Unveiling the innovative green synthesis mechanism of selenium nanoparticles by exploiting intracellular protein elongation factor Tu from Bacillus paramycoides. / 利用Bacillus paramycoidesç»†èƒžå† è›‹ç™½å»¶ä¼¸å› å­Tu揭示硒纳米颗粒的创新绿色合成机制.

Selenium nanoparticles (SeNPs) have garnered extensive research interest and shown promising applications across diverse fields owing to their distinctive properties, including antioxidant, anticancer, and antibacterial activity (Ojeda et al., 2020; Qu et al., 2023; Zambonino et al., 2021, 2023). Among the various approaches employed for SeNP synthesis, green synthesis has emerged as a noteworthy and eco-friendly methodology. Keshtmand et al. (2023) underscored the significance of green-synthesized SeNPs, presenting a compelling avenue in this domain. This innovative strategy harnesses the potential of natural resources, such as plant extracts or microorganisms, to facilitate the production of SeNPs.

Light-Controlled Bioorthogonal Chemistry Altered Natural Killer Cell Activity for Boosted Adoptive Immunotherapy.

Natural killer (NK) cell-based immunotherapy has received much attention in recent years. However, the practical application is still suffering from the decreased function, inadequate infiltration, and immunosuppressive microenvironment in solid tumor. Herein, we construct the light-responsive porphyrin Fe array-armed NK cells (denoted as NK@p-Fe) for cell behavior modulation via bioorthogonal catalysis. By installing cholesterol-modified porphyrin Fe molecules on NK cell surface, it forms a catalytic array with light-harvesting capabilities. This functionality transforms NK cells into cellular factories, capable of catalyzing the production of active agents in a light-controlled manner. The NK@p-Fe can generate active antineoplastic drug doxorubicin through bioorthogonal reactions to enhance the cytotoxic function of NK cells. Beyond drug synthesis, the NK@p-Fe can also bioorthogonally catalyze to produce FDA approved immune agonist, imiquimod (IMQ). The activated immune agonist plays a dual role by inducing DC maturation for NK cells activation and reshaping tumor immunosuppressive microenvironment for NK cells infiltration. This work represents a paradigm for modulation of adoptive cell behaviors to boost cancer immunotherapy by bioorthogonal catalysis.

Designing intelligent bioorthogonal nanozymes: Recent advances of stimuli-responsive catalytic systems for biomedical applications.

Bioorthogonal nanozymes have emerged as a potent tool in biomedicine due to their unique ability to perform enzymatic reactions that do not interfere with native biochemical processes. The integration of stimuli-responsive mechanisms into these nanozymes has further expanded their potential, allowing for controlled activation and targeted delivery. As such, intelligent bioorthogonal nanozymes have received more and more attention in developing therapeutic approaches. This review provides a comprehensive overview of the recent advances in the development and application of stimuli-responsive bioorthogonal nanozymes. By summarizing the design outlines for anchoring bioorthogonal nanozymes with stimuli-responsive capability, this review seeks to offer valuable insights and guidance for the rational design of these remarkable materials. This review highlights the significant progress made in this exciting field with different types of stimuli and the various applications. Additionally, it also examines the current challenges and limitations in the design, synthesis, and application of these systems, and proposes potential solutions and research directions. This review aims to stimulate further research toward the development of more efficient and versatile stimuli-responsive bioorthogonal nanozymes for biomedical applications.

Surveillance of fluoroquinolones resistance in rifampicin-susceptible tuberculosis in eastern China with whole-genome sequencing-based approach.

