Expansin SlExp1 and endoglucanase SlCel2 synergistically promote fruit softening and cell wall disassembly in tomato.

Fruit softening, an irreversible process that occurs during fruit ripening, can lead to losses and waste during postharvest transportation and storage. Cell wall disassembly is the main factor leading to loss of fruit firmness, and several ripening-associated cell wall genes have been targeted for genetic modification, particularly pectin modifiers. However, individual knockdown of most cell wall-related genes has had minimal influence on cell wall integrity and fruit firmness, with the notable exception of pectate lyase. Compared to pectin disassembly, studies of the cell wall matrix, the xyloglucan-cellulose framework, and underlying mechanisms during fruit softening are limited. Here, a tomato (Solanum lycopersicum) fruit ripening-associated α-expansin (SlExpansin1/SlExp1) and an endoglucanase (SlCellulase2/SlCel2), which function in the cell wall matrix, were knocked out individually and together using clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9-mediated genome editing. Simultaneous knockout of SlExp1 and SlCel2 enhanced fruit firmness, reduced depolymerization of homogalacturonan-type pectin and xyloglucan, and increased cell adhesion. In contrast, single knockouts of either SlExp1 or SlCel2 did not substantially change fruit firmness, while simultaneous overexpression of SlExp1 and SlCel2 promoted early fruit softening. Collectively, our results demonstrate that SlExp1 and SlCel2 synergistically regulate cell wall disassembly and fruit softening in tomato.

Deciphering PDH1's role in mung bean domestication: a genomic perspective on pod dehiscence.

Mung bean (Vigna radiata) stands as a crucial legume crop in Asia, contributing to food security. However, our understanding of the underlying genetic foundation governing domesticated agronomic traits, especially those linked to pod architecture, remains largely unexplored. In this study, we delved into the genomic divergence between wild and domesticated mung bean varieties, leveraging germplasm obtained from diverse sources. Our findings unveiled pronounced variation in promoter regions (35%) between the two mung bean subpopulations, suggesting substantial changes in gene expression patterns during domestication. Leveraging transcriptome analysis using distinct reproductive stage pods and subpopulations, we identified candidate genes responsible for pod and seed architecture development, along with Genome-Wide Association Studies (GWAS) and Quantitative Trait Locus (QTL) analysis. Notably, our research conclusively confirmed PDH1 as a parallel domesticated gene governing pod dehiscence in legumes. This study imparts valuable insights into the genetic underpinnings of domesticated agronomic traits in mung bean, and simultaneously highlighting the parallel domestication of pivotal traits within the realm of legume crops.

SoyDNGP: a web-accessible deep learning framework for genomic prediction in soybean breeding.

Soybean is a globally significant crop, playing a vital role in human nutrition and agriculture. Its complex genetic structure and wide trait variation, however, pose challenges for breeders and researchers aiming to optimize its yield and quality. Addressing this biological complexity requires innovative and accurate tools for trait prediction. In response to this challenge, we have developed SoyDNGP, a deep learning-based model that offers significant advancements in the field of soybean trait prediction. Compared to existing methods, such as DeepGS and DNNGP, SoyDNGP boasts a distinct advantage due to its minimal increase in parameter volume and superior predictive accuracy. Through rigorous performance comparison, including prediction accuracy and model complexity, SoyDNGP represents improved performance to its counterparts. Furthermore, it effectively predicted complex traits with remarkable precision, demonstrating robust performance across different sample sizes and trait complexities. We also tested the versatility of SoyDNGP across multiple crop species, including cotton, maize, rice and tomato. Our results showed its consistent and comparable performance, emphasizing SoyDNGP's potential as a versatile tool for genomic prediction across a broad range of crops. To enhance its accessibility to users without extensive programming experience, we designed a user-friendly web server, available at http://xtlab.hzau.edu.cn/SoyDNGP. The server provides two features: 'Trait Lookup', offering users the ability to access pre-existing trait predictions for over 500 soybean accessions, and 'Trait Prediction', allowing for the upload of VCF files for trait estimation. By providing a high-performing, accessible tool for trait prediction, SoyDNGP opens up new possibilities in the quest for optimized soybean breeding.

α-Catenin promotes dermal fibroblasts proliferation and migration during wound healing via FAK/YAP activation.

