Efficacy of Voluntary Medical Male Circumcision to Prevent HIV Infection Among Men Who Have Sex With Men : A Randomized Controlled Trial.

BACKGROUND: Observational studies suggest that voluntary medical male circumcision (VMMC) may lower HIV risk among men who have sex with men (MSM). A randomized controlled trial (RCT) is needed to confirm this. OBJECTIVE: To assess the efficacy of VMMC in preventing incident HIV infection among MSM. DESIGN: An RCT with up to 12 months of follow-up. (Chinese Clinical Trial Registry: ChiCTR2000039436). SETTING: 8 cities in China. PARTICIPANTS: Uncircumcised, HIV-seronegative men aged 18 to 49 years who self-reported predominantly practicing insertive anal intercourse and had 2 or more male sex partners in the past 6 months. INTERVENTION: VMMC. MEASUREMENTS: Rapid testing for HIV was done at baseline and at 3, 6, 9, and 12 months. Behavioral questionnaires and other tests for sexually transmitted infections were done at baseline, 6 months, and 12 months. The primary outcome was HIV seroconversion using an intention-to-treat analysis. RESULTS: The study enrolled 124 men in the intervention group and 123 in the control group, who contributed 120.7 and 123.1 person-years of observation, respectively. There were 0 seroconversions in the intervention group (0 infections [95% CI, 0.0 to 3.1 infections] per 100 person-years) and 5 seroconversions in the control group (4.1 infections [CI, 1.3 to 9.5 infections] per 100 person-years). The HIV hazard ratio was 0.09 (CI, 0.00 to 0.81; P = 0.029), and the HIV incidence was lower in the intervention group (log-rank P = 0.025). The incidence rates of syphilis, herpes simplex virus type 2, and penile human papillomavirus were not statistically significantly different between the 2 groups. There was no evidence of HIV risk compensation. LIMITATION: Few HIV seroconversions and limited follow-up period. CONCLUSION: Among MSM who predominantly practice insertive anal intercourse, VMMC is efficacious in preventing incident HIV infection; MSM should be included in VMMC guidelines. PRIMARY FUNDING SOURCE: The National Science and Technology Major Project of China.

Enhancement of root sulfur metabolic pathway by overexpression of OAS-TL3 to increase total soybean seed protein content.

Sulfur is essential for plant growth, and the uptake of sulfate by plant roots is the primary source of plant sulfur. Previous studies have shown that the OAS-TL gene is a key enzyme in the sulfur metabolic pathway and regulates cysteine (Cys) synthase production. However, the interaction mechanism of the glycine max OAS-TL3 Cys synthase (OAS-TL3) gene on soybean root morphology construction and seed protein accumulation is unclear. This study shows that mutant M18 has better root growth and development, higher seed protein content, and higher methionine (Met) content in sulfur-containing amino acids than wild-type JN18. By transcriptome sequencing, the differentially expressed OAS-TL3 gene was targeted in the mutant M18 root line. The relative expression of the OAS-TL3 gene in roots, stems, and leaves during the seedling, flowering, and bulking stages of the OAS-TL3 gene overexpression lines is higher than that of the recipient material. Compared to the recipient material JN74, the enzymatic activities, Cys, and GSH contents of OAS-TL are higher in the sulfur metabolic pathway of seedling roots. The receptor material JN74 is exogenously applied with different concentrations of reduced glutathione. The results demonstrate a positive correlation between reduced glutathione on total root length, projected area, surface area, root volume, total root tip number, total bifurcation number, and total crossing number. The Met and total protein contents of sulfur-containing amino acids in soybean seeds of the OAS-TL3 gene overexpression lines are higher than those of the recipient material JN74, while the gene-edited lines show the opposite results. In conclusion, the OAS-TL3 gene positively regulates soybean root growth, root activity, and the content of Met in the seeds through the OAS-TL-Cys-GSH pathway. It breaks the limitation of other amino acids and facilitates the increase of total seed protein content. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-022-01348-y.

[Research progress on chemical constituents and pharmacological effects of Glechomae Herba and prediction of its Q-markers].