Background: Leveraging well-established DNA-level drug resistance mechanisms, whole-genome sequencing (WGS) has emerged as a valuable methodology for predicting drug resistance. As the most effective second-line anti-tuberculosis (anti-TB) drugs, fluoroquinoloness (FQs) are generally used to treat multidrug-resistant tuberculosis (MDR-TB, defined as being resistant to resistant to rifampicin and isoniazid) or rifampicin-resistant tuberculosis (RR-TB). However, FQs are also commonly used in the management of other bacterial infections. There are few published data on the rates of FQs resistance among rifampicin-susceptible TB. The prevalence of FQs resistance among TB patients who are rifampicin-susceptible has not been studied in Zhejiang Province, China. The goal of this study was to provide a baseline characterization of the prevalence of FQs resistance, particularly among rifampicin-susceptible TB in Zhejiang Province, China. Methods: Based on WGS, we have investigated the prevalence of FQs resistance among rifampicin-susceptible TB in Zhejiang Province. All pulmonary TB patients with positive cultures who were identified in Zhejiang area during TB drug resistance surveillance from 2018 to 2019 have enrolled in this population-based retrospective study. Results: The rate of FQs resistance was 4.6% (32/698) among TB, 4.0% (27/676) among rifampicin-susceptible TB, and 22.7% (5/22) among RR-TB. According to WGS, strains that differ within 12 single-nucleotide polymorphisms (SNPs) were considered to be transmission of FQ-resistant strains. Specifically, 3.7% (1/27) of FQs resistance was caused by the transmission of FQs-resistant strains among the rifampicin-susceptible TB and 40.7% (11/27) of FQs resistance was identified as hetero-resistance. Conclusion: The prevalence of FQs resistance among TB patients who were rifampicin-susceptible was severe in Zhejiang. The emergence of FQs resistance in TB isolates that are rifampicin-susceptible was mainly caused by the selection of drug-resistant strains. In order to prevent the emergence of FQs resistance, the WGS-based surveillance system for TB should be urgently established, and clinical awareness of the responsible use of FQs for respiratory infections should be enhanced.

Assessment of phylogenetic relationships and genetic diversity of Sagittaria trifolia using phenotypic traits and SNP markers.

The aquatic perennial herb Sagittaria trifolia L. commonly known as arrowhead, has been utilized in China both as a culinary vegetable and in traditional medicines. Characterizing the phylogenetic relationships and genetic diversity of arrowheads is crucial for improved management, conservation, and efficient utilization of the germplasm resources associated with this species. Herein, we presented the phenotypic traits and genome-wide DNA marker-based analyses of 111 arrowhead accessions, most of which were from China. Cluster analysis revealed that arrowhead could be categorized into two clusters based on 11 phenotypic traits, with Cluster 1 comprising two subclusters. All accessions were clustered into three sub-clusters based primarily on leaf shape and tuber weight. A set of 759,237 high-quality single-nucleotide polymorphisms was identified and used to assess the phylogenetic relationships. Population structure and phylogenetic tree analyses suggested that the accessions could be classified into two major groups, Group I was further subdivided into two subgroups, aligning with the clusters identified through morphological classification. By employing Sagittaria lichuanensis as an outgroup, the rooted tree revealed that the evolutionary relationships within the three groups followed a progression from Group I-1 to Group I-2 and finally to Group II. The landraces were clustered into one group along with the remaining wild accessions. The level of genetic diversity for Group I (π = 0.26) was slightly lower than that which was estimated for Group II (π = 0.29). The lowest pairwise differentiation levels (Fst, 0.008) were obtained from the comparison between groups I-2 and II, indicating that the two groups were the most closely related. This study provides novel insights into germplasm classification, evolutionary relationships, genomics and arrowhead breeding.

Shift in Bacterial Community Structure in the Biodegradation of Benzene and Toluene under Sulfate-Reducing Condition.