Skin wound healing is a complex and organized biological process, and the dermal fibroblasts play a crucial role. α-Catenin is known to be involved in regulating various cellular signals, and its role in wound healing remains unclear. Here, we have identified the pivotal role of the α-catenin/FAK/YAP signaling axis in the proliferation and migration of dermal fibroblasts, which contributes to the process of skin wound healing. Briefly, when α-catenin was knocked down specifically in dermal fibroblasts, the wound healing rate is significantly delayed. Moreover, interfering with α-catenin can impede the proliferation and migration of dermal fibroblasts both in vitro and in vivo. Mechanistically, the overexpression of α-catenin upregulates the nuclear accumulation of YAP and transcription of downstream target genes, resulting in enhanced the proliferation and migration of dermal fibroblasts. Furthermore, the FAK Tyr397 phosphorylation inhibitor blocked the promoting effects of α-catenin on YAP activation. Importantly, the continuous phosphorylation mutation of FAK Tyr397 reversed the retardatory effects of α-catenin knockdown on wound healing, by increasing the vitality of fibroblasts. Likewise, α-catenin/FAK was validated as a therapeutic target for wound healing in the db/db chronic trauma model. In summary, our findings have revealed a novel mechanism by which α-catenin facilitates the function of fibroblasts through the activity of the FAK/YAP signaling axis. These findings define a promising therapeutic strategy for accelerating the wound healing process.

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.

A Safe and Efficient Double-Gene-Deleted Live Attenuated Immersion Vaccine to Prevent the Disease Caused by the Infectious Spleen and Kidney Necrosis Virus.

Infectious diseases seriously threaten sustainable aquaculture development, resulting in more than $10 billion in economic losses annually. Immersion vaccines are emerging as the key technology for aquatic disease prevention and control. Here, a safe and efficacious candidate immersion vaccine strain (Δorf103r/tk) of infectious spleen and kidney necrosis virus (ISKNV), in which the orf103r and tk genes were knocked out by homologous recombination, is described. Δorf103r/tk was severely attenuated in mandarin fish (Siniperca chuatsi), inducing mild histological lesions, a mortality rate of only 3%, and eliminated within 21 days. A single Δorf103r/tk immersion-administered dose provided long-lasting protection rates over 95% against lethal ISKNV challenge. Δorf103r/tk also robustly stimulated the innate and adaptive immune responses. For example, interferon expression was significantly upregulated, and the production of specific neutralizing antibodies against ISKNV was markedly induced postimmunization. This work provides proof-of-principle evidence for orf103r- and tk-deficient ISKNV for immersion vaccine development to prevent ISKNV disease in aquaculture production. IMPORTANCE Global aquaculture production reached a record of 122.6 million tons in 2020, with a total value of 281.5 billion U.S. dollars (USD). However, approximately 10% of farmed aquatic animal production is lost due to various infectious diseases, resulting in more than 10 billion USD of economic waste every year. Therefore, the development of vaccines to prevent and control aquatic infectious diseases is of great significance. Infectious spleen and kidney necrosis virus (ISKNV) infection occurs in more than 50 species of freshwater and marine fish and has caused great economic losses to the mandarin fish farming industry in China during the past few decades. Thus, it is listed as a certifiable disease by the World Organization for Animal Health (OIE). Herein, a safe and efficient double-gene-deleted live attenuated immersion vaccine against ISKNV was developed, providing an example for the development of aquatic gene-deleted live attenuated immersion vaccine.

Factors associated with immunological non-response after ART initiation: a retrospective observational cohort study.