Glechomae Herba, the dried aerial part of Glechoma longituba(Labiatae), has the effects of promoting urination, draining dampness, and relieving stranguria. It has received wide attention in recent years owing to the satisfactory efficacy on lithiasis. Amid the in-depth chemical and pharmacological research, it has been found that Glechomae Herba has antibacterial, anti-inflammatory, antioxidant, antithrombotic, hepatoprotective, cholagogic, antitumor, hypoglycemic, and lipid-lowering effects. The main chemical constituents are volatile oils, flavonoids, terpenoids, phenylpropanoids, and organic acids. This paper summarized the chemical constituents and pharmacological effects of Glechomae Herba. Based on genetic relationship of plants, the characteristics, efficacy, and pharmacokinetics of the chemical constituents, and the potential of these constituents as quality markers(Q-markers), it was summed up that ursolic acid, caffeic acid, rosmarinic acid, luteolin-7-O-diglucuronide, apigenin, apigenin-7-O-diglucuronide, apigetrin, and glechone can be the candidate Q-markers of Glechomae Herba.

Voluntary Medical Male Circumcision and Incident HIV Infection Among Men Who Have Sex With Men in China (The CoM Study): Protocol for a Randomized Controlled Trial.

BACKGROUND: Systematic reviews and meta-analyses based on observational studies have shown voluntary medical male circumcision (VMMC) may reduce HIV risk among men who have sex with men (MSM). There is a lack of randomized controlled trial (RCT) data assessing the efficacy of VMMC. OBJECTIVE: The primary objective of this study was to assess the efficacy of VMMC for preventing HIV acquisition among MSM who primarily engage in insertive anal sex. METHODS: A multicenter RCT will be conducted among MSM in 8 cities in China. Eligible participants are men aged 18-49 years who self-report ≥2 male sex partners in the past 6 months, predominantly practice insertive anal sex, and are willing to undergo circumcision. Interested men who satisfy inclusion criteria will be tested for HIV 1 month before enrollment and at enrollment, and only those who are HIV negative will be enrolled. At baseline, all enrolled participants will be asked to report sociodemographic characteristics and sexual behaviors; provide a blood sample for HIV, syphilis, and herpes simplex virus type 2 testing; and provide a penile swab for human papillomavirus testing. Participants will be randomly assigned to the intervention or control group. Those in the intervention group will receive VMMC and undergo a web-based weekly follow-up assessment of postsurgery healing for 6 consecutive weeks. All participants will be tested for HIV at 3-, 6-, 9-, and 12-month follow-ups. All participants will also be asked to report sexual behaviors and undergo repeat herpes simplex virus type 2 and human papillomavirus testing at 6- and 12-month follow-ups. The primary end point is HIV seroconversion. Secondary end points are the safety and satisfaction with VMMC and the changes in sexual behaviors after VMMC. The grouped censored data will be analyzed by intention-to-treat approach. RESULTS: Recruitment for the RCT began in August 2020 and continued through July 2022. Data collection is expected to be completed by July 2023, and full data analysis is going to be completed by September 2023. CONCLUSIONS: This study will be the first RCT to assess the efficacy of VMMC in preventing HIV infection among MSM. Results from this trial will provide preliminary evidence for the potential efficacy of VMMC to reduce incident HIV infection among MSM. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000039436; https://www.chictr.org.cn/showproj.html?proj=63369. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/47160.

Development of a flat conical chamber-based non-dispersive infrared CO2 gas sensor with temperature compensation.

In order to accurately monitor CO2 concentration based on the non-dispersive infrared technique, a novel flat conical chamber CO2 gas sensor is proposed and investigated by simulation analysis and experimental verification. First, the optical design software and computational fluid dynamics method are utilized to theoretically investigate the relationship between the energy distribution, absorption efficiency of infrared radiation, and chamber size. The simulation results show that the chamber length has an optimal value of 8 cm when the cone angle is 5° and the diameter of the detection surface is 1 cm, which makes infrared absorption efficiency optimal. Then, the flat conical chamber CO2 gas sensor system is developed, calibrated, and tested. The experimental results indicate that the sensor can accurately detect CO2 gas concentrations in the range of 0-2000 ppm at 25 °C. It is found that the absolute error of calibration is within 10 ppm, and the maximum repeatability and stability errors are 5.5 and 3.5%, respectively. Finally, the genetic neural network algorithm is presented to compensate for the output concentration of the sensor to solve the problem of temperature drift. Experimental results demonstrate that the relative error of the compensated CO2 concentration is varied from -0.85 to 2.32%, which is significantly reduced. The study has reference significance for the structural optimization of the infrared CO2 gas sensor and the improvement of the measurement accuracy.