Groundwater contaminated by benzene and toluene is a common issue, posing a threat to the ecosystems and human health. The removal of benzene and toluene under sulfate-reducing condition is well known, but how the bacterial community shifts during this process remains unclear. This study aims to evaluate the shift in bacterial community structure during the biodegradation of benzene and toluene under sulfate-reducing condition. In this study, groundwater contaminated with benzene and toluene were collected from the field and used to construct three artificial samples: Control (benzene 50 mg/L, toluene 1.24 mg/L, sulfate 470 mg/L, and HgCl2 250 mg/L), S1 (benzene 50 mg/L, toluene 1.24 mg/L, sulfate 470 mg/L), and S2 (benzene 100 mg/L, toluene 2.5 mg/L, sulfate 940 mg/L). The contaminants (benzene and toluene), geochemical parameters (sulfate, ORP, and pH), and bacterial community structure in the artificial samples were monitored over time. By the end of this study (day 90), approximately 99% of benzene and 96% of toluene could be eliminated in both S1 and S2 artificial samples, while in the Control artificial sample the contaminant levels remained unchanged due to microbial inactivation. The richness of bacterial communities initially decreased but subsequently increased over time in both S1 and S2 artificial samples. Under sulfate-reducing condition, key players in benzene and toluene degradation were identified as Pseudomonas, Janthinobacterium, Novosphingobium, Staphylococcus, and Bradyrhizobium. The results could provide scientific basis for remediation and risk management strategies at the benzene and toluene contaminated sites.

Remediation of petroleum-contaminated site soil by bioaugmentation with immobilized bacterial pellets stimulated by a controlled-release oxygen composite.

Bioaugmentation techniques still show drawbacks in the cleanup of total petroleum hydrocarbons (TPHs) from petroleum-contaminated site soil. Herein, this study explored high-performance immobilized bacterial pellets (IBPs) embed Microbacterium oxydans with a high degrading capacity, and developed a controlled-release oxygen composite (CROC) that allows the efficient, long-term release of oxygen. Tests with four different microcosm incubations were performed to assess the effects of IBPs and CROC on the removal of TPHs from petroleum-contaminated site soil. The results showed that the addition of IBPs and/or CROC could significantly promote the remediation of TPHs in soil. A CROC only played a significant role in the degradation of TPHs in deep soil. The combined application of IBPs and CROC had the best effect on the remediation of deep soil, and the removal rate of TPHs reached 70%, which was much higher than that of nature attenuation (13.2%) and IBPs (43.0%) or CROC (31.9%) alone. In particular, the CROC could better promote the degradation of heavy distillate hydrocarbons (HFAs) in deep soil, and the degradation rates of HFAs increased from 6.6% to 33.2%-21.0% and 67.9%, respectively. In addition, the IBPs and CROC significantly enhanced the activity of dehydrogenase, catalase, and lipase in soil. Results of the enzyme activity were the same as that of TPH degradation. The combined application of IBPs and CROC not only increased the microbial abundance and diversity of soil, but also significantly enhanced the enrichment of potential TPH-biodegrading bacteria. M. oxydans was dominant in AP (bioaugmentation with addition of IBPs) and APO (bioaugmentation with the addition of IBPs and CROC) microcosms that added IBPs. Overall, the IBPs and CROC developed in this study provide a novel option for the combination of bioaugmentation and biostimulation for remediating organic pollutants in soil.

Genomic and spatial analysis reveal the transmission dynamics of tuberculosis in areas with high incidence of Zhejiang, China: A prospective cohort study.

In the mountainous, rural regions of eastern China, tuberculosis (TB) remains a formidable challenge; however, the long-term molecular epidemiological surveillance in these regions is limited. This study aimed to investigate molecular and spatial epidemiology of TB in two mountainous, rural counties of Zhejiang Province, China, from 2015 to 2021, to elucidate the recent transmission and drug-resistance profiles. The predominant Lineage 2 (L2) Beijing family accounted for 80.1% of total 532 sequenced Mycobacterium tuberculosis (Mtb) strains, showing consistent prevalence over seven years. Gene mutations associated with drug resistance were identified in 19.4% (103/532) of strains, including 47 rifampicin or isoniazid-resistant strains, eight multi-drug-resistant (MDR) strains, and five pre-extensively drug-resistant (pre-XDR) strains. Genomic clustering revealed 53 distinct clusters with an overall transmission clustering rate of 23.9% (127/532). Patients with a history of retreatment and those infected with L2 strains had a higher risk of recent transmission. Spatial and epidemiological analysis unveiled significant transmission hotspots, especially in densely populated urban areas, involving various public places such as medical institutions, farmlands, markets, and cardrooms. The study emphasizes the pivotal role of Beijing strains and urban-based TB transmission in the western mountainous regions in Zhejiang, highlighting the urgent requirement for specific interventions to mitigate the impact of TB in these unique communities.

