Palmitoylation of SARS-CoV-2 Envelope protein is central to virus particle formation.

The Envelope (E) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an integral structural protein in the virus particles. However, its role in the assembly of virions and the underlying molecular mechanisms are yet to be elucidated, including whether the function of E protein is regulated by post-translational modifications. In the present study, we report that SARS-CoV-2 E protein is palmitoylated at C40, C43, and C44 by palmitoyltransferases zDHHC3, 6, 12, 15, and 20. Mutating these three cysteines to serines (C40/43/44S) reduced the stability of E protein, decreased the interaction of E with structural proteins Spike, Membrane, and Nucleocapsid, and thereby inhibited the production of virus-like particles (VLPs) and VLP-mediated luciferase transcriptional delivery. Specifically, the C40/43/44S mutation of E protein reduced the density of VLPs. Collectively, these results demonstrate that palmitoylation of E protein is vital for its function in the assembly of SARS-CoV-2 particles.IMPORTANCEIn this study, we systematically examined the biochemistry of palmitoylation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) E protein and demonstrated that palmitoylation of SARS-CoV-2 E protein is required for virus-like particle (VLP) production and maintaining normal particle density. These results suggest that palmitoylated E protein is central for proper morphogenesis of SARS-CoV-2 VLPs in densities required for viral infectivity. This study presents a significant advancement in the understanding of how palmitoylation of viral proteins is vital for assembling SARS-CoV-2 particles and supports that palmitoyl acyltransferases can be potential therapeutic targets for the development of SARS-CoV-2 inhibitors.

Metabolic dysfunction-associated fatty liver disease and osteoporosis: the mechanisms and roles of adiposity.

Nonalcoholic fatty liver disease (NAFLD) has recently been renamed metabolic dysfunction-associated fatty liver disease (MAFLD) by international consensus. Both MAFLD and osteoporosis are highly prevalent metabolic diseases. Recent evidence indicates that NAFLD increases the risk of low bone mineral density and osteoporosis, likely mediated by obesity. NAFLD has a close association with obesity and other metabolic disorders. Although obesity was previously thought to protect against bone loss, it now heightens osteoporotic fracture risk. This overview summarizes current clinical correlations between obesity, NAFLD, and osteoporosis, with a focus on recent insights into potential mechanisms interconnecting these three conditions. This study reviewed the scientific literature on the relationship between obesity, nonalcoholic fatty liver disease, and osteoporosis as well as the scientific literature that reveals the underlying pathophysiologic mechanisms between the three. Emerging evidence suggests obesity plays a key role in mediating the relationship between NAFLD and osteoporosis. Accumulating laboratory evidence supports plausible pathophysiological links between obesity, NAFLD, and osteoporosis, including inflammatory pathways, insulin resistance, gut microbiota dysbiosis, bone marrow adiposity, and alterations in insulin-like growth factor-1 signaling. Adiposity has important associations with NAFLD and osteoporosis, the underlying pathophysiologic mechanisms between the three may provide new therapeutic targets for this complex patient population.

Cleavage of Stau2 by 3C protease promotes EV-A71 replication.