Characterization and Antioxidant Evaluation of Four Kinds of Marine Oils in vitro.

The objective of this study was to characterize the lipid class and fatty acid composition of four kinds of marine oils including Phaeodactylum tricornutum oil (PO), Laminaria japonica oil (LO), krill oil (KO) and fish oil (FO), and evaluate their antioxidant capacities in vitro. The results indicated that compared to other three oils, PO showed the highest contents of total lipids and fucoxanthin (194.70 and 7.48 mg/g dry weight, respectively), the relatively higher content of long-chain polyunsaturated fatty acids including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (30.94 % in total fatty acids), and total phenolic content (675.88 mg gallic acid equivalent /100 g lipids), thereby contribute to great advantages in scavenging free radicals such as 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2-azino-bis (3-ethylbenzthiazoline)-6-sulfonic acid (ABTS), peroxyl radical, as well as reducing FRAP value. In conclusion, PO should be considered as a potential ingredient for dietary supplement with antioxidant capacity.

The Impact of Providing Free HIV Self-testing on Sexual Risk Behaviors Among Men who have Sex with Men in Hunan, China: A Randomized Controlled Trial.

HIV self-testing (HIVST) increases testing frequency among men who have sex with men (MSM). However, its impact on sexual risk behaviors is unclear. In a randomized controlled trial conducted in Hunan Province, China, HIV-negative MSM were randomized to receive one of two interventions for one year: (1) facility-based HIV testing, or (2) facility-based HIV testing augmented with free HIVST. From April to June 2018, 230 MSM were enrolled. They self-reported sexual behaviors every 3 months for 12 months. Among 216 MSM with follow-ups (intervention: 110; control: 106), adjusting for potential confounders in Generalized Estimating Equation models, there were no statistically significant differences in consistent condom use with male partners (regular/casual) or female partners, nor on number of male or female sexual partners. Provision of free HIVST kits does not increase risky sex and should be included in comprehensive HIV prevention packages, particularly for sexual minority men in China.

Pentacyclic triterpenoids from spikes of Prunella vulgaris L. with thyroid tumour cell cytostatic bioactivities.

Five new triterpenoids, including four ursane types (1-4) and one oleanane type (5), together with 15 known ursane types pentacyclic triterpenoids (6-20) were isolated from the fruit spikes of Prunella vulgaris L., a traditional Chinese herbal medicine. Their structures were elucidated based on IR, HR-ESI-MS, and NMR spectroscopic data. The SW579 cell line was used to evaluate anti-thyroid cancer activities of (1-20). The results indicated that (7-9), (16), and (19) exhibited apparent inhibitory activity with IC50 values of 25.73-71.41 µM (cisplatin as positive control, IC50 14.49 ± 0.97 µM). Network pharmacology and molecular docking were also used for the prediction of the synergistic actions and the underlying mechanisms. Accordingly, four potential targets have been characterized.

Efficacy of a smartphone-based care support programme in improving post-traumatic stress in families with childhood cancer: protocol of a randomised controlled trial.

INTRODUCTION: Diagnosis and treatment represent distressing experiences for the families of children with cancer. Psychosocial challenges are faced by these families in China because of limited health services and resources for psychosocial oncology care. Effective interventions tailored to the knowledge level and cultural values of this population are needed. The goal of this study is to evaluate a smartphone-based care support (SBCS) programme for the families of children with cancer in China. METHODS AND ANALYSIS: A parallel randomised controlled trial will be conducted to examine the efficacy of an evidence-based and culturally tailored SBCS programme for the families of children with cancer in China. A total of 180 families will be recruited. The intervention will consist of an introduction session and four main sessions and will be conducted sequentially on a single weekend day. Participating families will be included in the intervention group. The post-traumatic stress and quality of life of families will be evaluated at baseline, during the intervention, immediately after the intervention, and 2 and 6 months after the intervention. ETHICS AND DISSEMINATION: Ethical approval for this protocol has been obtained from the Nursing and Behavioural Medicine Research Ethics Review Committee, Xiangya School of Nursing, Central South University (Protocol #: E2020125). The findings of the trial will be disseminated through conference presentations and publications in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2000040510.

Incidence and mortality of non-AIDS-defining cancers among people living with HIV: A systematic review and meta-analysis.