Accelerating diabetic wound healing by ROS-scavenging lipid nanoparticle-mRNA formulation.

Current treatment options for diabetic wounds face challenges due to low efficacy, as well as potential side effects and the necessity for repetitive treatments. To address these issues, we report a formulation utilizing trisulfide-derived lipid nanoparticle (TS LNP)-mRNA therapy to accelerate diabetic wound healing by repairing and reprogramming the microenvironment of the wounds. A library of reactive oxygen species (ROS)-responsive TS LNPs was designed and developed to encapsulate interleukin-4 (IL4) mRNA. TS2-IL4 LNP-mRNA effectively scavenges excess ROS at the wound site and induces the expression of IL4 in macrophages, promoting the polarization from the proinflammatory M1 to the anti-inflammatory M2 phenotype at the wound site. In a diabetic wound model of db/db mice, treatment with this formulation significantly accelerates wound healing by enhancing the formation of an intact epidermis, angiogenesis, and myofibroblasts. Overall, this TS LNP-mRNA platform not only provides a safe, effective, and convenient therapeutic strategy for diabetic wound healing but also holds great potential for clinical translation in both acute and chronic wound care.

A Manganese-Based Nanodriver Coordinates Tumor Prevention and Suppression through STING Activation in Glioblastoma.

Glioblastoma (GBM), the most prevalent and aggressive primary malignant brain tumor, exhibits profound immunosuppression and demonstrates a low response rate to current immunotherapy strategies. Manganese cations (Mn2+) directly activate the cGAS/STING pathway and induce the unique catalytic synthesis of 2'3'-cGAMP to facilitate type I IFN production, thereby enhancing innate immunity. Here, a telodendrimer and Mn2+-based nanodriver (PLHM) with a small size is developed, which effectively target lymph nodes through the blood circulation and exhibit tumor-preventive effects at low doses of Mn2+ (3.7 mg kg-1). On the other hand, the PLHM nanodriver also exhibits apparent antitumor effects in GBM-bearing mice via inducing in vivo innate immune responses. The combination of PLHM with doxorubicin nanoparticles (PLHM-DOX NPs) results in superior inhibition of tumor growth in GBM-bearing mice due to the synergistic potentiation of STING pathway functionality by Mn2+ and the presence of cytoplasmic DNA. These findings demonstrate that PLHM-DOX NPs effectively stimulate innate immunity, promote dendritic cell maturation, and orchestrate cascaded infiltration of CD8 cytotoxic T lymphocytes within glioblastomas characterized by low immunogenicity. These nanodivers chelated with Mn2+ show promising potential for tumor prevention and antitumor effects on glioblastoma by activating the STING pathway.

Single-Atom Catalysts Mediated Bioorthogonal Modulation of N6-Methyladenosine Methylation for Boosting Cancer Immunotherapy.

Bioorthogonal reactions provide a powerful tool to manipulate biological processes in their native environment. However, the transition-metal catalysts (TMCs) for bioorthogonal catalysis are limited to low atomic utilization and moderate catalytic efficiency, resulting in unsatisfactory performance in a complex physiological environment. Herein, sulfur-doped Fe single-atom catalysts with atomically dispersed and uniform active sites are fabricated to serve as potent bioorthogonal catalysts (denoted as Fe-SA), which provide a powerful tool for in situ manipulation of cellular biological processes. As a proof of concept, the N6-methyladensoine (m6A) methylation in macrophages is selectively regulated by the mannose-modified Fe-SA nanocatalysts (denoted as Fe-SA@Man NCs) for potent cancer immunotherapy. Particularly, the agonist prodrug of m6A writer METTL3/14 complex protein (pro-MPCH) can be activated in situ by tumor-associated macrophage (TAM)-targeting Fe-SA@Man, which can upregulate METTL3/14 complex protein expression and then reprogram TAMs for tumor killing by hypermethylation of m6A modification. Additionally, we find the NCs exhibit an oxidase (OXD)-like activity that further boosts the upregulation of m6A methylation and the polarization of macrophages via producing reactive oxygen species (ROS). Ultimately, the reprogrammed M1 macrophages can elicit immune responses and inhibit tumor proliferation. Our study not only sheds light on the design of single-atom catalysts for potent bioorthogonal catalysis but also provides new insights into the spatiotemporal modulation of m6A RNA methylation for the treatment of various diseases.

