervals (CIs) of ischemic stroke (IS), hemorrhagic stroke (HS), and cerebral venous sinus thrombosis (CVST) following COVID-19 vaccination. Risks of stroke were pooled among subpopulations categorized by vaccine type, dose, age, and sex. Sensitivity analysis was performed by different defined risk periods. RESULTS: Fourteen studies involving 79 918 904 individuals were included. Cohort studies showed decreased risks of IS (IRR, 0.82 [95% CI, .75-.90]) and HS (IRR, 0.75 [95% CI, .67-.85]) postvaccination, but not CVST (IRR, 1.18 [95% CI, .70-1.98]). SCCS identified increased risks 1-21 days postvaccination (IRRIS, 1.05 [95% CI, 1.00-1.10]; IRRHS, 1.16 [95% CI, 1.06-1.26]) or 1-28 days postvaccination (IRRIS, 1.04 [95% CI, 1.00-1.08]; IRRHS, 1.37 [95% CI, 1.15-1.64]), similar to CVST (IRR, 1.58 [95% CI, 1.08-2.32]). CCOS reported an increased risk of CVST after ChAdOx1 vaccination (IRR, 2.9 [95% CI, 1.1-7.2]). CONCLUSIONS: Although different study designs yielded inconsistent findings, considering the relatively low background incidence of stroke and benefits of vaccination, even a potentially increased risk of stroke postvaccination should not justify vaccine hesitancy.

Characterizing SARS-CoV-2 Transcription of Subgenomic and Genomic RNAs During Early Human Infection Using Multiplexed Droplet Digital Polymerase Chain Reaction.

BACKGROUND: Control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission requires understanding SARS-CoV-2 replication dynamics. METHODS: We developed a multiplexed droplet digital polymerase chain reaction (ddPCR) assay to quantify SARS-CoV-2 subgenomic RNAs (sgRNAs), which are only produced during active viral replication, and discriminate them from genomic RNAs (gRNAs). We applied the assay to specimens from 144 people with single nasopharyngeal samples and 27 people with >1 sample. Results were compared to quantitative PCR (qPCR) and viral culture. RESULTS: sgRNAs were quantifiable across a range of qPCR cycle threshold (Ct) values and correlated with Ct values. The ratio sgRNA:gRNA was stable across a wide range of Ct values, whereas adjusted amounts of N sgRNA to a human housekeeping gene declined with higher Ct values. Adjusted sgRNA and gRNA amounts were quantifiable in culture-negative samples, although levels were significantly lower than in culture-positive samples. Daily testing of 6 persons revealed that sgRNA is concordant with culture results during the first week of infection but may be discordant with culture later in infection. sgRNA:gRNA is constant during infection despite changes in viral culture. CONCLUSIONS: Ct values from qPCR correlate with active viral replication. More work is needed to understand why some cultures are negative despite presence of sgRNA.

Impact of Severe Acute Respiratory Syndrome Coronavirus 2 Variants on Inpatient Clinical Outcome.

BACKGROUND: Prior observation has shown differences in COVID-19 hospitalization risk between SARS-CoV-2 variants, but limited information describes hospitalization outcomes. METHODS: Inpatients with COVID-19 at 5 hospitals in the eastern United States were included if they had hypoxia, tachypnea, tachycardia, or fever, and SARS-CoV-2 variant data, determined from whole-genome sequencing or local surveillance inference. Analyses were stratified by history of SARS-CoV-2 vaccination or infection. The average effect of SARS-CoV-2 variant on 28-day risk of severe disease, defined by advanced respiratory support needs, or death was evaluated using models weighted on propensity scores derived from baseline clinical features. RESULTS: Severe disease or death within 28 days occurred for 977 (29%) of 3369 unvaccinated patients and 269 (22%) of 1230 patients with history of vaccination or prior SARS-CoV-2 infection. Among unvaccinated patients, the relative risk of severe disease or death for Delta variant compared with ancestral lineages was 1.30 (95% confidence interval [CI]: 1.11-1.49). Compared with Delta, the risk for Omicron patients was .72 (95% CI: .59-.88) and compared with ancestral lineages was .94 (.78-1.1). Among Omicron and Delta infections, patients with history of vaccination or prior SARS-CoV-2 infection had half the risk of severe disease or death (adjusted hazard ratio: .40; 95% CI: .30-.54), but no significant outcome difference by variant. CONCLUSIONS: Although risk of severe disease or death for unvaccinated inpatients with Omicron was lower than with Delta, it was similar to ancestral lineages. Severe outcomes were less common in vaccinated inpatients, with no difference between Delta and Omicron infections.