Background: Non-AIDS-defining cancers (NADCs) are now becoming a rising cause of morbidity among people living with HIV (PLHIV) in the highly active antiretroviral therapy (HAART) era. We conducted a systematic review and meta-analysis to estimate the summary risk of incidence and mortality of a wide range of NADCs among PLHIV compared with the general population. Methods: This systematic review and meta-analysis was registered in the PROSPERO (registration number CRD42020222020). We searched PubMed, EMBASE, Cochrane library, and Web of Science for relevant studies published before Jan 24, 2022. Cohort or registry linkage studies comparing the incidence or mortality of individual NADCs in PLHIV with that in the general population were included. Studies simply reporting outcomes of cancer precursor lesions or combined NADCs were excluded. We calculated pooled standardised incidence (SIRs) and standardised mortality ratios (SMRs) and their 95% confidence intervals (CIs) using random-effects models, and used robust variance estimation to account for non-independence in study-level effect sizes. Findings: We identified 92 publications arising from 46 independent studies including 7 articles out of 7 studies from developing countries. Among the 40 types of NADCs investigated, all of the 20 infection-related NADCs, cancers related with human papillomavirus infection in particular, and half of the 20 non-infection-related NADCs occurred in excess in PLHIV compared with the general population. This risk pattern was consistent in most WHO regions and in both high-income and low-and middle-income countries. The increased SIRs for various NADCs were more evident among PLHIV with advanced immunodeficiency, and was explored by HIV transmission route, and use of HAART. PLHIV had increased mortality for anal cancer (SMR 124·07, 95% CI 27·31-563·72), Hodgkin lymphoma (41·03, 2·91-577·88), liver cancer (8·36, 3·86-18·11), lung cancer (3·95, 1·52-10·26), and skin melanoma (3·95, 1·28-12·2). Interpretation: PLHIV had increased incidence and mortality for a wide spectrum of NADCs. Primary prevention and effective treatment for NADCs in this population is urgently needed. Funding: Natural Science Foundation of China Excellent Young Scientists Fund, Natural Science Foundation of China International/Regional Research Collaboration Project, National Science and Technology Major Project of China, Sanming Project of Medicine in Shenzhen, High Level Project of Medicine in Longhua, Shenzhen, Shenzhen Science and Technology Innovation Commission Basic Research Program, Special Support Plan for High-Level Talents of Guangdong Province, the Guangzhou Basic Research Program on People's Livelihood Science and Technology, the National Natural Science Foundation of China.

Global burden of oropharyngeal cancer attributable to human papillomavirus by anatomical subsite and geographic region.

BACKGROUND: Oropharynx is the anatomical site with the highest human papillomavirus (HPV) infection in head and neck. Many studies on HPV prevalence and p16INK4a positivity in oropharyngeal cancer have been published in recent years. We aimed to update the global burden estimates of oropharyngeal cancer attributable to HPV with the latest data and estimate global burden of tonsillar cancer and base of tongue cancer attributable to HPV by region and country. METHODS: We calculated the number of new cancer cases using the Cancer Incidence in Five Continents Volume XI (CI5XI) and country-specific population in 2012 issued by the United Nations. Estimates of HPV prevalence and p16INK4a positivity were obtained from literature search and pooled analyses where necessary. RESULTS: Globally the number of oropharyngeal cancer and tonsillar cancer attributable to HPV were 42,000 and 20,000 in 2012, corresponding to AFs of 42.7% and 52.7%. The number of cancer cases attributable to HPV among males was about 4-fold greater than that among females. For both oropharyngeal cancer and tonsillar cancer, AFs were higher in more developed countries. Among HPV positive oropharyngeal cancer cases, 86.7%, 87.8%, and 92.5% could have been prevented by bivalent (2v), quadrivalent (4v), and nonavalent (9v) HPV vaccines. CONCLUSIONS: It is worth considering the inclusion of HPV immunization in males, especially in the regions where oropharyngeal cancer is highly prevalent.

Guhong injection promotes post-stroke functional recovery via attenuating cortical inflammation and apoptosis in subacute stage of ischemic stroke.

