A Pan-Cancer Analysis of Enhancer Expression in Nearly 9000 Patient Samples.

The role of enhancers, a key class of non-coding regulatory DNA elements, in cancer development has increasingly been appreciated. Here, we present the detection and characterization of a large number of expressed enhancers in a genome-wide analysis of 8928 tumor samples across 33 cancer types using TCGA RNA-seq data. Compared with matched normal tissues, global enhancer activation was observed in most cancers. Across cancer types, global enhancer activity was positively associated with aneuploidy, but not mutation load, suggesting a hypothesis centered on "chromatin-state" to explain their interplay. Integrating eQTL, mRNA co-expression, and Hi-C data analysis, we developed a computational method to infer causal enhancer-gene interactions, revealing enhancers of clinically actionable genes. Having identified an enhancer ∼140 kb downstream of PD-L1, a major immunotherapy target, we validated it experimentally. This study provides a systematic view of enhancer activity in diverse tumor contexts and suggests the clinical implications of enhancers.

Structure-based characterization and compound identification of the wild-type THF class-II riboswitch.

Riboswitches are conserved regulatory RNA elements participating in various metabolic pathways. Recently, a novel RNA motif known as the folE RNA motif was discovered upstream of folE genes. It specifically senses tetrahydrofolate (THF) and is therefore termed THF-II riboswitch. To unravel the ligand recognition mechanism of this newly discovered riboswitch and decipher the underlying principles governing its tertiary folding, we determined both the free-form and bound-form THF-II riboswitch in the wild-type sequences. Combining structural information and isothermal titration calorimetry (ITC) binding assays on structure-based mutants, we successfully elucidated the significant long-range interactions governing the function of THF-II riboswitch and identified additional compounds, including alternative natural metabolites and potential lead compounds for drug discovery, that interact with THF-II riboswitch. Our structural research on the ligand recognition mechanism of the THF-II riboswitch not only paves the way for identification of compounds targeting riboswitches, but also facilitates the exploration of THF analogs in diverse biological contexts or for therapeutic applications.

Integrative approaches based on genomic techniques in the functional studies on enhancers.

With the development of sequencing technology and the dramatic drop in sequencing cost, the functions of noncoding genes are being characterized in a wide variety of fields (e.g. biomedicine). Enhancers are noncoding DNA elements with vital transcription regulation functions. Tens of thousands of enhancers have been identified in the human genome; however, the location, function, target genes and regulatory mechanisms of most enhancers have not been elucidated thus far. As high-throughput sequencing techniques have leapt forwards, omics approaches have been extensively employed in enhancer research. Multidimensional genomic data integration enables the full exploration of the data and provides novel perspectives for screening, identification and characterization of the function and regulatory mechanisms of unknown enhancers. However, multidimensional genomic data are still difficult to integrate genome wide due to complex varieties, massive amounts, high rarity, etc. To facilitate the appropriate methods for studying enhancers with high efficacy, we delineate the principles, data processing modes and progress of various omics approaches to study enhancers and summarize the applications of traditional machine learning and deep learning in multi-omics integration in the enhancer field. In addition, the challenges encountered during the integration of multiple omics data are addressed. Overall, this review provides a comprehensive foundation for enhancer analysis.

BCKDK modification enhances the anticancer efficacy of CAR-T cells by reprogramming branched chain amino acid metabolism.

Altered branched chain amino acids (BCAAs), including leucine, isoleucine, and valine, are frequently observed in patients with advanced cancer. We evaluated the efficacy of chimeric antigen receptor (CAR) T cell-mediated cancer cell lysis potential in the immune microenvironment of BCAA supplementation and deletion. BCAA supplementation increased cancer cell killing percentage, while accelerating BCAA catabolism and decreasing BCAA transporter decreased cancer cell lysis efficacy. We thus designed BCKDK engineering CAR T cells for the reprogramming of BCAA metabolism in the tumor microenvironment based on the genotype and phenotype modification. BCKDK overexpression (OE) in CAR-T cells significantly improved cancer cell lysis, while BCKDK knockout (KO) resulted in inferior lysis potential. In an in vivo experiment, BCKDK-OE CAR-T cell treatment significantly prolonged the survival of mice bearing NALM6-GL cancer cells, with the differentiation of central memory cells and an increasing proportion of CAR-T cells in the peripheral circulation. BCKDK-KO CAR-T cell treatment resulted in shorter survival and a decreasing percentage of CAR-T cells in the peripheral circulation. In conclusion, BCKDK-engineered CAR-T cells exert a distinct phenotype for superior anticancer efficiency.