M2 macrophage marker CHI3L2 could serve as a potential prognostic and immunological biomarker in glioma by integrated single-cell and bulk RNA-Seq analysis.

BACKGROUND: CHI3L2 plays a crucial role in multiple cancers, but its importance in glioma remains unclear. Hence, we comprehensively integrated bulk RNA-sequencing (RNA-seq), proteomics and single-cell RNA-seq (scRNA-seq) to determine the roles of CHI3L2 in gliomas. METHODS: Bulk RNA-seq, proteomics and scRNA-seq data of CHI3L2 in glioma were obtained from online databases. The quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) were conducted to verify the CHI3L2 expression. Then, univariate and multivariate Cox regression analyses, Norman charts and gene set enrichment analysis (GSEA) were performed. Finally, the associations between CHI3L2 and tumor immunity were explored. RESULTS: The expression of CHI3L2 was markedly higher in glioma cancers compared with normal tissues from analysis of the data of the Cancer Genome Atlas and Chinese Glioma Genome Atlas datasets and as verified by GSE4290, GSE50161, qRT-PCR and IHC results (p < 0.05). High expression of CHI3L2 suggested poor overall survival (OS) prognosis in gliomas (p < 0.05). CHI3L2 might also serve as an independent predictor of OS for gliomas (p < 0.05) and we also constructed a Norman chart to predict these patients' survival prognosis with good performance. GSEA analysis showed that CHI3L2 might be involved with eight pathways in gliomas. Regarding tumor immunity, CHI3L2 was found to be significantly involved with immune cell infiltration levels of low-grade glioma, the tumor immune microenvironment, immune checkpoints and immune cells in both low-grade glioma and glioblastoma (p < 0.05). Additionally, scRNA-seq data for CHI3L2 in glioma from the TISCH2 website showed that CHI3L2 is mainly expressed in astrocytes, endothelial cells, CD8+ T cells, mono/macrophage cells, etc. CONCLUSIONS: CHI3L2 presents prognostic and immunological values in glioma, providing novel therapeutic targets for glioma patients.

Functional reconstruction of the impaired cortex and motor function by hMGEOs transplantation in stroke.

Stroke is the leading cause of death and long-term disability worldwide. But treatments are not available to promote functional recovery, and efficient therapies need to be investigated. Stem cell-based therapies hold great promise as potential technologies to restore function in brain disorders. Loss of GABAergic interneurons after stroke may result in sensorimotor defects. Here, by transplanting human brain organoids resembling the MGE domain (human MGE organoids, hMGEOs) derived from human induced pluripotent stem cells (hiPSCs) into the infarcted cortex of stroke mice, we found that grafted hMGEOs survived well and primarily differentiated into GABAergic interneurons and significantly restored the sensorimotor deficits of stroke mice for a long time. Our study offers the feasibility of stem cell replacement therapeutics strategy for stroke.

DPY30 promotes colorectal carcinoma metastasis by upregulating ZEB1 transcriptional expression.

DPY30 belongs to the core subunit of components of the histone lysine methyltransferase complex, which is implicated in tumorigenesis, cell senescence, and other biological events. However, its contribution to colorectal carcinoma (CRC) progression and metastasis has yet to be elucidated. Therefore, this study aimed to investigate the biological function of DPY30 in CRC metastasis both in vitro and in vivo. Herein, our results revealed that DPY30 overexpression is significantly positively correlated with positive lymph nodes, epithelial-mesenchymal transition (EMT), and CRC metastasis. Moreover, DPY30 knockdown in HT29 and SW480 cells markedly decreased EMT progression, as well as the migratory and invasive abilities of CRC cells in vitro and lung tumor metastasis in vivo. Mechanistically, DPY30 increased histone H3K4me3 level and promoted EMT and CRC metastasis by upregulating the transcriptional expression of ZEB1. Taken together, our findings indicate that DPY30 may serve as a therapeutic target and prognostic marker for CRC.