BACKGROUND: Enterovirus A71 (EV-A71), as a neurotropic virus, mainly affects infants and young children under the age of 5. EV-A71 infection causes hand-foot-mouth disease and herpetic angina, and even life-threatening neurological complications. However, the molecular mechanism by which EV-A71 induces nervous system damage remains elusive. The viral protease 3C plays an important role during EV-A71 infection and is also a key intersection of virus-host interactions. Previously, we used yeast two-hybrid to screen out the host protein Double-stranded RNA-binding protein Staufen homolog 2 (Stau2), an important member involved in neuronal mRNA transport, potentially interacts with 3C. METHODS: We used coimmunoprecipitation (Co-IP) and immunofluorescence assay (IFA) to confirm that EV-A71 3C interacts with Stau2. By constructing the mutant of Stau2, we found the specific site where the 3C protease cleaves Stau2. Detection of VP1 protein using Western blotting characterized EV-A71 viral replication, and overexpression or knockdown of Stau2 exhibited effects on EV-A71 replication. The effect of different cleavage products on EV-A71 replication was demonstrated by constructing Stau2 truncates. RESULTS: In this study, we found that EV-A71 3C interacts with Stau2. Stau2 is cleaved by 3C at the Q507-G508 site. Overexpression of Stau2 promotes EV-A71 VP1 protein expression, whereas depletion of Stau2 by small interfering RNA inhibits EV-A71 replication. Stau2 is essential for EV-A71 replication, and the product of Stau2 cleavage by 3C, 508-570 aa, has activity that promotes EV-A71 replication. In addition, we found that mouse Stau2 is also cleaved by EV-A71 3C at the same site. CONCLUSIONS: Our research provides an example for EV-A71-host interaction, enriching key targets of host factors that contribute to viral replication.

Spatiotemporal and Multilayer Trade Network Patterns of the Global Cobalt Cycle.

Recent years have witnessed increasing attempts to track trade flows of critical materials across world regions and along the life cycle for renewable energy and the low carbon transition. Previous studies often had limited spatiotemporal coverage, excluded end-use products, and modeled different life cycle stages as single-layer networks. Here, we integrated material flow analysis and complex network analysis into a multilayer framework to characterize the spatiotemporal and multilayer trade network patterns of the global cobalt cycle from 1988 to 2020. We found substantial growth and notable structural changes in global cobalt trade over the past 30 years. China, Germany, and the United States play pivotal roles in different layers and stages of the global cobalt cycle. The interlayer relationships among alloys, batteries, and materials are robust and continually strengthening, indicating a trend toward synergistic trade. However, cobalt ore-exporting countries are highly concentrated and rarely involved in later life cycle stages, resulting in the weakest relationship between the ore layer and other layers. This causes fluctuations and uncertainty in the global cobalt trade. Our model, linking industrial ecology, supply chain analysis, and network analysis, can be extended to other materials that are critical for the future green transition.

Metabolic syndrome, its components, and gastrointestinal cancer risk: a meta-analysis of 31 prospective cohorts and Mendelian randomization study.

BACKGROUND AND AIM: Cohort studies have linked metabolic syndrome (MetS) to gastrointestinal (GI) cancer risk. We aimed to evaluate the associations between MetS, its components, and combinations of MetS components with eight GI cancers risk. METHODS: We conducted a systematic search of prospective cohort studies and performed a meta-analysis. Subgroup analyses regarding diagnostic criteria, sex, cancer sites, histological subtypes, ethnic groups, and studies adjusted for alcohol consumption were carried out. Mendelian randomization (MR) was employed to evaluate the causality between 17 MetS-related traits and eight GI cancers among Europeans and Asians separately. RESULTS: Meta-analyses of 31 prospective studies indicated that MetS was significantly associated with an increased risk of colorectal cancer (CRC) (RR [95% CI] = 1.13 [1.12-1.15]), esophageal cancer (EC) (RR [95% CI] = 1.17 [1.03-1.32]), gallbladder cancer (GBC) (RR [95% CI] = 1.37[1.10-1.71]), liver cancer (LC) (RR [95% CI] = 1.46 [1.29-1.64]), and pancreatic cancer (PaC) (RR [95% CI] = 1.25 [1.20-1.30]), but not gastric cancer (GC) (RR [95% CI] = 1.11 [0.96-1.28]). Regarding the associations between MetS components and GI cancers risk, the following associations showed statistical significance: obesity-CRC/LC/EC/, hypertriglyceridemia-LC/PaC, reduced high-density lipoprotein (HDL)-CRC/LC/GC/PaC, hyperglycemia-CRC/LC/PaC, and hypertension-CRC/LC/EC/PaC. Sex-specific associations were observed between individual MetS components on GI cancers risk. Among the top three common combinations in both sexes, obesity + HTN + hyperglycemia had the strongest association with CRC risk (RR [95% CI] = 1.54 [1.49-1.61] for males and 1.27 [1.21-1.33] for females). MR analyses revealed causality in 16 exposure-outcome pairs: waist-to-hip ratio/BMI/HbA1c-CRC; BMI/childhood obesity/waist circumference/T2DM/glucose-EC; BMI/waist circumference/cholesterol-LC; cholesterol/childhood obesity/waist circumference/HbA1c-PaC; and HbA1c-GBC. These results were robust against sensitivity analyses. CONCLUSIONS: Since MetS is reversible, lifestyle changes or medical interventions targeting MetS patients might be potential prevention strategies for GI cancers.