BACKGROUND: Among people living with HIV (PLHIV) on antiretroviral therapy (ART), the mortality of immunological non-responders (INRs) is higher than that of immunological responders (IRs). However, factors associated with immunological non-response following ART are not well documented. METHODS: We obtained data for HIV patients from the National Free Antiretroviral Treatment Program database in China. Patients were grouped into IRs (CD4 cell count ≥ 350 cells/µl after 24 months' treatment), immunological incomplete responders (ICRs) (200-350 cells/µl) and INRs (< 200 cells/µl). Multivariable logistic regression was used to assess factors associated with immunological non-response. RESULTS: A total of 3900 PLHIV were included, among whom 2309 (59.2%) were IRs, 1206 (30.9%) ICRs and 385 (9.9%) INRs. In multivariable analysis, immunological non-response was associated with being male (2.07, 1.39-3.09), older age [40-49 years (vs. 18-29 years): 2.05, 1.29-3.25; 50-59 years: 4.04, 2.33-7.00; ≥ 60 years: 5.51, 2.84-10.67], HBV co-infection (1.63, 1.14-2.34), HCV co-infection (2.01, 1.01-4.02), lower CD4 + T cell count [50-200 cells/µl (vs. 200-350 cells/µl): 40.20, 16.83-96.01; < 50 cells/µl: 215.67, 85.62-543.26] and lower CD4/CD8 ratio (2.93, 1.98-4.34) at baseline. Compared with patients treated with non-nucleoside reverse transcriptase inhibitors (NNRTIs) based regimens, those receiving protease inhibitors (PIs) based regimens were less likely to be INRs (0.47, 0.26-0.82). CONCLUSIONS: We found a sizable immunological non-response rate among HIV-infected patients. Being male, older age, coinfection with HBV and HCV, lower CD4 + T cell count and lower CD4/CD8 ratio are risk factors of immunological non-response, whereas PIs-based regimens is a protective factor.

Paraptosis: a non-classical paradigm of cell death for cancer therapy.

Due to the sustained proliferative potential of cancer cells, inducing cell death is a potential strategy for cancer therapy. Paraptosis is a mode of cell death characterized by endoplasmic reticulum (ER) and/or mitochondrial swelling and cytoplasmic vacuolization, which is less investigated. Considerable evidence shows that paraptosis can be triggered by various chemical compounds, particularly in cancer cells, thus highlighting the potential application of this non-classical mode of cell death in cancer therapy. Despite these findings, there remain significant gaps in our understanding of the role of paraptosis in cancer. In this review, we summarize the current knowledge on chemical compound-induced paraptosis. The ER and mitochondria are the two major responding organelles in chemical compound-induced paraptosis, which can be triggered by the reduction of protein degradation, disruption of sulfhydryl homeostasis, overload of mitochondrial Ca2+, and increased generation of reactive oxygen species. We also discuss the stumbling blocks to the development of this field and the direction for further research. The rational use of paraptosis might help us develop a new paradigm for cancer therapy.

Metabolism and the UPR(mt).

During mitochondrial dysfunction or the accumulation of unfolded proteins within mitochondria, cells employ a transcriptional response known as the mitochondrial unfolded protein response (UPR(mt)) to promote cell survival along with the repair and recovery of defective mitochondria. Considerable progress has been made in understanding how cells monitor mitochondrial function and activate the response, as well as in identifying scenarios where the UPR(mt) plays a protective role, such as during bacterial infection, hematopoietic stem cell maintenance, or general aging. To date, much of the focus has been on the role of the UPR(mt) in maintaining or re-establishing protein homeostasis within mitochondria by transcriptionally inducing mitochondrial molecular chaperone and protease genes. In this review, we focus on the metabolic adaptations or rewiring mediated by the UPR(mt) and how this may contribute to the resolution of mitochondrial unfolded protein stress and cell-type-specific physiology.

Biomechanical analysis of miniscrew-assisted molar distalization with clear aligners: a three-dimensional finite element study.

BACKGROUND/OBJECTIVES: To compare the biomechanical characteristics of maxillary molar distalization with clear aligners in conjunction with three types of miniscrew anchorage. MATERIALS/METHODS: Three-dimensional (3D) finite element models of maxillary molar distalization with clear aligners and three types of miniscrew anchorage were established, including (A) control group, (B) direct buccal miniscrew anchorage group, (C) direct palatal miniscrew anchorage group, and (D) indirect buccal miniscrew anchorage group. The 3D displacement of maxillary teeth and the principal stress (maximum tensile and compressive stress) on the root and periodontal ligament (PDL) during molar distalization were recorded. RESULTS: The tooth displacement pattern during maxillary molar distalization in the four groups showed similarities, including labial tipping of anterior teeth, mesial and buccal tipping of premolars, and distal and buccal tipping of molars, but with varying magnitudes. Group C exhibited the greatest molar distalization, with the first molar achieving 0.1334 mm of crown distalization. Group D demonstrated a notable buccal crown movement (0.0682 mm) and intrusion (0.0316 mm) of the first premolar. Compared to Groups A and B, Groups C and D showed less labial crown tipping of the central incisor. Group B showed the greatest amount of maxillary incisor intrusion (central incisor: 0.0145 mm, lateral incisor: 0.0094 mm). Moreover, Groups C and D displayed significantly lower levels of compressive and tensile stress in the roots and PDL of the maxillary central and lateral incisors. LIMITATION: Molar distalization is a dynamic process involving sequential tooth movement stages; however, our research primarily examined the tooth movement patterns in the initial aligner. CONCLUSIONS/IMPLICATIONS: The use of miniscrew anchorage, especially direct palatal miniscrew anchorage, may enhance the treatment efficacy of maxillary molar distalization with clear aligners, leading to increased molar distalization, reduced mesial movement of premolars, and minimized labial tipping of anterior teeth.