Predictive performance of the perivascular fat attenuation index for interventional antegrade percutaneous coronary intervention for chronic total occlusion.

OBJECTIVES: This study aimed to investigate the association between the perivascular fat attenuation index (FAI) and the success of the antegrade percutaneous coronary intervention (PCI) for chronic total occlusion (CTO). METHODS: This study evaluated patients with only one CTO lesion observed on conventional coronary angiography (CAG) who underwent coronary computed tomography angiography (CCTA) < 1 month before CAG, from 2018 to 2019. The clinical data, CCTA-based CTO lesion morphologic characteristics, and perivascular FAI of CTO lesions were recorded and analysed. RESULTS: In total, 156 patients with CTOs were enrolled in this study. Successful antegrade PCI (A-PCI) was achieved in 105 CTO lesions (67.3%). The perivascular FAI of the failed A-PCI group was significantly lower than the successful A-PCI group (-84.76 ± 10.44 Hounsfield unit (HU) vs. -67.54 ± 9.94 HU; p < 0.001), and the cut-off value determined by the receiver operating characteristic (ROC) curve was -77.50 HU. Multivariable analysis revealed no statistical significance in the clinical data, FAI ≤ -77.50 HU (odds ratio (OR): 33.96), negative remodeling (OR: 4.36), severe calcification degree (OR: 4.43) and occlusion length ≥ 20.25 mm (OR: 3.89) were independent predictors of A-PCI failure. The prediction performance of combining the three morphologic characteristics (severe calcification, occlusion length ≥ 20.25 mm, and negative remodeling) with FAI ≤ -77.50 HU was better than that of the three morphologic characteristics alone (0.93 versus 0.77, p < 0.001). CONCLUSIONS: As a non-invasive index for detecting coronary inflammation, FAI complements indicators based on coronary CTA well and may be helpful for choosing appropriate interventional strategies. KEY POINTS: • Perivascular FAI of CTO was significantly higher in the failed A-PCI group. • The combination of FAI with other morphological predictors showed higher predictive performance of failed A-PCI for CTOs. • FAI is a good complement to indicators based on coronary CTA.

A map of the spatial distribution and tumour-associated macrophage states in glioblastoma and grade 4 IDH-mutant astrocytoma.

Tumour-associated macrophages (TAMs) abundantly infiltrate high-grade gliomas and orchestrate immune response, but their diversity in isocitrate dehydrogenase (IDH)-differential grade 4 gliomas remains largely unknown. This study aimed to dissect the transcriptional states, spatial distribution, and clinicopathological significance of distinct monocyte-derived TAM (Mo-TAM) and microglia-derived TAM (Mg-TAM) clusters across glioblastoma-IDH-wild type and astrocytoma-IDH-mutant-grade 4 (Astro-IDH-mut-G4). Single-cell RNA sequencing was performed on four cases of human glioblastoma and three cases of Astro-IDH-mut-G4. Cell clustering, single-cell regulatory network inference, and gene set enrichment analysis were performed to characterize the functional states of myeloid clusters. The spatial distribution of TAM subsets was determined in human glioma tissues using multiplex immunostaining. The prognostic value of different TAM-cluster specific gene sets was evaluated in the TCGA glioma cohort. Profiling and unbiased clustering of 24,227 myeloid cells from glioblastoma and Astro-IDH-mut-G4 identified nine myeloid cell clusters including monocytes, six Mo/Mg-TAM subsets, dendritic cells, and proliferative myeloid clusters. Different Mo/Mg-TAM clusters manifest functional and transcriptional diversity controlled by specific regulons. Multiplex immunostaining of subset-specific markers identified spatial enrichment of distinct TAM clusters at peri-vascular/necrotic areas in tumour parenchyma or at the tumour-brain interface. Glioblastoma harboured a substantially higher number of monocytes and Mo-TAM-inflammatory clusters, whereas Astro-IDH-mut-G4 had a higher proportion of TAM subsets mediating antigen presentation. Glioblastomas with a higher proportion of monocytes exhibited a mesenchymal signature, increased angiogenesis, and worse patient outcome. Our findings provide insight into myeloid cell diversity and its clinical relevance in IDH-differential grade 4 gliomas, and may serve as a resource for immunotherapy development. © 2022 The Pathological Society of Great Britain and Ireland.

