Nitroreductase-Responsive Photosensitizers for Selective Imaging and Photo-Inactivation of Intracellular Bacteria.

Intracellular Staphylococcus aureus (S. aureus), especially the methicillin resistant staphylococcus aureus (MRSA), are difficult to detect and eradicate due to the protection by the host cells. Antibacterial photodynamic therapy (aPDT) offers promise in treating intracellular bacteria, provided that selective damage to the bacteria ranther than host cells can be realized. According to the different nitroreductase (NTR) levels in mammalian cells and S. aureus, herein NTR-responsive photosensitizers (PSs) (T)CyI-NO2 were designed and synthesized. The emission and 1O2 generation of (T)CyI-NO2 are quenched by the 4-nitrobenzyl group, but can be specifically switched on by bacterial NTR. Therefore, selective imaging and photo-inactivation of intracellular S. aureus and MRSA were achieved. Our findings may pave the way for the development of more efficient and selective aPDT agents to combat intractable intracellular infections.

Quantitative analysis of mRNA-lipid nanoparticle stability in human plasma and serum by size-exclusion chromatography coupled with dual-angle light scattering.

Understanding the stability of mRNA loaded lipid nanoparticles (mRNA-LNPs) is imperative for their clinical development. Herein, we propose the use of size-exclusion chromatography coupled with dual-angle light scattering (SEC-MALS) as a new approach to assessing mRNA-LNP stability in pure human serum and plasma. By applying a dual-column configuration to attenuate interference from plasma components, SEC-MALS was able to elucidate the degradation kinetics and physical property changes of mRNA-LNPs, which have not been observed accurately by conventional dynamic light scattering techniques. Interestingly, both serum and plasma had significantly different impacts on the molecular weight and radius of gyration of mRNA-LNPs, suggesting the involvement of clotting factors in desorption of lipids from mRNA-LNPs. We also discovered that a trace impurity (~1 %) in ALC-0315, identified as its O-tert-butyloxycarbonyl-protected form, greatly diminished mRNA-LNP stability in serum. These results demonstrated the potential utility of SEC-MALS for optimization and quality control of LNP formulations.

An Alkynyl-Dangling Ru(II) Polypyridine Complex for Targeted Antimicrobial Photodynamic Therapy.

To realize clinical application of antibacterial photodynamic therapy (aPDT), one of the most arduous challenges is how to render aPDT agents high selectivity against bacterial pathogens. In light of the fact that amino group-containing lipids are rich on the outer surfaces of Gram-positive bacteria, we herein constructed an alkynyl-dangling ruthenium(II) polypyridine complex (Ru2) to preferentially label Staphylococcus aureus (S. aureus) and methicillin-resistant Staphylococcus aureus (MRSA) over mammalian cells via the amino-yne bio-orthogonal click reaction. Thanks to the strong singlet oxygen generation ability, Ru2 could photo-inactivate S. aureus and MRSA effectively and specifically. Phosphatidylethanolamine (PE) molecules also exist in mammalian cells but are not accessible for Ru2, leading to its poor binding/uptake and negligible cytotoxicity in the dark and upon irradiation towards mammalian cells as well as low hemolysis, all favorable for aPDT application.

Sugar-Assisted Cryopreservation of Stem Cell-Laden Gellan Gum-Collagen Interpenetrating Network Hydrogels.

Tissue engineering involves the transplantation of stem cell-laden hydrogels as synthetic constructs to replace damaged tissues. However, their time-consuming fabrication procedures are hurdles to widespread application in clinics. Fortunately, similar to cell banking, synthetic tissues could be cryopreserved for subsequent central distribution. Here, we report the use of trehalose and gellan gum as biomacromolecules to form a cryopreservable yet directly implantable hydrogel system for adipose-derived stem cell (ADSC) delivery. Through a modified cell encapsulation method and a preincubation step, adequate cryoprotection was afforded at 0.75 M trehalose to the encapsulated ADSCs. At this concentration, trehalose demonstrated lower propensity to induce apoptosis than 10% DMSO, the current gold standard cryoprotectant. Moreover, when cultured along with trehalose after thawing, the encapsulated ADSCs retained their stem cell-like phenotype and osteogenic differentiation capacity. Taken together, this study demonstrates the feasibility of an "off-the-shelf" biomacromolecule-based synthetic tissue to be applied in widespread tissue engineering applications.

Distinct diagnostic and prognostic values of Glypicans gene expression in patients with hepatocellular carcinoma.