Transmission dynamics of drug-resistant tuberculosis in Ningbo, China: an epidemiological and genomic analysis.

Background: Tuberculosis (TB), particularly drug-resistant TB (DR-TB), remains a significant public health concern in Ningbo, China. Understanding its molecular epidemiology and spatial distribution is paramount for effective control. Methods: From December 24, 2020, to March 12, 2023, we collected clinical Mycobacterium tuberculosis (MTB) strains in Ningbo, with whole-genome sequencing performed on 130 MTB strains. We analyzed DR-related gene mutations, conducted phylogenetic and phylodynamic analyses, identified recent transmission clusters, and assessed spatial distribution. Results: Among 130 DR-TB cases, 41% were MDR-TB, 36% pre-XDR-TB, 19% RR-TB, and 3% HR-TB. The phylogenetic tree showed that 90% of strains were Lineage 2 (Beijing genotype), while remaining 10% were Lineage 4 (Euro-American genotype). The spatial analysis identified hotspots of DR-TB in Ningbo's northern region, particularly in traditional urban centers. 31 (24%) of the DR-TB cases were grouped into 7 recent transmission clusters with a large outbreak cluster containing 15 pre-XDR-TB patients. Epidemiological analyses suggested a higher risk of recent DR-TB transmission among young adult patients who frequently visited Internet cafes, game rooms, and factories. Conclusion: Our study provides comprehensive insights into the epidemiology and genetics of DR-TB in Ningbo. The presence of genomic clusters highlights recent transmission events, indicating the need for targeted interventions. These findings are vital for informing TB control strategies in Ningbo and similar settings.

Evaluation of nucleotide MALDI-TOF-MS for the identification of Mycobacterium species.

Background: The accurate identification of the Mycobacterium tuberculosis complex (MTBC) and different nontuberculous mycobacteria (NTM) species is crucial for the timely diagnosis of NTM infections and for reducing poor prognoses. Nucleotide matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) has been extensively used for microbial identification with high accuracy and throughput. However, its efficacy for Mycobacterium species identification has been less studied. The objective of this study was to evaluate the performance of nucleotide MALDI-TOF-MS for Mycobacterium species identification. Methods: A total of 933 clinical Mycobacterium isolates were preliminarily identified as NTM by the MPB64 test. These isolates were identified by nucleotide MALDI-TOF-MS and Sanger sequencing. The performance of nucleotide MALDI-TOF MS for identifying various Mycobacterium species was analyzed based on Sanger sequencing as the gold standard. Results: The total correct detection rate of all 933 clinical Mycobacterium isolates using nucleotide MALDI-TOF-MS was 91.64% (855/933), and mixed infections were detected in 18.65% (174/933) of the samples. The correct detection rates for Mycobacterium intracellulare, Mycobacterium abscessus, Mycobacterium kansasii, Mycobacterium avium, MTBC, Mycobacterium gordonae, and Mycobacterium massiliense were 99.32% (585/589), 100% (86/86), 98.46% (64/65), 94.59% (35/37), 100.00% (34/34), 95.65% (22/23), and 100% (19/19), respectively. For the identification of the MTBC, M. intracellulare, M. abscessus, M. kansasii, M. avium, M. gordonae, and M. massiliense, nucleotide MALDI-TOF-MS and Sanger sequencing results were in good agreement (k > 0.7). Conclusion: In conclusion, nucleotide MALDI-TOF-MS is a promising approach for identifying MTBC and the most common clinical NTM species.