Structure-based investigations of the NAD+-II riboswitch.

Riboswitches are conserved non-coding domains in bacterial mRNA with gene regulation function that are essential for maintaining enzyme co-factor metabolism. Recently, the pnuC RNA motif was reported to selectively bind nicotinamide adenine dinucleotide (NAD+), defining a novel class of NAD+ riboswitches (NAD+-II) according to phylogenetic analysis. To reveal the three-dimensional architecture and the ligand-binding mode of this riboswitch, we solved the crystal structure of NAD+-II riboswitch in complex with NAD+. Strikingly and in contrast to class-I riboswitches that form a tight recognition pocket for the adenosine diphosphate (ADP) moiety of NAD+, the class-II riboswitches form a binding pocket for the nicotinamide mononucleotide (NMN) portion of NAD+ and display only unspecific interactions with the adenosine. We support this finding by an additional structure of the class-II RNA in complex with NMN alone. The structures define a novel RNA tertiary fold that was further confirmed by mutational analysis in combination with isothermal titration calorimetry (ITC), and 2-aminopurine-based fluorescence spectroscopic folding studies. Furthermore, we truncated the pnuC RNA motif to a short RNA helical scaffold with binding affinity comparable to the wild-type motif to allude to the potential of engineering the NAD+-II motif for biotechnological applications.

Designable Nanoadaptor for Enhanced Recognition of Natural Killer Cell to Tumor via Bio-orthogonal Click Reaction.

Highly efficient recognition of cancer cells by immune cells is important for successful therapeutic-cell-based cancer immunotherapy. Herein, we present a facile NIR-II nanoadaptor [hyaluronic acid (HA)/dibenzocyclooctyne (DBCO)-Au:Ag2Te quantum dots (QDs)] for enhancing the tumor recognition and binding ability of natural killer (NK) cells via a bio-orthogonal click reaction in vivo. The Nanoadaptor possesses superior tumor-targeting capacity, facilitating the accumulation of the chemical receptor DBCO at the tumor sites. Subsequently, the enrichment of DBCO on tumor cell surfaces provides multivalent recognition sites for capturing pretreated azide engineered NK92 cells (NK92-N3) through an efficient click reaction, thereby significantly enhancing the therapeutical efficiency. The dynamic process of nanoadaptor-mediated recognition of NK cells to tumor cells could be vividly observed using multiplexed NIR-II fluorescence imaging in a mouse model of lung cancer. Such a nanoadaptor strategy can be extended to other therapeutic cellular systems and holds promise for future clinical applications.

Programmed Remodeling of the Tumor Milieu to Enhance NK Cell Immunotherapy Combined with Chemotherapy for Pancreatic Cancer.

Natural killer (NK) cell-based adoptive immunotherapy has demonstrated encouraging therapeutic effects in clinical trials for hematological cancers. However, the effectiveness of treatment for solid tumors remains a challenge due to insufficient recruitment and infiltration of NK cells into tumor tissues. Herein, a programmed nanoremodeler (DAS@P/H/pp) is designed to remodel dense physical stromal barriers and for dysregulation of the chemokine of the tumor environment to enhance the recruitment and infiltration of NK cells in tumors. The DAS@P/H/pp is triggered by the acidic tumor environment, resulting in charge reversal and subsequent hyaluronidase (HAase) release. HAase effectively degrades the extracellular matrix, promoting the delivery of immunoregulatory molecules and chemotherapy drugs into deep tumor tissues. In mouse models of pancreatic cancer, this nanomediated strategy for the programmed remodeling of the tumor microenvironment significantly boosts the recruitment of NK92 cells and their tumor cell-killing capabilities under the supervision of multiplexed near-infrared-II fluorescence.