Sunitinib alleviates hepatic ischemia reperfusion injury by inhibiting the JAK2/STAT pathway and promoting the M2 polarization of macrophages.

BACKGROUND: Hepatic ischemia reperfusion injury (IRI) is a common liver surgery complication. This study aims to explore the effect and potential mechanism of Sunitinib - a multi-target tyrosine kinase inhibitor - on hepatic IRI. METHODS: We established a hepatic IRI model using C57BL/6 mice, and integrated 40 mg/kg of Sunitinib, solely or combined with 100 µg/kg of coumermycin A1 (C-A1), in the treatment strategy. H&E staining, TUNEL assay, and detection of serum ALT and AST activities were used to assess liver damage. Further, ELISA kits and Western Blots were utilized to determine IL-1ß, TNF-α, IL-6, CXCL10, and CXCL2 levels. Primary macrophages, once isolated, were cultured in vitro with either 2 nM of Sunitinib, or Sunitinib in conjunction with 1 µM of C-A1, to gauge their influence on macrophage polarization. qPCR and Western blot were conducted to examine the level of p-STAT1/STAT1, p-STAT3/STAT3, p-JAK2/JAK2, and M1/M2 polarization markers. To quantify immune cell infiltration, we applied Immunofluorescence. RESULTS: Sunitinib pretreatment significantly alleviated liver injury and reduced p-STAT1/STAT1, p-STAT3/STAT3, p-JAK2/JAK2 levels. In vitro, Sunitinib treatment curbed M1 polarization induced by LPS + IFN-γ and bolstered M2 polarization triggered by IL-4. C-A1 application upregulated JAK2/STAT pathway phosphorylation and promoted LPS + IFN-γ-induced M1 polarization, which was reversed by Sunitinib treatment. In IL-4-stimulated macrophages, application of C-A1 activated the JAK2/STAT pathway and decreased M2-type macrophages, which was reversed by Sunitinib treatment either. CONCLUSION: Sunitinib is capable of guiding the polarization of macrophages toward an M2-type phenotype via the inhibition of the JAK2/STAT pathway, thereby exerting a protective effect on hepatic IRI.

A Smith Predictor Modified with a Pseudo Feedforward Control for the Charge-Coupled Device-Based Optoelectronic Tracking System.

In the high-precision optoelectronic tracking system (OTS) based on a charge-coupled device (CCD), the boresight error extracted from the tracking image contains an undeniable delay, which directly limits the control bandwidth of visual tracking. High bandwidth means high response speed and tracking accuracy. Generally, a model-based delay compensation control method called the Smith predictor is utilized to separate time delay from the closed loop to promote the control bandwidth. However, due to the existence of errors between the established model and the real object, the improvement in the bandwidth is still limited to ensure system stability, resulting in insufficient tracking performance. In this paper, to solve the problem, a Smith predictor modified with pseudo feedforward control for the OTS is proposed. The experimental results demonstrate that the proposed method achieves significant improvements in tracking performance, reducing the maximum residual error at 1 Hz from 365 arcseconds (using the classic Smith predictor) to 283 arcseconds, a 22.5% improvement. Across the main frequency band (0.2 Hz to 2 Hz), the residual errors were consistently lower using the proposed method.