Strain-Induced Heteromorphosis Multi-Cavity Cages: Tension-Driven Self-Expansion Strategy for Controllable Enhancement of Complexity in Supramolecular Assembly.

Coordinative supramolecular cages with adjustable cavities have found extensive applications in various fields, but the cavity modification strategies for multi-functional structures are still challenging. Here, we present a tension-driven self-expansion strategy for construction of multi-cavity cages with high structural complexity. Under the regulation of strain-induced capping ligands, unprecedented heteromorphosis triple-cavity cages S2 /S4 were obtained based on a metallo-organic ligand (MOL) scaffold. The heteromorphosis cages exhibited significant higher cavity diversity than the homomorphous double-cavity cages S1 /S3 ; all of the cages were thoroughly characterized through various analytical techniques including (1D and 2D) NMR, ESI-MS, TWIM-MS, AFM, and SAXS analyses. Furthermore, the encapsulation of porphyrin in the cavities of these multi-cavity cages were investigated. This research opens up new possibilities for the architecture of heteromorphosis supramolecular cages via precisely controlled "scaffold-capping" assembly with preorganized ligands, which could have potential applications in the development of multifunctional structures with higher complexity.

The role of non-steroidal anti-inflammatory drugs as adjuncts to periodontal treatment and in periodontal regeneration.

Periodontitis is the sixth most prevalent chronic disease globally and places significant burdens on societies and economies worldwide. Behavioral modification, risk factor control, coupled with cause-related therapy have been the "gold standard" treatment for managing periodontitis. Given that host inflammatory and immunological responses play critical roles in the pathogenesis of periodontitis and impact treatment responses, several adjunctive strategies aimed at modulating host responses and improving the results of periodontal therapy and maintenance have been proposed. Of the many pharmacological host modulators, we focused on non-steroidal anti-inflammatory drugs (NSAIDs), due to their long history and extensive use in relieving inflammation and pain and reducing platelet aggregation. NSAIDs have been routinely indicated for treating rheumatic fever and osteoarthritis and utilized for the prevention of cardiovascular events. Although several efforts have been made to incorporate NSAIDs into the treatment of periodontitis, their effects on periodontal health remain poorly characterized, and concerns over the risk-benefit ratio were also raised. Moreover, there is emerging evidence highlighting the potential of NSAIDs, especially aspirin, for use in periodontal regeneration. This review summarizes and discusses the use of NSAIDs in various aspects of periodontal therapy and regeneration, demonstrating that the benefits of NSAIDs as adjuncts to conventional periodontal therapy remain controversial. More recent evidence suggests a promising role for NSAIDs in periodontal tissue engineering and regeneration.

Altered gut microbiota is associated with different immunologic responses to antiretroviral therapy in HIV-infected men who have sex with men.