Olink Proteomics for the Identification of Biomarkers for Early Diagnosis of Postmenopausal Osteoporosis.

This investigation aims to employ Olink proteomics in analyzing the distinct serum proteins associated with postmenopausal osteoporosis (PMOP) and identifying prognostic markers for early detection of PMOP via molecular mechanism research on postmenopausal osteoporosis. Postmenopausal women admitted to Beijing Jishuitan Hospital were randomly selected and categorized into three groups based on their dual-energy X-ray absorptiometry (DXA) T-scores: osteoporosis group (n = 24), osteopenia group (n = 20), and normal bone mass group (n = 16). Serum samples from all participants were collected for clinical and bone metabolism marker measurements. Olink proteomics was utilized to identify differentially expressed proteins (DEPs) that are highly associated with postmenopausal osteoporosis. The functional analysis of DEPs was performed using Gene Ontology and Kyto Encyclopedia Genes and Genomes (KEGG). The biological characteristics of these proteins and their correlation with PMOP were subsequently analyzed. ROC curve analysis was performed to identify potential biomarkers with the highest diagnostic accuracy for early stage PMOP. Through Olink proteomics, we identified five DEPs highly associated with PMOP, including two upregulated and three downregulated proteins. TWEAK and CDCP1 markers exhibited the highest area under the curve (0.8188 and 0.8031, respectively). TWEAK and CDCP1 have the potential to serve as biomarkers for early prediction of postmenopausal osteoporosis.

Strategic Lacunes Associated With Mild Cognitive Impairment in Rural Chinese Older Adults: A Population-Based Study.

BACKGROUND: Lacunes are associated with cognitive impairment. We sought to identify strategic lacune locations associated with mild cognitive impairment (MCI) and subtypes of MCI among older adults, and further to examine the role of white matter hyperintensities and perivascular spaces in the association. METHODS: This population-based cross-sectional study included 1230 dementia-free participants in the brain magnetic resonance imaging substudy (2018-2020) in MIND-China (Multimodal Interventions to Delay Dementia and Disability in Rural China). Lacunes were visually identified in frontal lobe, parieto-occipital lobe, temporal lobe, insula, basal ganglia, thalamus, cerebellum, and brainstem. MCI, amnestic MCI (aMCI), and nonamnestic MCI (naMCI) were defined following the Petersen's criteria. Data were analyzed using logistic regression models. RESULTS: Of the 1230 participants (age, ≥60 years; mean age, 69.40; SD, 4.30 years; 58.5% women), lacunes were detected in 357 people and MCI was defined in 286 individuals, including 243 with aMCI and 43 with naMCI. Lacunes in the supratentorial area, internal capsula, putamen/pallidum, and insula was significantly associated with increased odds ratio of MCI (multivariable-adjusted odds ratio ranged 1.40-3.21; P<0.05) and aMCI (multivariable-adjusted odds ratio ranged 1.46-3.36; P<0.05), whereas lacunes in the infratentorial area and brainstem were significantly associated with naMCI (multivariable-adjusted odds ratio ranged 2.68-3.46; P<0.01). Furthermore, the associations of lacunes in insula and internal capsula with MCI and aMCI, as well as the associations of lacunes in infratentorial area and brainstem with naMCI were present independent of white matter hyperintensities volume and perivascular spaces number. CONCLUSIONS: Lacunes in the internal capsula, putamen/pallidum, insula, and brainstem may represent the strategic lacunes that are independently associated with MCI, aMCI, or naMCI in Chinese older adults. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1800017758.

Nanofluidic Membrane-Assisted Organic Electrochemical Transistors for Bioinspired Gustatory Sensation Based on Selective Cation Transport.