BACKGROUND: As a leading cause of death and disability, alternative therapies for stroke are still limited by its complicated pathophysiological manifestations. Guhong injection (GHI), consisting of safflower aqueous extract and aceglutamide, has been widely applied for the clinical treatment of cerebrovascular diseases, especially ischemic stroke and post-stroke recovery, in China. Recently, a series of studies have reported the positive effect of GHI against cerebral ischemia/reperfusion injury via targeting various molecular mechanisms. However, questions remain on whether treatment with GHI contributes to better functional recovery after stroke and if so, the potential mechanisms and active substances. PURPOSE: The aim of this work was to explore the potential therapeutic possibilities of GHI for the neurological and behavioral recovery after stroke and to investigate the underlying molecular mechanisms as well as active substances. METHODS: The neural and motor deficits as well as cortical lesions after GHI treatment were investigated in a mouse model of transient ischemic stroke. Based on the substance identification of GHI, network pharmacology combined with an experimental verification method was used to systematically decipher the biological processes and signaling pathways closely related to GHI intervention in response to post-stroke functional outcomes. Subsequently, ingenuity pathway analysis (IPA) analysis was performed to determine the anti-stroke active substances targeting to the hub targets involved in the significant molecular pathways regulated by GHI treatment. RESULTS: Therapeutically, administration of GHI observably ameliorated the post-stroke recovery of neural and locomotor function as well as reduced infarct volume and histopathological damage to the cerebral cortex in subacute stroke mice. According to 26 identified or tentatively characterized substances in GHI, the compound-target-pathway network was built. Bioinformatics analysis suggested that inflammatory and apoptotic pathways were tightly associated with the anti-stroke effect of GHI. Based on protein-protein interaction network analysis, the hub targets (such as NF-κB p65, TNF-α, IL-6, IL-1ß, Bax, Bcl-2, and Caspase-3) involved in inflammation and apoptosis were selected. On the one hand, immunofluorescence and ELISA results showed that GHI (10 ml/kg) treatment obviously reduced NF-κB p65 nuclear translocation as well as decreased the abnormally elevated concentrations of proinflammatory cytokines (TNF-α, IL-6, and IL-1ß) in damaged cortex tissues. On the other hand, GHI (10 ml/kg) treatment significantly downregulated the number of TUNEL-positive apoptotic cells in ischemic cortex and effectively restored the abnormal expression of Bax, Bcl-2, and Caspase-3. Based on the results of IPA, hydroxysafflor yellow A, baicalin, scutellarin, gallic acid, syringin, chlorogenic acid, kaempferol, kaempferol-3-O-ß-rutinoside, and rutin acted synergistically on core targets, which could be considered as the active substances of GHI. CONCLUSION: Overall, the current findings showed that the beneficial action of GHI on improving post-stroke functional recovery of subacute stroke mice partly via the modulation of cortical inflammation and apoptosis. These findings not only provide a reliable reference for the clinical application of GHI, but also shed light on a promising alternative therapeutic strategy for ischemic stroke patients.

A Putative Effector CcSp84 of Cytospora chrysosperma Localizes to the Plant Nucleus to Trigger Plant Immunity.

Cytospora chrysosperma is the main causal agent of poplar canker disease in China, especially in some areas with poor site conditions. Pathogens secrete a large number of effectors to interfere the plant immunity and promote their infection and colonization. Nevertheless, the roles of effectors in C. chrysosperma remain poorly understood. In this study, we identified and functionally characterized a candidate effector CcSp84 from C. chrysosperma, which contained a nuclear localization signal motif at the C-terminal and was highly induced during infection stages. Transient expression of CcSp84 in Nicotiana benthamiana leaves could trigger cell death. Additionally, deletion of CcSp84 significantly reduced fungal virulence to the polar twigs, while no obvious defects were observed in fungal growth and sensitivity to H2O2. Confocal microscopy revealed that CcSp84 labeled with a green fluorescent protein (GFP) was mainly accumulated in the plant nucleus. Further analysis revealed that the plant nucleus localization of CcSp84 was necessary to trigger plant immune responses, including ROS accumulation, callose deposition, and induced expression of jasmonic acid and ethylene defense-related genes. Collectively, our results suggest that CcSp84 is a virulence-related effector, and plant nucleus localization is required for its functions.

Acceptability of male circumcision for HIV prevention among men who have sex with men in China: a short report.