Enhanced AMPAR-dependent synaptic transmission by S-nitrosylation in the vmPFC contributes to chronic inflammatory pain-induced persistent anxiety in mice.

Chronic pain patients often have anxiety disorders, and some of them suffer from anxiety even after analgesic administration. In this study, we investigated the role of AMPAR-mediated synaptic transmission in the ventromedial prefrontal cortex (vmPFC) in chronic pain-induced persistent anxiety in mice and explored potential drug targets. Chronic inflammatory pain was induced in mice by bilateral injection of complete Freund's adjuvant (CFA) into the planta of the hind paws; anxiety-like behaviours were assessed with behavioural tests; S-nitrosylation and AMPAR-mediated synaptic transmission were examined using biochemical assays and electrophysiological recordings, respectively. We found that CFA induced persistent upregulation of AMPAR membrane expression and function in the vmPFC of anxious mice but not in the vmPFC of non-anxious mice. The anxious mice exhibited higher S-nitrosylation of stargazin (an AMPAR-interacting protein) in the vmPFC. Inhibition of S-nitrosylation by bilaterally infusing an exogenous stargazin (C302S) mutant into the vmPFC rescued the surface expression of GluA1 and AMPAR-mediated synaptic transmission as well as the anxiety-like behaviours in CFA-injected mice, even after ibuprofen treatment. Moreover, administration of ZL006, a small molecular inhibitor disrupting the interaction of nNOS and PSD-95 (20 mg·kg-1·d-1, for 5 days, i.p.), significantly reduced nitric oxide production and S-nitrosylation of AMPAR-interacting proteins in the vmPFC, resulting in anxiolytic-like effects in anxious mice after ibuprofen treatment. We conclude that S-nitrosylation is necessary for AMPAR trafficking and function in the vmPFC under chronic inflammatory pain-induced persistent anxiety conditions, and nNOS-PSD-95 inhibitors could be potential anxiolytics specific for chronic inflammatory pain-induced persistent anxiety after analgesic treatment.

DPY30 Promotes Proliferation and Cell Cycle Progression of Colorectal Cancer Cells via Mediating H3K4 Trimethylation.

DPY30, a core subunit of the SET1/MLL histone H3K4 methyltransferase complexes, plays an important role in diverse biological functions through the epigenetic regulation of gene transcription, especially in cancer development. However, its involvement in human colorectal carcinoma (CRC) has not been elucidated yet. Here we demonstrated that DPY30 was overexpressed in CRC tissues, and significantly associated with pathological grading, tumor size, TNM stage, and tumor location. Furthermore, DPY30 knockdown remarkably suppressed the CRC cell proliferation through downregulation of PCNA and Ki67 in vitro and in vivo, simultaneously induced cell cycle arrest at S phase by downregulating Cyclin A2. In the mechanistic study, RNA-Seq analysis revealed that enriched gene ontology of cell proliferation and cell growth was significantly affected. And ChIP result indicated that DPY30 knockdown inhibited H3 lysine 4 trimethylation (H3K4me3) and attenuated interactions between H3K4me3 with PCNA, Ki67 and cyclin A2 respectively, which led to the decrease of H3K4me3 establishment on their promoter regions. Taken together, our results demonstrate overexpression of DPY30 promotes CRC cell proliferation and cell cycle progression by facilitating the transcription of PCNA, Ki67 and cyclin A2 via mediating H3K4me3. It suggests that DPY30 may serve as a potential therapeutic molecular target for CRC.

Kinetically and thermodynamically controlled one-pot growth of gold nanoshells with NIR-II absorption for multimodal imaging-guided photothermal therapy.