Natural organisms have evolved precise sensing systems relying on unique ion channels, which can efficiently perceive various physical/chemical stimuli based on ionic signal transmission in biological fluid environments. However, it is still a huge challenge to achieve extensive applications of the artificial counterparts as an efficient wet sensing platform due to the fluidity of the working medium. Herein, nanofluidic membranes with selective cation transport properties and solid-state organic electrochemical transistors (OECTs) with amplified signals are integrated together to mimic human gustatory sensation, achieving ionic gustatory reagent recognition and a portable configuration. Cu-HHTP nanofluidic membranes with selective cation transport through their uniform micropores are constructed first, followed by assembly with OECTs to form the designed nanofluidic membrane-assisted OECTs (nanofluidic OECTs). As a result, they can distinguish typically ionic gustatory reagents, and even ionic liquids (ILs), demonstrating enhanced gustatory perception performance under a wide concentration range (10-7-10-1 m) compared with those of conventional OECTs. The linear correlations between the response and the reagent concentration further indicate the promising potential for practical application as a next-generation sensing platform. It is suggested that nanofluidic membranes mediated intramembrane cation transport based on the steric hindrance effect, resulting in distinguishable and improved response to multiple ions.

Community engagement tools in HIV/STI prevention research.

PURPOSE OF REVIEW: Community engagement is key to the success of sustainable public health interventions. This review highlights recent published studies that describe the use of community-engaged methods in sexually transmitted infection (STI) prevention research. RECENT FINDINGS: We organized the findings using a socio-ecological model. At the individual level, communities were engaged through participation in formative research, short-term consultations and community advisory board participation, as well as co-creation activities. At the interpersonal level, studies reviewed described peer-led interventions that leverage the influence and guidance of peers, patient-led interventions in the form of patient navigation and notification, as well as those that mobilize social networks and the power of social relationships to promote health. At the organizational and community level, multisectoral, multifacility collaborations between community, government, and academic stakeholders were highlighted. At the policy and population level, communities were engaged through community dialogues to disseminate research findings, as well as in developing strategic frameworks and clinical guidelines. Digital tools have also been leveraged for effective community engagement. SUMMARY: Communities have an effective role to play in STI prevention and can be engaged at multiple levels. Future efforts may consider the use of community engagement tools highlighted in this review, including digital technologies that have the potential to reach more diverse end-users.

An oncogenic enhancer promotes melanoma progression via regulating ETV4 expression.

BACKGROUND: Enhancers are important gene regulatory elements that promote the expression of critical genes in development and disease. Aberrant enhancer can modulate cancer risk and activate oncogenes that lead to the occurrence of various cancers. However, the underlying mechanism of most enhancers in cancer remains unclear. Here, we aim to explore the function and mechanism of a crucial enhancer in melanoma. METHODS: Multi-omics data were applied to identify an enhancer (enh17) involved in melanoma progression. To evaluate the function of enh17, CRISPR/Cas9 technology were applied to knockout enh17 in melanoma cell line A375. RNA-seq, ChIP-seq and Hi-C data analysis integrated with luciferase reporter assay were performed to identify the potential target gene of enh17. Functional experiments were conducted to further validate the function of the target gene ETV4. Multi-omics data integrated with CUT&Tag sequencing were performed to validate the binding profile of the inferred transcription factor STAT3. RESULTS: An enhancer, named enh17 here, was found to be aberrantly activated and involved in melanoma progression. CRISPR/Cas9-mediated deletion of enh17 inhibited cell proliferation, migration, and tumor growth of melanoma both in vitro and in vivo. Mechanistically, we identified ETV4 as a target gene regulated by enh17, and functional experiments further support ETV4 as a target gene that is involved in cancer-associated phenotypes. In addition, STAT3 acts as a transcription factor binding with enh17 to regulate the transcription of ETV4. CONCLUSIONS: Our findings revealed that enh17 plays an oncogenic role and promotes tumor progression in melanoma, and its transcriptional regulatory mechanisms were fully elucidated, which may open a promising window for melanoma prevention and treatment.

Lipidomic signatures in patients with early-onset and late-onset Preeclampsia.