Recent evidence shows that circumcision is associated with lower HIV prevalence among MSM. We assessed the acceptability of circumcision for preventing HIV and that of Shang Ring circumcision (SRC) among men who have sex with men (MSM) in China. 538 adult MSM were recruited from six cities in China between January and March 2019. Participants were surveyed by an online, self-administered questionnaire. The acceptability of circumcision was assessed before and after the potential protective effect of circumcision against HIV was informed, and subsequently men's willingness to undergo SRC was assessed. The level of circumcision was 16.4%. Of 450 uncircumcised MSM, their willingness to be circumcised in the following six months increased significantly from 32.2% to 55.6% after the information session. Three quarters of men who were willing to undergo circumcision accepted SRC. MSM who perceived that circumcision could maintain genital hygiene were more likely to accept circumcision after the information session, whereas those who regarded circumcision as an embarrassing surgery were disinclined to be circumcised. The low circumcision rate, along with its high acceptability in Chinese MSM, suggests a great potential benefit of circumcision intervention if proved effective. SRC might be a popular circumcision procedure in this population.

Using protection motivation theory to explain the intention to initiate human papillomavirus vaccination among men who have sex with men in China.

BACKGROUND: Human papillomavirus (HPV) infection and related diseases are common among men who have sex with men (MSM). The most effective prevention is HPV vaccination. In China, however, men are not included in the HPV vaccination plan. We investigated the intention to initiate HPV vaccination and associated factors among MSM in China. Methods We surveyed 563 unvaccinated MSM aged 18 or older from six cities in China. Participants completed an electronic questionnaire about demographics, knowledge of and attitude towards HPV and HPV vaccine, intention to initiate HPV vaccination, willingness to recommend HPV vaccine to peers, feeling about government policy about HPV vaccination. We used the structural equation modeling (SEM) to analyze factors associated with HPV vaccine intention. Results The knowledge of HPV and HPV vaccine among participants was low. The mean score of knowledge about HPV and HPV vaccine was only 1.59 (range 0-11). The intention to initiate HPV vaccination within 6 months among participants was moderate (43.3% in total, 18.1% for 'very high' and 25.2% for 'above average').

iCAL: a new pipeline to investigate autophagy selectivity and cancer.

Macroautophagy/autophagy can selectively degrade misfolded proteins, damaged organelles and other cargoes. It is conceivable that alteration of the degradation processes could disrupt normal cellular signaling and contribute to human diseases such as cancer. To explore the link between aberrant autophagy selectivity and human cancer, we have developed a pipeline called "inference of cancer-associated LC3-interacting region-containing proteins" (iCAL), which integrates a sequence-based predictor, a model-based computational method, publicly available cancer mutations, and multiple experimental approaches. Using iCAL, we have identified 222 LIR motif-associated mutations (LAMs) in 148 LIR-containing proteins (LIRCPs), and validated that LAMs in ATG4B, STBD1, EHMT2 and BRAF impair their interactions with LC3 and/or autophagy activities. Moreover, we uncovered that STBD1, a previously poorly-characterized protein, inhibits tumor growth via metabolism reprogramming in cancer cells. A patient-derived mutation in STBD1 (W203C) disrupts the interaction with LC3 and promotes tumor growth. Taken together, iCAL provides an exciting new avenue to discover novel autophagy pathways that contribute to carcinogenesis.

Model-based analysis uncovers mutations altering autophagy selectivity in human cancer.

Autophagy can selectively target protein aggregates, pathogens, and dysfunctional organelles for the lysosomal degradation. Aberrant regulation of autophagy promotes tumorigenesis, while it is far less clear whether and how tumor-specific alterations result in autophagic aberrance. To form a link between aberrant autophagy selectivity and human cancer, we establish a computational pipeline and prioritize 222 potential LIR (LC3-interacting region) motif-associated mutations (LAMs) in 148 proteins. We validate LAMs in multiple proteins including ATG4B, STBD1, EHMT2 and BRAF that impair their interactions with LC3 and autophagy activities. Using a combination of transcriptomic, metabolomic and additional experimental assays, we show that STBD1, a poorly-characterized protein, inhibits tumor growth via modulating glycogen autophagy, while a patient-derived W203C mutation on LIR abolishes its cancer inhibitory function. This work suggests that altered autophagy selectivity is a frequently-used mechanism by cancer cells to survive during various stresses, and provides a framework to discover additional autophagy-related pathways that influence carcinogenesis.