Since the successful clinical trial of AuroShell for photothermal therapy, there is currently intense interest in developing gold-based core-shell structures with near-infrared (NIR) absorption ranging from NIR-I (650-900 nm) to NIR-II (900-1700 nm). Here, we propose a seed-mediated successive growth approach to produce gold nanoshells on the surface of the nanoscale metal-organic framework (NMOF) of UiO-66-NH2 (UiO = the University of Oslo) in one pot. The key to this strategy is to modulate the proportion of the formaldehyde (reductant) and its regulator / oxidative product of formic acid to harness the particle nucleation and growth rate within the same system. The gold nanoshells propagate through a well-oriented and controllable diffusion growth pattern (points → facets → octahedron), which has not been identified. Most strikingly, the gold nanoshells prepared hereby exhibit an exceedingly broad and strong absorption in NIR-II with a peak beyond 1300 nm and outstanding photothermal conversion efficiency of 74.0%. Owing to such superior performance, these gold nanoshells show promising outcomes in photoacoustic (PA), computed tomography (CT), and photothermal imaging-guided photothermal therapy (PTT) for breast cancer, as demonstrated both in vitro and in vivo.

Possible sarcopenia and risk of new-onset type 2 diabetes mellitus in older adults in China: a 7-year longitudinal cohort study.

BACKGROUND: Previous studies have shown that type 2 diabetes mellitus (T2DM) can cause sarcopenia; however, these conditions may have a bidirectional association. This study aimed to explore the longitudinal association between possible sarcopenia and new-onset T2DM. METHODS: We conducted a population-based cohort study using nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS). This study included participants aged ≥ 60 years who were free of diabetes during the baseline survey of CHARLS (2011 to 2012) and were followed up until 2018. Possible sarcopenia status was defined according to the Asian Working Group for Sarcopenia 2019 criteria. Cox proportional hazards regression models were used to evaluate the effect of possible sarcopenia on new-onset T2DM. RESULTS: In total, 3,707 individuals were enrolled in this study, with a median age of 66 years; the prevalence of possible sarcopenia was 45.1%. During the 7-year follow-up, 575 cases (15.5%) of incident diabetes were identified. Participants with possible sarcopenia were more likely to have new-onset T2DM than those without possible sarcopenia (hazard ratio: 1.27, 95% confidence interval: 1.07-1.50; p = 0.006). In subgroup analysis, we found a significant association between possible sarcopenia and T2DM in individuals aged < 75 years or with a BMI < 24 kg/m². However, this association was not significant in individuals aged ≥ 75 years or with a BMI ≥ 24 kg/m². CONCLUSIONS: Possible sarcopenia is associated with an increased risk of new-onset T2DM in older adults, especially in individuals who are not overweight and aged 75 years or younger.

Behavioral trigger factors for hemorrhagic stroke: a case-crossover study.

BACKGROUND: The role and extent of the effects of short-term behavioral factors on the risk of hemorrhagic stroke (HS) are unclear. This study aimed to assess and quantify behavioral trigger factors (BTFs) for HS and identify the differences in BTFs between Chinese and other populations. METHODS: A case-crossover study was performed from March 2021 to February 2022. New-onset HS patients were recruited from two university hospitals in China. The patients were interviewed to evaluate their exposure to 20 potential BTFs during the predefined risk and control periods and to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). A comprehensive literature review was conducted to synthesize the evidence. RESULTS: A total of 284 patients with HS were included (150 with intracerebral hemorrhage and 134 with subarachnoid hemorrhage). Multivariate regression analysis showed that straining for defecation (OR: 3.06; 95% CI: 1.01-8.40), weightlifting (OR: 4.82; 95% CI: 1.02-22.83), overeating (OR: 4.33; 95% CI: 1.24-15.21), heavy physical exertion (OR: 3.02; 95% CI: 1.18-7.78), and chess/cards/mahjong games (OR: 2.51; 95% CI: 1.05-6.01) were associated with an increased risk within 2 hours before HS onset, and critical life events (OR: 3.81; 95% CI: 1.06-13.74) were associated with an increased risk 7 days before the onset of HS. Exposure to anger (OR: 3.17; 95% CI: 1.73-5.81) and heavy physical exertion (OR: 2.12; 95% CI: 1.65, 2.74) showed an increased risk of HS events after the pooled analysis. CONCLUSIONS: Several behavioral activities and mood modifications are associated with the onset of HS. In addition to the common BTFs, Chinese patients have specific BTFs due to their habits and customs distinct from those of different populations in other regions. Key messages What is already known on this topic It is known that several behavioral trigger factors (BTFs) are associated with the onset of hemorrhagic stroke (HS), such as vigorous physical exercise and anger. Evidence for other potential trigger factors was of less robustness. Which BTFs contribute to HS among the Chinese population is poorly understood, since individuals in different countries and regions have their own habits of life and customs. What this study adds Our study identified that two special behaviors, chess/card/mahjong games and critical life events, were associated with the onset of HS in Chinese populations, besides heavy physical exertion, weightlifting, overeating, and straining for defecation, which were previously reported in other populations. Heavy physical exertion and anger could potentially increase the risk of HS based on a comprehensive aggregation and evidence synthesis. How this study might affect research, practice, or policy Patients in different populations or regions may possess specific BTFs owing to their distinct habits and customs. Avoidance of these behaviors and regulation of emotions to maintain a steady mentality would help minimize exposure and prevent the disease for high-risk populations in China.