BACKGROUND: Preeclampsia is a pregnancy-specific clinical syndrome and can be subdivided into early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE) according to the gestational age of delivery. Patients with preeclampsia have aberrant lipid metabolism. This study aims to compare serum lipid profiles of normal pregnant women with EOPE or LOPE and screening potential biomarkers to diagnose EOPE or LOPE. METHODS: Twenty normal pregnant controls (NC), 19 EOPE, and 19 LOPE were recruited in this study. Untargeted lipidomics based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to compare their serum lipid profiles. RESULTS: The lipid metabolism profiles significantly differ among the NC, EOPE, and LOPE. Compared to the NC, there were 256 and 275 distinct lipids in the EOPE and LOPE, respectively. Furthermore, there were 42 different lipids between the LOPE and EOPE, of which eight were significantly associated with fetal birth weight and maternal urine protein. The five lipids that both differed in the EOPE and LOPE were DGTS (16:3/16:3), LPC (20:3), LPC (22:6), LPE (22:6), PC (18:5e/4:0), and a combination of them were a potential biomarker for predicting EOPE or LOPE. The receiver operating characteristic analysis revealed that the diagnostic power of the combination for distinguishing the EOPE from the NC and for distinguishing the LOPE from the NC can reach 1.000 and 0.992, respectively. The association between the lipid modules and clinical characteristics of EOPE and LOPE was investigated by the weighted gene co-expression network analysis (WGCNA). The results demonstrated that the main different metabolism pathway between the EOPE and LOPE was enriched in glycerophospholipid metabolism. CONCLUSIONS: Lipid metabolism disorders may be a potential mechanism of the pathogenesis of preeclampsia. Lipid metabolites have the potential to serve as biomarkers in patients with EOPE or LOPE. Furthermore, lipid metabolites correlate with clinical severity indicators for patients with EOPE and LOPE, including fetal birth weight and maternal urine protein levels.

Using crowdsourcing at an academic conference to develop STI testing messaging for public dissemination.

OBJECTIVES: We provide a guide to conducting a crowdsourcing activity at an international sexually transmitted infection (STI) conference to design public messaging about STI testing and disseminating that messaging via social media. METHODS: A speaker gave a presentation at a conference plenary session on the concepts of cocreation, crowdsourcing and designathons, and the application of these participatory approaches in public health research. To illustrate one of these approaches (crowdsourcing), attendees in the audience were asked to take part in a voluntary participatory activity, in which they would pair up with a fellow attendee sitting nearby and write down an idea on a blank notecard. Dyads were given 10 min to create an entry responding to the prompt, 'Write something that inspires gonorrhoea and/or chlamydia testing (eg, picture, jingle, rhyme)'. Each entry was judged by at least four independent judges on a scale of 0 (lowest quality) to 10 (highest quality) based on their innovation and potential to promote chlamydia/gonorrhoea testing. Scores were averaged to determine the finalist entries. RESULTS: We received 32 entries. The average score was 6.41 and scores ranged from 4.5 to 8 (median 6.63, IQR 5.75, 7.06). Half of entries (n=16) were slogans, 15.6% (n=5) were poems/rhymes, 12.5% (n=4) were memes/images, 9.4% (n=3) were programme implementation ideas, 3.1% (n=1) was a song verse, and 3.1% (n=1) was a video idea. One finalist entry was a meme and received 720 impressions, 120 engagements, 27 detail expands, 19 likes, 6 reposts and 1 response on Twitter. The second finalist entry was a slogan and received 242 impressions, 16 engagements, 6 detail expands, 4 likes and 2 reposts. CONCLUSIONS: Conducting crowdsourcing activities at future conferences may be an innovative, feasible way to develop and disseminate engaging and important STI and other health messaging to the public in a short period of time.

Stable Vortex Solitons Sustained by Localized Gain in a Cubic Medium.