The association between gut microbiota and immunologic nonresponse among people living with HIV (PLHIV) on antiretroviral therapy (ART) is not well documented. This study aimed to characterize gut microbiota among HIV-infected men who have sex with men (MSM) with different immunologic responses. We recruited HIV-infected MSM and HIV-uninfected MSM (healthy controls, HC) in Guangzhou, June-October 2021. HIV-infected MSM were grouped into good immunological responders (GIR) (CD4 + T cell count ≥ 350 cells/µL) and poor immunological responders (PIR) (<350 cells/µL). Blood and stool samples were collected. Microbial translocation in serum was performed using enzyme-linked immunosorbent assay (ELISA). Bacterial 16S ribosomal DNA sequencing was performed on stool samples, and microbial metabolites were obtained through gas chromatography-mass spectrometry. 56 GIR, 41 PIR, and 51 HC were included. Microbial translocation marker soluble cluster of differentiation 14 (sCD14) in both GIR and PIR groups was significantly higher than that in HC. Compared with PIR or HC groups, the genera of Coprococcus, Blautia, Clostridium, and SMB53 were decreased, whereas Megamonas and Megasphaera were more abundant in GIR group. Compared with GIR or PIR groups, Bifidobacterium, Collinsella, Faecalibacterium, Oscillospira, and Roseburia were more abundant, whereas Escherichia was decreased in HC group. The levels of benzenoids, imidazoles, phenylpropanoic acids, phenylpropanoids, and pyridines showed strongly significant correlations between differential genera. This study presented a comprehensive landscape of gut microbiota in PLHIV with different treatment outcomes. Megamonas, Coprococcus and Blautia were the major genera correlated with different immunologic responses in PLHIV.

Impact of combination preventative interventions on hospitalization and death under the pandemic of SARS-CoV-2 Omicron variant in China.

With a large population most susceptible to Omicron and emerging SARS-CoV-2 variants, China faces uncertain scenarios if reopening its border. Thus, we aimed to predict the impact of combination preventative interventions on hospitalization and death. An age-stratified susceptible-infectious-quarantined-hospitalized-removed-susceptible (SIQHRS) model based on the new guidelines of COVID-19 diagnosis and treatment (the ninth edition) was constructed to simulate the transmission dynamics of Omicron within 365 days. At baseline, we assumed no interventions other than 60% booster vaccination in individuals aged ≤60 years and 80% in individuals aged >60 years, quarantine and hospitalization. Oral antiviral medications for COVID-19 and nonpharmaceutical interventions (NPIs) such as social distancing and antigen self-testing were considered in subsequent scenarios. Sensitivity analyses were conducted to reflect different levels of interventions. A total of 0.73 billion cumulative quarantines (95% CI 0.53-0.83), 33.59 million hospitalizations (22.41-39.31), and 0.62 million deaths (0.40-0.75) are expected in 365 days. The case fatality rate with pneumonia symptoms (moderate, severe and critical illness) is expected to be 1.83% (1.68-1.99%) and the infected fatality rate is 0.38‰ (0.33-0.4‰). The highest existing hospitalization and ICU occupations are 3.11 (0.30-3.85) and 20.33 (2.01-25.20) times of capacity, respectively. Sensitivity analysis showed that interventions can be adjusted to meet certain conditions to reduce the total number of infections and deaths. In conclusion, after sufficient respiratory and ICU beds are prepared and the relaxed NPIs are in place, the SARS-CoV-2 Omicron variant would not seriously impact the health system.

Changes in HPV prevalence, incidence, and clearance following the use of HIV pre-exposure prophylaxis (PrEP) among MSM in Xinjiang, China: An observational cohort study.

The association between HIV pre-exposure prophylaxis (PrEP) and the natural history of human papillomavirus (HPV) has not been well documented. Our objective was to evaluate the impact of PrEP on the prevalence, incidence, and clearance of anal HPV among men who have sex with men (MSM). Sexually active, HIV-negative MSM aged 18 years and older in Xinjiang, China since September 1, 2016, were enrolled in an ongoing observational cohort study of HPV. At baseline and every 6 months, an anal swab was taken to test for HPV and a questionnaire on sociodemographic characteristics and sexual behaviors was collected. Those who consented to receive PrEP were enrolled in an open-label PrEP intervention study from November 1, 2019, to June 30, 2021. This study analyzed data from participants present in the HPV cohort between November 1, 2019, and June 30, 2021. We compared the prevalence, incidence, and clearance of anal HPV between men who received PrEP (PrEP users) and those who did not (non-PrEP users), and compared men before and after initiating PrEP. We calculated prevalence ratios (PRs), incidence rate ratios (IRRs), and clearance rate ratios (CRRs) for both comparisons. Of the 870 participants present in the HPV cohort during the period between November 1, 2019, and June 30, 2021, 859 had adequate ß-globin for HPV genotype testing and were included in our study. Among them, 429 were PrEP users, while 430 were non-PrEP users. Median age was 32 years (interquartile range [IQR]: 26-38). Among PrEP users, 217 were tested for anal HPV before PrEP initiation. PrEP users had lower prevalence of HPV 45, 51, and 54 (PRs: 0.27 [95% CI: 0.09-0.80], 0.42 [0.21-0.85], and 0.41 [0.17-0.99], respectively) and lower clearance of HPV 16 (CRR: 0.31 [0.10-0.91]) compared with non-PrEP users. PrEP users exhibited lower prevalence of HPV 51 (PR: 0.31 [0.12-0.84]), lower incidence of HPV 6, 11, 16, 39 and 61 (IRRs: 0.34 [0.13-0.90], 0.26 [0.08-0.87], 0.44 [0.21-0.91], 0.21 [0.05-0.93], and 0.19 [0.04-0.82], respectively), as well as higher clearance of HPV 52 (CRR: 2.17 [1.08-4.35]) after PrEP initiation. PrEP use may lower the risk of HPV infection among MSM in Xinjiang, China. Our findings further extend the knowledge of the impact of PrEP on sexually transmitted infections.