Thriving at work as a mediator of the relationship between psychological resilience and the work performance of clinical nurses.

OBJECTIVE: This study aims to investigate the relationship between psychological resilience, thriving at work, and work performance among nurses, as well as analyse the mediating role of thriving at work in the relationship between psychological resilience and the work performance of nurses. The findings are intended to serve as a reference for nursing managers to design tailored work performance intervention programs. METHOD: Using convenience sampling, 308 clinical nurses were selected from a tertiary hospital in Changsha City, Hunan Province, China, from February to April 2023. The Connor-Davidson Resilience Scale (CD-RISC), the Thriving at Work Scale, and the Work Performance Scale were employed for the questionnaire survey. Pearson correlation analysis was used to explore the relationship between psychological resilience, thriving at work and work performance. The SPSS 26.0 software's 'Process' plugin was utilised for mediation effect analysis. RESULTS: Significantly positive correlations were found between psychological resilience and thriving at work (r = 0.806, P < 0.01), thriving at work and work performance (r = 0.571, P < 0.01) as well as psychological resilience and work performance (r = 0.572, P < 0.01). Psychological resilience significantly predicted work performance positively (ß = 0.558, t = 11.165, P < 0.01), and this prediction remained significant when thriving at work (the mediating variable), was introduced (ß = 0.371, t = 4.772, P < 0.01). Psychological resilience significantly predicted thriving at work positively (ß = 0.731, t = 20.779, P < 0.01), and thriving at work significantly predicted work performance positively (ß = 0.256, t = 3.105, P < 0.05). The mediating effect size of thriving at work between psychological resilience and work performance was 33.49% (P < 0.05). CONCLUSION: Thriving at work plays a partial mediating role between psychological resilience and work performance. The level of work performance among clinical nurses was relatively high. Nursing managers can enhance thriving at work by fostering psychological resilience among clinical nurses, thereby further improving their work performance to ensure high-quality and efficient nursing care.

Obesity induces male mice infertility via oxidative stress, apoptosis, and glycolysis.

In brief: The current declining trend in male fertility parallels the increasing prevalence of obesity worldwide. This paper revealed that the poor in vitro fertilization rates and decreased sperm motility in obese mice due to excessive oxidative stress enhanced apoptosis and impaired glucose metabolism in the testes. Abstract: Obesity is an urgent public health problem in recent decades, linked to reduced reproductive potential, and negatively affects the success of assisted reproduction technology. The aim of this study is to investigate the mechanisms underlying impaired male fertility caused by obesity. Male C57BL/6 mice fed a high-fat diet for 20 weeks served as mouse models with moderate (20% < body fat rate (BFR) < 30%) and severe obesity (BFR > 30%). Our results showed poor in vitro fertilization rates and decreased sperm motility in obese mice. Abnormal testicular structures were identified in male mice with moderate and severe obesity. The expression level of malondialdehyde increased with obesity severity. This finding indicates that oxidative stress plays a role in male infertility caused by obesity, which was further confirmed by the decreased expression of nuclear factor erythroid 2-related factor 2, superoxide dismutase, and glutathione peroxidases. Our study also found that the expression of cleaved caspase-3 and B-cell lymphoma-2 showed an obesity severity-dependent manner indicating that apoptosis is highly correlated with male infertility caused by obesity. Moreover, the expression of glycolysis-related proteins, including glucose transporter 8, lactate dehydrogenase A, monocarboxylate transporter 2 (MCT2), and MCT4, decreased significantly in the testes of obese male mice, suggesting energy supply for spermatogenesis is impaired by obesity. Taken together, our findings provide evidence that obesity impairs male fertility through oxidative stress, apoptosis, and blockage of energy supply in the testes and suggest that male obesity influences fertility through complex and multiple mechanisms.

PREB inhibits the replication of prototype foamy virus by affecting its transcription.