Study on the Wettability Alteration of Tight Sandstone by Low-Frequency Vibration and Nanofluid.

The efficiency of reservoir imbibition in continental tight sandstone reservoirs is severely hindered due to their intricate wettability characteristics. To address this challenge, we propose a novel synergistic approach that combines low-frequency vibration and nanofluid treatment. This method integrates physical shear and chemical wettability alteration to effectively modify the wettability of neutral oil-wet tight sandstone, thereby enhancing the imbibition process. In this study, we formulated a TX-100 nanofluid system through physical modification. By utilizing the contact angle as a benchmark for evaluation, we investigated the impact of low-frequency fluctuations on the wettability of oil-wet sandstone. Subsequently, we identified the optimal combination of wave parameters. Through isothermal adsorption experiments and mechanical analyses of oil droplets subjected to fluctuations, we systematically elucidated the mechanism by which fluctuations collaborate with nanofluids to alter the wettability of oil-wet sandstone. Furthermore, we evaluated the oil displacement efficiency of cores subjected to the combined action of low-frequency fluctuations and nanofluid treatment. Our findings revealed that the TX-100 nanofluid reduced the static contact angle of oil-wet sandstone by 58%. When assisted by the optimal fluctuation parameters, the nanofluid treatment contributed to a 64% reduction in the contact angle of strongly oil-wet sandstone. This effect further amplified the reversal of wettability in oil-wet sandstone. Through the application of various wave-assisted treatment agents, the efficiency of oil removal was increased by a minimum of 16%. Moreover, the recovery degree of wave-assisted nanofluid imbibition experienced a remarkable enhancement of 30.39%. Nuclear magnetic resonance analysis demonstrated a significant improvement in pore sizes smaller than 1 µm as a result of the composite process.

Associations of genetic variants within TYK2 with pulmonary tuberculosis among Chinese population.

BACKGROUND: Pulmonary tuberculosis (PTB) is a common infectious disease caused by mycobacterium tuberculosis (MTB) and the present study aims to explore the associations of genetic variants within tyrosine kinases 2 (TYK2) with PTB incidence. METHODS: A population-based case control study including 168 smear-positive PTB cases and 251 controls was conducted. Five single nucleotide polymorphisms (SNPs) including rs280520, rs91755, rs2304256, rs12720270, rs280519 located within TYK2 gene were selected and MassARRAY® MALDI-TOF system was employed for genotyping. SPSS 19.0 was adopted for statistical analysis, non-conditional logistic regression was conducted. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were computed to estimate their contributions to PTB incidence. RESULTS: In the overall study population, rs91755 TT and rs280519 AA genotypes were found to be associated with reduced PTB risk (OR = 0.34, 95% CI: 0.16-0.72; OR = 0.38, 95% CI: 0.18-0.79, respectively). After stratification for sex, we found that among the male population, rs91755TG/TT, rs12720270AG/GG and rs280519AG/AA genotypes were associated with reduced PTB risk (OR = 0.41, 95% CI: 0.21-0.80; OR = 0.44, 95% CI: 0.21-0.94; OR = 0.42, 95% CI: 0.21-0.82, respectively). After stratification for age, we found that among those aged <60 years, rs91755TT and rs280519AA genotype were associated with reduced PTB risk (OR = 0.29, 95% CI: 0.09-0.90; OR = 0.34, 95% CI: 0.11-1.08, respectively); while rs2304256AC/AA genotype was associated with increased PTB risk (OR = 2.68, 95% CI: 1.05-6.85). Haplotype analysis revealed that AGAAG and ATCGA (Combined with rs280520, rs91755, rs2304256, rs12720270 and rs280519) were associated with increased (OR = 1.54, 95% CI: 1.01-2.37) and decreased PTB risk (OR = 0.70, 95% CI: 0.52-0.94), respectively. CONCLUSIONS: The genetic variants located within TYK2 including rs91755, rs12720270 and rs280519 were found to be associated with modified PTB risk and the SNPs had potential to be the biomarkers to predict PTB incidence risk.