Short-term environmental triggers of hemorrhagic stroke.

Hemorrhagic stroke (HS) is associated with severe morbidity and high mortality. Identifying the trigger factors for HS is critical for disease prevention. This study aimed to assess the associations between short-term environmental triggers (STETs) and HS risk. We systematically searched six databases for articles published up to September 9, 2022. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using random-effect models to evaluate the associations between STETs and the risk of HS. Heterogeneity was assessed using Cochran Q and I2 tests. A total of 63 studies were included for analysis. Of these, 40 focused on air pollutants and 23 on meteorological factors. Pooling results showed that exposure to particulate matter 2.5 (PM2.5; OR, 1.003 per 10 µg/m3; 95% CI, 1.001-1.007), sulfur dioxide (SO2; OR, 1.022 per 10 ppb; 95% CI, 1.005-1.040), and nitrogen dioxide (NO2; OR, 1.026 per 10 ppb; 95% CI, 1.004-1.047) was associated with an increase in HS risk. Moreover, exposure to PM2.5 (OR, 1.018 per 10 µg/m3; 95% CI, 1.009-1.027) and SO2 (OR, 1.102 per 10 ppb; 95% CI, 1.010-1.204) was positively associated with the risk of intracerebral hemorrhage. In addition, extreme temperature, high pressures, high and low relative humidity were potentially associated with HS risk. Targeted preventive measures to limit the effect of these air pollutants and extreme meteorological factors should be taken to reduce the HS disease burden. Further studies are warranted to verify these findings.

[Effects of Qilan Prescription on the proliferation and apoptosis of human prostate cancer DU145 cells and its action mechanism].

OBJECTIVE: To investigate the effects of different concentrations of Qilan Prescription (QLP) on the proliferation and apoptosis of human PCa DU145 cells and its underlying mechanism. METHODS: We treated human PCa DU145 cells with QLP at 400, 200, 100, 50, 25, 12.5, 6.25, 3.125 or 1.56 µg/ml for 24, 48 and 72 hours respectively. Then we observed the morphological changes of the cells, examined their viability by CCK-8 assay, detected their cell cycle and apoptosis by flow cytometry, and determined the protein expressions of cyclin D1, Bax, Bcl-2 and cleaved-caspase 3 in the DU145 cells by Western blot, followed by comparison of the parameters with those obtained from the blank control group. RESULTS: QLP significantly inhibited the growth, reduced the contour clarity and adhesion ability of the DU145 cells at the concentrations of 100, 200 and 400 µg/ml, and markedly decreased the activity of the cells at 200 and 400 µg/ml, most significantly at 400 µg/ml. The number of the G2-phase DU145 cells was dramatically increased in all the concentration groups (P < 0.01), so was the total number of apoptotic DU145 cells (P < 0.01), while that of the S-phase cells remarkably decreased in the 400 µg/ml QLP (P < 0.01) and 200 µg/ml QLP (P < 0.05) groups. The expression of the cyclin D1 protein was significantly down-regulated in the 400 µg/ml QLP group (P < 0.01). That of Bcl-2 was also down-regulated (P < 0.01) while those of Bax and cleaved-caspase 3 up-regulated in the 400 and 200 µg/ml QLP groups (P < 0.01). CONCLUSION: QLP can inhibit the proliferation and promote the apoptosis of human PCa DU145 cells, which may be associated with its effects of down-regulating the expression of the cell cycle-related protein cyclin D1, disrupting the Bax-Bcl-2 balance, and up-regulating the expression of cleaved-caspase 3.