BACKGROUND: Foamy viruses (FVs) are unique nonpathogenic retroviruses, which remain latent in the host for a long time. Therefore, they may be safe, effective gene transfer vectors. In this study, were assessed FV-host cell interactions and the molecular mechanisms underlying FV latent infection. METHODS: We used the prototype FV (PFV) to infect HT1080 cells and a PFV indicator cell line (PFVL) to measure virus titers. After 48 h of infection, the culture supernatant (i.e., cell-free PFV particles) and transfected cells (i.e., cell-associated PFV particles) were harvested and incubated with PFVL. After another 48 h, the luciferase activity was used to measure virus titers. RESULTS: Through transcriptomics sequencing, we found that PREB mRNA expression was significantly upregulated. Moreover, PREB overexpression reduced PFV replication, whereas endogenous PREB knockdown increased PFV replication. PREB interacted with the Tas DNA-binding and transcriptional activation domains and interfered with its binding to the PFV long terminal repeat and internal promoter, preventing the recruitment of transcription factors and thereby inhibiting the transactivation function of Tas. PREB C-terminal 329-418 aa played a major role in inhibiting PFV replication; PREB also inhibited bovine FV replication. Therefore, PREB has a broad-spectrum inhibitory effect on FV replication. CONCLUSIONS: Our results demonstrated that PREB inhibits PFV replication by impeding its transcription.

CircACTR2 in macrophages promotes renal fibrosis by activating macrophage inflammation and epithelial-mesenchymal transition of renal tubular epithelial cells.

The crosstalk between macrophages and tubular epithelial cells (TECs) actively regulates the progression of renal fibrosis. In the present study, we revealed the significance of circular RNA ACTR2 (circACTR2) in regulating macrophage inflammation, epithelial-mesenchymal transition (EMT) of TECs, and the development of renal fibrosis. Our results showed UUO-induced renal fibrosis was associated with increased inflammation and EMT, hypertrophy of contralateral kidney, up-regulations of circACTR2 and NLRP3, and the down-regulation of miR-561. CircACTR2 sufficiently and essentially promoted the activation of NLRP3 inflammasome, pyroptosis, and inflammation in macrophages, and through paracrine effect, stimulated EMT and fibrosis of TECs. Mechanistically, circACTR2 sponged miR-561 and up-regulated NLRP3 expression level to induce the secretion of IL-1ß. In TECs, IL-1ß induced renal fibrosis via up-regulating fascin-1. Knocking down circACTR2 or elevating miR-561 potently alleviated renal fibrosis in vivo. In summary, circACTR2, by sponging miR-561, activated NLRP3 inflammasome, promoted macrophage inflammation, and stimulated macrophage-induced EMT and fibrosis of TECs. Knocking down circACTR2 and overexpressing miR-561 may, thus, benefit the treatment of renal fibrosis.

[Genetic analysis of a fetus with mosaic trisomy 12 and severe heart defects and a literature review].

OBJECTIVE: To explore the genetic basis for a fetus with severe heart defect and mosaic trisomy 12, and the correlation between chromosomal abnormalities and clinical manifestations and pregnancy outcome. METHODS: A 33-year-old pregnant woman who presented at Lianyungang Maternal and Child Health Care Hospital on May 17, 2021 due to abnormal fetal heart development revealed by ultrasonography was selected as the study subject. Clinical data of the fetus were collected. Amniotic fluid sample of the pregnant women was collected and subjected to G-banded chromosomal karyotyping and chromosomal microarray analysis (CMA). The CNKI, WanFang and PubMed databases were searched with key words, with the retrieval period set as from June 1, 1992 to June 1, 2022. RESULTS: For the 33-year-old pregnant woman, ultrasonography at 22+6 gestational weeks had revealed abnormal fetal heart development and ectopic pulmonary vein drainage. G-banded karyotyping showed that the fetus has a karyotype of mos 47,XX,+12[1]/46,XX[73], with the mosaicism rate being 1.35%. CMA results suggested that about 18% of fetal chromosome 12 was trisomic. A newborn was delivered at 39 weeks of gestation. Follow-up confirmed severe congenital heart disease, small head circumference, low-set ears and auricular deformity. The infant had died 3 months later. The database search has retrieved 9 reports. Literature review suggested that the liveborn infants with mosaic trisomy 12 had diverse clinical manifestations depending on the affected organs, which had included congenital heart disease and/or other organs and facial dysmorphisms, resulting in adverse pregnancy outcomes. CONCLUSION: Trisomy 12 mosaicism is an important factor for severe heart defects. The results of ultrasound examination have important value for evaluating the prognosis of the affected fetuses.