In Vitro Detection of S100B and Severity Evaluation of Traumatic Brain Injury Based on Biomimetic Peptide-Modified Nanochannels.

The diagnosis and evaluation of traumatic brain injury (TBI) are crucial steps toward the treatment and prognosis of patients. A common question remains as to whether it is possible to introduce an ideal device for signal detection and evaluation that can directly connect digital signals with TBI, thereby enabling prompt response of the evaluation signal and sensitive and specific functioning of the detection process. Herein, a method is presented utilizing polymetric porous membranes with TRTK-12 peptide-modified nanochannels for the detection of S100B (a TBI biomarker) and assessment of TBI severity. The method leverages the specific bonding force between TRTK-12 peptide and S100B protein, along with the nanoconfinement effect of nanochannels, to achieve high sensitivity (LOD: 0.002 ng mL-1) and specificity (∆I/I0: 44.7%), utilizing ionic current change as an indicator. The proposed method, which is both sensitive and specific, offers a simple yet responsive approach for real-time evaluation of TBI severity. This innovative technique provides valuable scientific insights into the advancement of future diagnostic and therapeutic integration devices.

Facile green synthesis of wasted hop-based zinc oxide nanozymes as peroxidase-like catalysts for colorimetric analysis.

Hops are a common ingredient in beer production, and a considerable quantity of hops is usually discarded as a waste material once the brewing process is completed. Transforming this waste material into valuable nanomaterials offers a sustainable approach that has the potential to significantly mitigate environmental impact. Herein, a facile and green protocol for the production of zinc oxide nanozymes (ZnO NZs) using wasted hop extract (WHE) as a natural precursor was demonstrated. The process involved a hydrothermal synthesis method followed by a calcination step to form the final ZnO NZs. The results revealed that lupulon, the main ß-acid in hops, particularly the phenolic hydroxy group, is primarily responsible for the biosynthesis of ZnO NZs. The WHE-ZnO NZs exhibited exceptional peroxidase-like (POD-like) activity and served as effective catalysts for the oxidation of 3,3,5,5-tetramethylbenzidine (TMB) in the presence of hydrogen peroxide (H2O2). Analysis of the catalytic mechanism revealed that the POD-like activity of these WHE-ZnO NZs originated from their ability to expedite the transfer of electrons between TMB and H2O2, resulting in the enzymatic kinetics following the standard Michaelis-Menten mechanism. Furthermore, we developed a straightforward and user-friendly colorimetric technique for detecting both H2O2 and glucose. By utilizing the WHE-ZnO NZs as POD-like catalysts, we achieved a linear detection range of 1-1000 µM and a limit of detection of 0.24 µM (S/N = 3) for H2O2 detection and a linear range of 0-100 mM and a detection limit of 16.73 µM (S/N = 3) for glucose detection. These results highlighted the potential applications of our waste-to-resource approach for nanozyme synthesis in the field of analytical chemistry.

Bedaquiline Resistance and Molecular Characterization of Rifampicin-Resistant Mycobacterium Tuberculosis Isolates in Zhejiang, China.

Purpose: This study aimed to determine the prevalence and molecular characterization of bedaquiline (BDQ) resistance among rifampicin-resistant tuberculosis (RR-TB) isolates collected from Zhejiang, China. Patients and Methods: A total of 245 RR-TB isolates were collected from 19 municipal TB hospitals in Zhejiang province, China between January and December 2021. Microplate assays were used to determine the minimum inhibitory concentrations (MIC) of BDQ. Whole-genome sequencing (WGS) was performed on isolates with MIC values for BDQ ≥ 0.25 µg/mL. Results: Five (2.04%) BDQ-resistant strains were isolated from 245 tuberculosis patients. The resistance rate of BDQ was not correlated to the sex, age, treatment history, or occupation of patients. Four BDQ-resistant isolates and three BDQ-sensitive isolates were found to carry Rv0678 mutations, and one BDQ-resistant strain carried both Rv0678 and pepQ mutations. No mutations within the atpE and Rv1979c genes were observed. Conclusion: BDQ demonstrated strong in vitro antibacterial activity against RR-TB isolates, and the Rv0678 gene was identified as the primary mechanism contributing to BDQ resistance among RR-TB isolates from Zhejiang, China. Furthermore, in addition to the four currently known resistance-associated genes (atpE, Rv0678, Rv1979c, and pepQ), other mechanisms of resistance to BDQ may exist that need further study.