Mn, N, P-tridoped bamboo-like carbon nanotubes decorated with ultrafine Co2P/FeCo nanoparticles as bifunctional oxygen electrocatalyst for long-term rechargeable Zn-air battery.

Rational synthesis of cost-effectiveness, ultra-stable and high-efficiency bifunctional oxygen catalysts are pivotal for Zn-air batteries. Herein, fine Co2P/FeCo nanoparticles (NPs) anchored on Mn, N, P-codoped bamboo-like carbon nanotubes (Co2P/FeCo/MnNP-BCNTs) are constructed in the coexistence of melamine, poly(4-vinylpyridine) and adenosine-5'-diphosphate disodium salt (ADP) by convenient pyrolysis and follow-up acid treatment. The as-prepared catalyst exhibits the higher onset potential (Eonset = 0.97 V vs. RHE) and half-wave potential (E1/2 = 0.88 V vs. RHE) for oxygen reduction reaction (ORR), coupled with excellent oxygen evolution reaction (OER) with the lower overpotential of 324 mV at 10 mA cm-2. Notably, the home-made Zn-air battery delivers the greater peak power density of 220 mW cm-2, together with the outstanding cycling stability. The excellent performances of Co2P/FeCo/MnNP-BCNTs catalyst are mainly attributed to the highly conductive carbon nanotubes and the synergistic effects between carbon nanotubes and Co2P/FeCo NPs. This work offers a novel strategy to explore advanced bifunctional oxygen catalysts for high-efficiency metal-air batteries.

The Cytospora chrysosperma Virulence Effector CcCAP1 Mainly Localizes to the Plant Nucleus To Suppress Plant Immune Responses.

Canker disease is caused by the fungus Cytospora chrysosperma and damages a wide range of woody plants, causing major losses to crops and native plants. Plant pathogens secrete virulence-related effectors into host cells during infection to regulate plant immunity and promote colonization. However, the functions of C. chrysosperma effectors remain largely unknown. In this study, we used Agrobacterium tumefaciens-mediated transient expression system in Nicotiana benthamiana and confocal microscopy to investigate the immunoregulation roles and subcellular localization of CcCAP1, a virulence-related effector identified in C. chrysosperma CcCAP1 was significantly induced in the early stages of infection and contains cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins (CAP) superfamily domain with four cysteines. CcCAP1 suppressed the programmed cell death triggered by Bcl-2-associated X protein (BAX) and the elicitin infestin1 (INF1) in transient expression assays with Nicotiana benthamiana The CAP superfamily domain was sufficient for its cell death-inhibiting activity and three of the four cysteines in the CAP superfamily domain were indispensable for its activity. Pathogen challenge assays in N. benthamiana demonstrated that transient expression of CcCAP1 promoted Botrytis cinerea infection and restricted reactive oxygen species accumulation, callose deposition, and defense-related gene expression. In addition, expression of green fluorescent protein-labeled CcCAP1 in N. benthamiana showed that it localized to both the plant nucleus and the cytoplasm, but the nuclear localization was essential for its full immune inhibiting activity. These results suggest that this virulence-related effector of C. chrysosperma modulates plant immunity and functions mainly via its nuclear localization and the CAP domain.IMPORTANCE The data presented in this study provide a key resource for understanding the biology and molecular basis of necrotrophic pathogen responses to Nicotiana benthamiana resistance utilizing effector proteins, and CcCAP1 may be used in future studies to understand effector-triggered susceptibility processes in the Cytospora chrysosperma-poplar interaction system.

Iron, manganese co-doped Ni3S2 nanoflowers in situ assembled by ultrathin nanosheets as a robust electrocatalyst for oxygen evolution reaction.

Exploring high-performance and stable transition metal electrocatalysts is prerequisite for boosting overall water splitting efficiency. In this study, iron (Fe), manganese (Mn) co-doped three-dimensional (3D) Ni3S2 nanoflowers were in situ assembled by many inter-connected 2D nanosheets on nickel foam (NF) via hydrothermal and sulfuration treatment. By virtue of the introduced Fe and Mn elements and unique flower-like structures, the as-prepared catalyst displayed high activity and stability for oxygen evolution reaction (OER), coupled with a small Tafel slope (63.29 mV dec-1) and a low overpotential of 216 mV to reach the current density of 30 mA cm-2. This study would shed some lights for facile synthesis of exceptional OER catalyst by tailoring the electronic structure and doping transition metal(s).