Impacts of abandoned sloping farmland on soil aggregates and aggregate-associated organic carbon in karst rocky desertification areas.

Vegetation restoration after the abandonment of sloping farmland can effectively promote the sequestration of soil organic carbon (SOC), with soil aggregates playing a pivotal role. However, in abandoned farmlands in karst regions with varying degrees of rocky desertification, the relationship between soil aggregates, aggregate-associated organic carbon (AAOC), and total SOC content remains unclear. Taking abandoned sloping farmlands (5 years, 10 years, and 15 years) with different levels of rocky desertification (no rocky desertification, potential rocky desertification, slight rocky desertification, and moderate rocky desertification) in a typical karst area as research objects, this study investigated the dynamic characteristics of the particle size distribution of soil aggregates, total SOC, and AAOC. The results indicated that total SOC content in the 0-20 cm soil layer increased after abandonment in all levels of rocky desertification, peaking after 15 years. The abandoned sloping farmland with moderate desertification showed the best recovery effect. Post-abandonment vegetation restoration increased the content of 5-10 mm soil aggregates, but decreased those of 1-2 mm and < 0.25 mm aggregates. Particularly for 5-10 mm aggregates, the contribution of AAOC to total SOC significantly increased over time. Moreover, a strong correlation was observed between >1 mm aggregates and total SOC (p < 0.05). The increase in total SOC was primarily driven by the growth of AAOC in 5-10 mm aggregates. In general, vegetation restoration is an effective approach for enhancing total SOC content in abandoned sloping farmland with varying degrees of rocky desertification.

Glyphosate spraying exacerbates nitrogen and phosphorus loss in karst slope farmland.

Glyphosate herbicide is an indispensable material in agricultural production. In order to explore the potential environmental effects of glyphosate application in karst slope farmland, this paper used a variable slope steel tank to simulate the surface microtopography and underground pore structure characteristics of karst slope farmland, and combined with artificial rainfall experiments to explore the migration path of glyphosate in karst slope farmland and the impact of spraying glyphosate on soil nitrogen and phosphorus loss. The results showed that under the condition of heavy rain, glyphosate in karst slope farmland was mainly transported and diffused by surface runoff, supplemented by underground runoff; secondly, in different hydrological paths, glyphosate directly affected the content of nitrogen and phosphorus in runoff, and all showed extremely significant positive correlation (p < 0.001). In addition, rainfall conditions such as rainfall intensity, rainfall duration, and runoff affected the content of nitrogen and phosphorus in runoff to varying degrees. In conclusion, the application of glyphosate significantly increased the content of nitrogen and phosphorus in different runoff and accelerated the loss of nitrogen and phosphorus from soil, which not only led to soil degradation, but also threatened the safety of aquatic ecosystem. Therefore, in the prevention and control of agricultural non-point source pollution, the threat of glyphosate to the surrounding aquatic ecosystem cannot be ignored, especially in karst areas with frequent rainstorms and serious water erosion, long-term monitoring and risk assessment of glyphosate are needed.

Antiviral role of IFITM3 in prototype foamy virus infection.