We propose a simple dissipative system with purely cubic defocusing nonlinearity and nonuniform linear gain that can support stable localized dissipative vortex solitons with high topological charges without the utilization of competing nonlinearities and nonlinear gain or losses. Localization of such solitons is achieved due to an intriguing mechanism when defocusing nonlinearity stimulates energy flow from the ringlike region with linear gain to the periphery of the medium where energy is absorbed due to linear background losses. Vortex solitons bifurcate from linear gain-guided vortical modes with eigenvalues depending on topological charges that become purely real only at specific gain amplitudes. Increasing gain amplitude leads to transverse expansion of vortex solitons, but simultaneously it usually also leads to stability enhancement. Increasing background losses allows creation of stable vortex solitons with high topological charges that are usually prone to instabilities in conservative and dissipative systems. Propagation of the perturbed unstable vortex solitons in this system reveals unusual dynamical regimes, when instead of decay or breakup, the initial state transforms into stable vortex solitons with lower or sometimes even with higher topological charge. Our results suggest an efficient mechanism for the formation of nonlinear excited vortex-carrying states with suppressed destructive azimuthal modulational instabilities in a simple setting relevant to a wide class of systems, including polaritonic systems, structured microcavities, and lasers.

Mapping Online Community Spaces Through Online Focus Group Discussions Among Gay, Bisexual, and Other Men Who Have Sex With Men in Guangdong, China: Implications for Human Immunodeficiency Virus/Sexually Transmitted Disease Prevention Services.

BACKGROUND: Chinese gay, bisexual, and other men who have sex with men (GBMSM) face discrimination in many facility-based health services, thus increasing the importance of online engagement. The purpose of this study was to examine online GBMSM community spaces and implications for HIV/sexually transmitted disease prevention services. METHODS: We conducted a total of 6 online focus group discussions with Chinese GBMSM from Guangdong province on the chat-based platform WeChat in 2021. Focus group discussions were asynchronous, and participants were able to provide and map out online spaces that they had participated in and share their perspectives on online engagement. Data were analyzed through framework analysis. RESULTS: Overall, 48 participants participated. Most were mainly sexually attracted to men (n = 43; 90.0%) and never participated in in-person LGBTQ-related events (n = 29; 60.4%). Participants articulated a typology of online spaces along the axes of whether such spaces were Chinese platforms (vs. non-Chinese) or whether they were GBMSM-specific (vs. non-GBMSM-specific). Participants articulated several advantages of online spaces, including greater anonymity, opportunities for community building, sharing of sexual health information, and being able to meet other GBMSM more efficiently. Drawbacks included the lack of personal connection, lack of safety measures for youth, encountering deception and the use of fake profile pictures, and needing a virtual proxy network to access some websites. Participants provided suggestions to further improve their experiences of online spaces. CONCLUSIONS: Although broad-based, GBMSM-specific messaging can be implemented in Chinese, GBMSM-specific spaces, sexual health messaging may also reach niche GBMSM communities in a variety of non-GBMSM spaces.

A G-quadruplex-binding platinum complex induces cancer mitochondrial dysfunction through dual-targeting mitochondrial and nuclear G4 enriched genome.

BACKGROUND: G-quadruplex DNA (G4) is a non-canonical structure forming in guanine-rich regions, which play a vital role in cancer biology and are now being acknowledged in both nuclear and mitochondrial (mt) genome. However, the impact of G4-based targeted therapy on both nuclear and mt genome, affecting mt function and its underlying mechanisms remain largely unexplored. METHODS: The mechanisms of action and therapeutic effects of a G4-binding platinum(II) complex, Pt-ttpy, on mitochondria were conducted through a comprehensive approaches with in vitro and in vivo models, including ICP-MS for platinum measurement, PCR-based genetic analysis, western blotting (WB), confocal microscope for mt morphology study, extracellular flux analyzer, JC1 and Annexin V apoptosis assay, flow cytometry and high content microscope screening with single-cell quantification of both ROS and mt specific ROS, as well as click-chemistry for IF study of mt translation. Decipher Pt-ttpy effects on nuclear-encoded mt related genes expression were undertaken via RNA-seq, Chip-seq and CUT-RUN assays. RESULTS: Pt-ttpy, shows a highest accumulation in the mitochondria of A2780 cancer cells as compared with two other platinum(II) complexes with no/weak G4-binding properties, Pt-tpy and cisplatin. Pt-ttpy induces mtDNA deletion, copy reduction and transcription inhibition, hindering mt protein translation. Functional analysis reveals potent mt dysfunction without reactive oxygen species (ROS) induction. Mechanistic study provided first evidence that most of mt ribosome genes are highly enriched in G4 structures in their promoter regions, notably, Pt-ttpy impairs most nuclear-encoded mt ribosome genes' transcription through dampening the recruiting of transcription initiation and elongation factors of NELFB and TAF1 to their promoter with G4-enriched sequences. In vivo studies show Pt-ttpy's efficient anti-tumor effects, disrupting mt genome function with fewer side effects than cisplatin. CONCLUSION: This study underscores Pt-ttpy as a G4-binding platinum(II) complex, effectively targeting cancer mitochondria through dual action on mt and nuclear G4-enriched genomes without inducing ROS, offering promise for safer and effective platinum-based G4-targeted cancer therapy.