Monkeypox awareness and low vaccination hesitancy among men who have sex with men in China.

Men who have sex with men (MSM) have been recommended for targeted monkeypox vaccination. We aimed to investigate monkeypox awareness and explore the correlates of monkeypox vaccination hesitancy among MSM in China. We conducted a cross-sectional survey from August 10 to September 9, 2022. Awareness related to monkeypox and attitude toward monkeypox vaccination among MSM aged ≥18 years were collected. Multivariable logistic regression was applied to evaluate correlates of vaccination hesitancy. The discrepancy in awareness between subgroups regarding HIV status was assessed. A total of 1090 MSM were included (age: median 30 years, interquartile range [IQR], 25-35; HIV-infected: 53.12%). Only 13.85% of respondents expressed high monkeypox vaccination hesitancy. Hesitancy was associated with no fixed income (adjuster odds ratio [aOR], 2.46, 95% confidence interval [CI], 1.48-4.11), infrequent information following (sometimes, 3.01, 1.55-5.83; seldom or never, 5.66, 2.58-12.45), and lack of worries about monkeypox endemic (1.78, 1.11-2.87). Participants who believed that HIV-infected cases accounted for a smaller proportion (1.62, 1.01-2.60), disagreed that monkeypox virus could be detected in semen (2.21, 1.26-3.88), and considered either replication-competent (1.84, 1.14-2.96) or replication-deficient (4.80, 2.26-10.21) monkeypox vaccine unsuitable for HIV-infected people were generally more hesitant. Compared with HIV-uninfected MSM, HIV-infected MSM supported more for vaccination promotion. MSM in China had low hesitancy toward monkeypox vaccination. Safety and affordability of vaccine and availability of information were essential aspects to reduce hesitancy. Education on vaccination benefits should be encouraged to promote future vaccination plans.

Roles of extracellular vesicles on macrophages in inflammatory bone diseases.

Inflammatory bone disease is a general term for a series of diseases caused by chronic inflammation, which leads to the destruction of bone homeostasis, that is, the osteolytic activity of osteoclasts increases, and the osteogenic activity of osteoblasts decreases, leading to osteolysis. Macrophages are innate immune cell with plasticity, and their polarization is related to inflammatory bone diseases. The dynamic balance of macrophages between the M1 phenotype and the M2 phenotype affects the occurrence and development of diseases. In recent years, an increasing number of studies have shown that extracellular vesicles existing in the extracellular environment can act on macrophages, affecting the progress of inflammatory diseases. This process is realized by influencing the physiological activity or functional activity of macrophages, inducing macrophages to secrete cytokines, and playing an anti-inflammatory or pro-inflammatory role. In addition, by modifying and editing extracellular vesicles, the potential of targeting macrophages can be used to provide new ideas for developing new drug carriers for inflammatory bone diseases.

Periodontal ligament cells from patients with treated stable periodontitis: Characterization and osteogenic differentiation potential.