BACKGROUND: Foamy viruses (FVs) are retroviruses with unique replication strategies that cause lifelong latent infections in their hosts. FVs can also produce foam-like cytopathic effects in vitro. However, the effect of host cytokines on FV replication requires further investigation. Although interferon induced transmembrane (IFITMs) proteins have become the focus of antiviral immune response research due to their broad-spectrum antiviral ability, it remains unclear whether IFITMs can affect FV replication. METHOD: In this study, the PFV virus titer was characterized by measuring luciferase activity after co-incubation of PFVL cell lines with the cell culture supernatants (cell-free PFV) or the cells transfected with pcPFV plasmid/infected with PFV (cell-associated PFV). The foam-like cytopathic effects of PFV infected cells was observed to reflect the virus replication. The total RNA of PFV infected cells was extracted, and the viral genome was quantified by Quantitative reverse transcription PCR to detect the PFV entry into target cells. RESULTS: In the present study, we demonstrated that IFITM1-3 overexpression inhibited prototype foamy virus (PFV) replication. In addition, an IFITM3 knockdown by small interfering RNA increased PFV replication. We further demonstrated that IFITM3 inhibited PFV entry into host cells. Moreover, IFITM3 also reduced the number of PFV envelope proteins, which was related to IFITM3 promoted envelope degradation through the lysosomal pathway. CONCLUSIONS: Taken together, these results demonstrate that IFITM3 inhibits PFV replication by inhibiting PFV entry into target cells and reducing the number of PFV envelope.

In Situ Crumpling of Gold Nanosheets into Spherical Three-Dimensional Architecture: Probing the Aggregation-Induced Enhancement in Photothermal Properties.

Assembling two-dimensional noble metal nanocrystals into a three-dimensional mesoporous structure is of great value to solve the re-stacking issue for the practical application, which still remains a challenging technique. Herein, we report the one-pot fabrication of gold (Au) nanostructures with a crumpled paper ball-like morphology (Au NCPBs). The success of current work relies on the use of glutathione to crumple the branched Au nanosheets formed during the early stage, into spherical three-dimensional architecture, where the nanosheets are assembled with a mesoporous structure without intimate contact. When working as the agent toward photothermal conversion, the Au NCPBs exhibit enhanced photothermal conversion efficiency (η = 19.9%), as compared to that of flat and wrinkled Au nanosheets. Such an enhancement should be owing to the aggregation-induced effect, where the shortened inter-sheet distance contributes to an increased coupling between the plasmon oscillations/fields of the interacting Au nanosheets. The present study offers a feasible strategy to create spherical architecture of crumpled Au nanosheets and validates their structural advantage in photothermal applications, which could be potentially extended to other metals or alloys.

Calcyphosine promotes the proliferation of glioma cells and serves as a potential therapeutic target.

Calcyphosine (CAPS) was initially identified from the canine thyroid. It also exists in many types of tumor, but its expression and function in glioma remain unknown. Here we explored the clinical significance and the functional mechanisms of CAPS in glioma. We found that CAPS was highly expressed in glioma and high expression of CAPS was correlated with poor survival, in glioma patients and public databases. Cox regression analysis showed that CAPS was an independent prognostic factor for glioma patients. Knockdown of CAPS suppressed the proliferation, whereas overexpression of CAPS promoted the proliferation of glioma both in vitro and in vivo. CAPS regulated the G2/M phase transition of the cell cycle, but had no obvious effect on apoptosis. CAPS affected PLK1 phosphorylation through interaction with MYPT1. CAPS knockdown decreased p-MYPT1 at S507 and p-PLK1 at S210. Expression of MYPT1 S507 phosphomimic rescued PLK1 phosphorylation and the phenotype caused by CAPS knockdown. The PLK1 inhibitor volasertib enhanced the therapeutic effect of temozolomide in glioma. Our data suggest that CAPS promotes the proliferation of glioma by regulating the cell cycle and the PLK1 inhibitor volasertib might be a chemosensitizer of glioma. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Safety and efficacy of pharmacotherapy containing INSTIs and chemotherapy drugs in people living with HIV and concomitant colorectal cancer.