Targeting Kindlin-2 in adipocytes increases bone mass through inhibiting FAS/PPARγ/FABP4 signaling in mice.

Osteoporosis (OP) is a systemic skeletal disease that primarily affects the elderly population, which greatly increases the risk of fractures. Here we report that Kindlin-2 expression in adipose tissue increases during aging and high-fat diet fed and is accompanied by decreased bone mass. Kindlin-2 specific deletion (K2KO) controlled by Adipoq-Cre mice or adipose tissue-targeting AAV (AAV-Rec2-CasRx-sgK2) significantly increases bone mass. Mechanistically, Kindlin-2 promotes peroxisome proliferator-activated receptor gamma (PPARγ) activation and downstream fatty acid binding protein 4 (FABP4) expression through stabilizing fatty acid synthase (FAS), and increased FABP4 inhibits insulin expression and decreases bone mass. Kindlin-2 inhibition results in accelerated FAS degradation, decreased PPARγ activation and FABP4 expression, and therefore increased insulin expression and bone mass. Interestingly, we find that FABP4 is increased while insulin is decreased in serum of OP patients. Increased FABP4 expression through PPARγ activation by rosiglitazone reverses the high bone mass phenotype of K2KO mice. Inhibition of FAS by C75 phenocopies the high bone mass phenotype of K2KO mice. Collectively, our study establishes a novel Kindlin-2/FAS/PPARγ/FABP4/insulin axis in adipose tissue modulating bone mass and strongly indicates that FAS and Kindlin-2 are new potential targets and C75 or AAV-Rec2-CasRx-sgK2 treatment are potential strategies for OP treatment.

Trend of the Tuberculous Pleurisy Notification Rate in Eastern China During 2017-2021: Spatiotemporal Analysis.

BACKGROUND: Tuberculous pleurisy (TP) presents a serious allergic reaction in the pleura caused by Mycobacterium tuberculosis; however, few studies have described its spatial epidemiological characteristics in eastern China. OBJECTIVE: This study aimed to determine the epidemiological distribution of TP and predict its further development in Zhejiang Province. METHODS: Data on all notified cases of TP in Zhejiang Province, China, from 2017 to 2021 were collected from the existing tuberculosis information management system. Analyses, including spatial autocorrelation and spatial-temporal scan analysis, were performed to identify hot spots and clusters, respectively. The prediction of TP prevalence was performed using the seasonal autoregressive integrated moving average (SARIMA), Holt-Winters exponential smoothing, and Prophet models using R (The R Foundation) and Python (Python Software Foundation). RESULTS: The average notification rate of TP in Zhejiang Province was 7.06 cases per 100,000 population, peaking in the summer. The male-to-female ratio was 2.18:1. In terms of geographical distribution, clusters of cases were observed in the western part of Zhejiang Province, including parts of Hangzhou, Quzhou, Jinhua, Lishui, Wenzhou, and Taizhou city. Spatial-temporal analysis identified 1 most likely cluster and 4 secondary clusters. The Holt-Winters model outperformed the SARIMA and Prophet models in predicting the trend in TP prevalence. CONCLUSIONS: The western region of Zhejiang Province had the highest risk of TP. Comprehensive interventions, such as chest x-ray screening and symptom screening, should be reinforced to improve early identification. Additionally, a more systematic assessment of the prevalence trend of TP should include more predictors.