Contributions of Surface Oxidizing Species and Cu+ to the Antibacterial Activities of Cu2O with Different Crystalline Structures.

Although precise regulation of the crystalline structures of metal oxides is an effective method to improve their antibacterial activities, the corresponding mechanisms involved in this process are still unclear. In this study, three kinds of cuprous oxide (Cu2O) samples with different structures of cubes, octahedra, and rhombic dodecahedra (c-Cu2O, o-Cu2O, and r-Cu2O) have been successfully synthesized and their antibacterial activities are compared. The antibacterial activities follow the order of r-Cu2O > o-Cu2O > c-Cu2O, revealing the significant dependence of the antibacterial activities on the crystalline structures of Cu2O. Quenching experiments, as well as the NBT and DPD experiments indicate that ≡CuII─OO• superoxo and ≡CuII─OOH peroxo, instead of •OH, O2•-, and H2O2, are the primary oxidizing species in the oxidative damage to E. coli. Raman analysis further confirms the presence of both ≡CuII─OO• superoxo and ≡CuII─OOH peroxo on the surface of r-Cu2O. On the other hand, the NCP experiment reveals that Cu+, instead of Cu2+, also contributes to the antibacterial process. This study provides new insight into the antibacterial mechanisms of Cu2O.

Al(OTf)3-Catalyzed Regioselective N2-Arylation of Tetrazoles with Diazo Compounds.

Regioselective methods to access alkylated tetrazoles still remain a challenging goal. Herein, we describe a novel regioselective protocol for N2-arylation of tetrazoles with diazo compounds using inexpensive Al(OTf)3. This reaction could be conducted under mild conditions to access a diverse array of alkylated tetrazoles with 2-substituted tetrazoles as the major products, demonstrating a comprehensive range of substrate compatibility and excellent functional group compatibility. Mechanistic studies revealed a carbene-free process in this reaction procedure. Furthermore, the scale-up reaction and transformations of the N2-arylation of tetrazole products demonstrated the potential of this strategy.

Disparities in HIV incidence and mortality rates between Japanese nationals and international migrants before and during the COVID-19 pandemic: evidence from Japan's national HIV surveillance data (2018-2021).

Migrants often encounter heightened health risks during crises. We analysed the disparities in the burden of HIV between Japanese nationals and international migrants in Japan by comparing new HIV infections, AIDS cases, and HIV-related deaths between 2018-2019 (pre-COVID-19) and 2020-2021 (during the COVID-19 pandemic). Between 2018 and 2021, 4,705 new HIV infections were reported in Japan (2,813 Japanese nationals and 522 international migrants). Additionally, 1,370 AIDS cases (1,188 Japanese nationals, 182 international migrants) were recorded, representing 29.1% of the total. Comparative analysis of HIV incidence and mortality rates between Japanese nationals and international migrants indicates elevated disparities: During the COVID-19 pandemic, the HIV incidence rate among Japanese nationals decreased from 1.8 to 1.5 cases/100,000 people, while the rate among international migrants remained high at 12.8 cases/100,000 people. The AIDS incidence also increased for international migrants from 2.8 to 3.8 per 100,000 people, while Japanese nationals maintained a low at 0.5 per 100,000 people. International migrants living with HIV experienced a significantly younger age at death due to HIV-related illness (coefficient = -11.7, p < .01). The COVID-19 pandemic may have exacerbated the disparities with more international migrants living with HIV being diagnosed late and with less precise reporting. Investment in more equitable HIV care is warranted.