BACKGROUND AND OBJECTIVE: Periodontal ligament progenitor cells (PDL cells) isolated from patients with inflammatory periodontitis have impaired regenerative capacity, but it is unknown whether this capacity can be recovered upon treatment and stabilization of the periodontal condition. The study aimed to investigate the expression of surface markers and the proliferation and osteogenic potential of PDL cells isolated from patients with treated stable periodontitis (S-PDL cells), periodontally healthy individuals (H-PDL cells), and patients with inflammatory periodontitis (I-PDL cells). METHODS: H-PDL, I-PDL, and S-PDL cells were isolated from the extracted teeth of individuals who (1) were periodontally healthy, (2) had inflammatory periodontitis, and (3) had treated stable periodontitis, respectively. The expression levels of surface markers and the proliferative and osteogenic capacities of the PDL cells were assessed. RESULTS: PDL cells derived from all three sources exhibited mesenchymal stem cell (MSC) characteristics. They were positive for MSC-related markers and negative for a hematopoiesis-related marker. However, S-PDL cells had higher proliferation rates, higher expression levels of osteogenic markers, higher alkaline phosphatase activity, and more calcium nodules than I-PDL cells. But all of these parameters remained lower in S-PDL cells than in H-PDL cells. CONCLUSIONS: S-PDL cells proliferated faster and had greater osteogenic potential than I-PDL cells, although these values remained lower than those in H-PDL cells.

Antibiotic resistance in Helicobacter pylori: From potential biomolecular mechanisms to clinical practice.

Increasing rates of Helicobacter pylori resistance are associated with multiple clinical challenges. Bacterial factors linked to H. pylori resistance are mutations, efflux pumps, and biofilms. Gene mutations such as nucleic acid synthesis-related gene mutations, rRNA coding gene mutations, and cell wall synthesis-related gene mutations are the most important mechanisms by which H. pylori evades bactericidal effects. These mechanisms are also closely related to the biological activity of the efflux pump systems and biofilms. Activation of the efflux pump system and biofilm formation both lead to the emergence of MDR strains, further increasing the difficulty of eradication therapy. In this review, the status of antibiotic resistance in H. pylori from different regions and countries is summarized and compared, and H. pylori resistance profiles and their changing trends in the clinic are described. Then, research progress on biomolecular mechanisms underlying antibiotic resistance, diagnostic methods, and treatment strategies are introduced and discussed. Challenges resulting from increasing resistance, potential solutions to combat increasing resistance, and future directions are discussed to help clinicians and researchers better address the emergence and spread of resistant H. pylori strains and optimize drug regimens. With the rate of H. pylori resistance to commonly used antibiotics increasing, more attention should be given to the selection of antibiotics and to monitoring resistance when antibiotics are used for clinical eradication treatment. Individualized precise eradication treatment under the guidance of drug susceptibility testing will become the mainstream method of treatment in the future.

Spatial analysis enables priority selection in conservation practices for landscapes that need ecological security.

Global urbanization has not only promoted social and economic development, but also contributed to seriously ecological challenges. As a type of sustainable landscape patterns, ecological security pattern is considered as an effective spatial pathway to simultaneously conserve ecological security and maintain social-economic development. However, the fragmentation issue of ecological sources of ecological security pattern has not been effectively addressed, although many case studies have been conducted to identify ecological security pattern. In this study, we used spatial conservation prioritization to identify the ecological security pattern of the city belt along the Yellow River in Ningxia, China. Ecological sources were selected using Zonation model while ecological corridors and key ecological nodes were identified with circuit model. The results showed that the ecological security pattern was composed of 97 ecological sources, 226 ecological corridors, 267 pinch points and 22 barriers, covering a total area of 7713.1 km2 and accounting for 34% of the study area. Ecological sources were concentrated in the Helan Mountain, Xiang Mountain and along the Yellow River. Besides, ecological corridors were dense in the southern and eastern part of the study area. Both indicated that the Yellow River and Helan Mountain were the conservation hotspots. Landscape connectivity of ecological sources identified through Zonation-based spatial conservation prioritization was better than that with the scoring approach based on ecosystem service importance. Particularly, in the Zonation approach the landscape connectivity increased with 44% while the average patch area increased with 28% when comparing with the scoring approach. The spatial conservation prioritization approach proposed in this study provides a new effective tool to construct ecological security pattern, which is conducive to the synergic enhancement of landscape connectivity and ecosystem services conservation.