BACKGROUND: Previous clinical data have shown that raltegravir-based antiretroviral therapy (ART) with fewer drug-drug interactions (DDIs) and adverse events (AEs) is a good regimen in patients with HIV infection who need cancer chemotherapy. There are currently few data on ART regimens that include Integrase inhibitors (INSTIs) other than RAL among this patient subgroup. METHODS: We evaluated the safety and efficacy of different kinds of INSTI-based regimens among patients with HIV and concomitant colorectal cancer (CRC) who received antineoplastic agents. RESULTS: From January 2020 to November 2021, 66 patients were enrolled. The patients were divided into three groups: 20 patients treated with dolutegravir (DTG)/lamivudine (3TC)/tenofovir (TDF) (group I), 24 patients treated with DTG/albuvirtide (ABT) (group II), and 22 patients treated with bictegravir (BIC)/tenofovir alafenamide (TAF)/emtricitabine (FTC) (group III). The majority of AEs during treatment were of grade 1-2. Treatment-related AEs of grade 3-4 occurred in 6 patients (9.09%), and no grade 5 AEs occurred. The most common AEs were nausea (100%) and neutrophils (84.85%) attributed to anticancer agents, and there was no significant difference in the incidence of these AEs among the three groups (P > 0.05). Viral load rebound was not observed among pretreated patients during chemotherapy. The viral load of untreated patients who started their ART concomitant with chemotherapy almost decreased to the lower limit of detection 6 months after ART initiation (only one patient in group III had a viral load of 102 copies/ml). At the 6th month, the CD4 count in group I decreased significantly from baseline (P < 0.05). However, the change in CD4 count was not significant in group II (P = 0.457) or group III (P = 0.748). CONCLUSIONS: DTG- or BIC-containing regimens are good options for patients with HIV and concomitant CRC.

Negatively Charged Sulfur Quantum Dots for Treatment of Drug-Resistant Pathogenic Bacterial Infections.

Drug-resistant pathogenic bacteria as a worldwide health threat calls for valid antimicrobial agents and tactics in clinical practice. Positively charged materials usually achieve antibacteria through binding and disrupting bacterial membranes via electrostatic interaction, however, they also usually cause hemolysis and cytotoxicity. Herein, we engineered negatively charged sulfur quantum dots (SQDs) as an efficient broad-spectrum antibiotic to kill drug-resistant bacteria in vitro and in vivo. The SQDs can destroy the bacterial membrane system and affect their metabolism due to the intrinsic antibacterial activity of elemental sulfur and catalytic generation of reactive oxygen species, which exhibit effective therapeutic effect on subcutaneously implanted infection model induced by representative pathogenic Methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. Plus, the negatively charged surface makes the SQDs have excellent hemocompatibility and low toxicity, which all highlight the critical prospect of the SQDs as a potent biocompatible antibacterial agent in clinical infection therapy.

Changes in RT-PCR test results and symptoms during the menstrual cycle of female individuals infected with SARS-CoV-2: Report of two cases.

The implications of the menstrual cycle for disease susceptibility, development, and severity of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are largely unknown. Here, we describe two women infected with SARS-CoV-2 whose real-time reverse transcriptase-polymerase chain reaction (RT-PCR) test results and symptoms changed during the menstrual cycle. The first patient developed a fever on the first day of her menstrual period, and again on the first day of her next menstrual period after hospital discharge. RT-PCR test results were positive during the first menstrual period before admission, but turned negative during hospitalization, and then were positive again during the second menstrual period after hospital discharge. Another one also developed a fever again on the first day of her menstrual period after hospital discharge. RT-PCR test results were negative before admission and during hospitalization, but turned positive during the first menstrual period after hospital discharge. The cases indicate sex hormones may play an important role in SARS-CoV-2 infection. For women with history of exposure to SARS-CoV-2, the management protocol should include assessment of the menstrual status.