BACKGROUD: In our current work, we aimed to investigate the expressions of glypican (GPC) family genes at the mRNA level and assess their prognostic significances in patients with hepatocellular carcinoma (HCC). METHODS: The pathological roles of GPC family genes were examined using bioinformatics analysis. The diagnostic values of GPC genes were explored with the Gene Expression Profiling Interactive Analysis. Moreover, the mRNA expression and prognostic values of GPC genes were assessed via the KM plotter database. RESULTS: Our data showed that the expression of GPC-3 was dramatically increased in the liver tumor tissue. Moreover, the expressions of the other five GPC family members were not significantly different between the tumor and normal liver tissues (P > 0.05). Furthermore, the up-regulation of GPC-1 at the mRNA level was dramatically correlated to the reduced overall survival (OS) for all HCC patients (hazard ratio = 2.03, 95% confidence intervals =1.44-2.87, P = 4.1e-05) compared with its low-expression group. Besides, the prognosis of the Caucasians was related to most GPC family genes, while the prognosis of the Asian race was only related to the expression of GPC-2. Besides, for pathological factors, including stage, grade, AJCC, and vascular invasion, the higher the pathological grade and vascular invasiveness, the lower the expression levels of GPC family genes (P < 0.05). Finally, the expression levels of GPC-1, 2, and 3 in the hepatitis group were related to the poor prognosis of HCC in the risk factor (alcohol consumption and hepatitis) subgroup (P < 0.05). CONCLUSIONS: Our findings indicated that GPC-3 was dysregulated in HCC compared with paracancerous tissues. The expression of GPC-1 could be used as a potent predictive index for the general prognosis of HCC. The pathology, patients, and risk factors might affect the prognostic value of GPC family genes in HCC.

Factors associated with diagnostic accuracy, technical success and adverse events of endoscopic ultrasound-guided fine-needle biopsy: A systematic review and meta-analysis.

BACKGROUND AND AIM: Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) is used to diagnose lesions within or adjacent to the digestive tract. However, there is no report on the overall diagnostic accuracy, technical success, and adverse events of FNB. The aims of this study were to conduct a systematic review and meta-analysis to comprehensively assess the diagnostic accuracy, technical success, and adverse events of FNB. METHODS: Pubmed, Embase, and Cochrane Library databases were searched for relevant articles published in English from January 1998 to May 2019 (No. CRD42019141647). Primary outcomes were EUS-FNB related diagnostic accuracy rate, technical success rate, and adverse event rate. RESULTS: A total of 51 articles including 5330 patients met our criteria. The overall EUS-FNB related diagnostic accuracy rate, technical success rate, and adverse event rate was 90.82% [95% confidence interval (CI) 88.69-92.76%], 99.71% [95% CI 99.35-99.93%], and 0.59% [95% CI 0.29-1.0%], respectively. Biopsy with 22G needle could increase the diagnostic accuracy rate and technical success rate to 92.17% [95% CI 89.32-94.61%] and 99.88% [95% CI 99.64-99.99%], respectively, and decrease the adverse event to 0.37% [95% CI 0.08-0.87%]. Moreover, it showed that 22G needle was an independent factor associated with a higher diagnostic accuracy rate and technical success rate and a lower adverse event rate (P = 0.04, P < 0.001, and P = 0.04, respectively) by univariate and multivariate meta-regression analyses. CONCLUSION: Endoscopic ultrasound-guided fine-needle biopsy is a feasible and safe procedure for lesions within or adjacent to the digestive tract. Biopsy using 22G needle could increase the diagnostic accuracy rate and technical success rate and decrease adverse event rate during the FNB procedure.

Contrast-enhanced transrectal ultrasound can reduce collection of unnecessary biopsies when diagnosing prostate cancer and is predictive of biochemical recurrence following a radical prostatectomy in patients with localized prostate cancer.

BACKGROUND: To investigate the value of using contrast-enhanced transrectal ultrasound (CETRUS) to reduce unnecessary collection of biopsies during prostate cancer diagnosis and its utility in predicting biochemical recurrence in patients with localized prostate cancer. METHODS: This was a prospective study of suspected prostate cancer patients who were evaluated with CETRUS followed by a prostate biopsy. Prostate blood flow via CETRUS was graded using a 5-point scale. The relationship between CETRUS score and biopsy outcome was then analyzed for all patients; univariate and multi-variate analyses were used to determine the probable prognostic factors for biochemical recurrence in patients with localized prostate cancer that underwent a radical prostatectomy. RESULTS: A total of 347 patients were enrolled in the study. Prostate cancer was found in 164 patients. A significant positive correlation (r = 0.69, p < 0.001) was found between CETRUS scores and prostate cancer incidence. Using CETRUS scores ≥2 as the threshold for when to biopsy could have safely reduced the number of biopsies taken overall by 12.1% (42/347) and spared 23.0% (42/183) of patients from undergoing an unnecessary biopsy. 77 patients with localized prostate cancer underwent a radical prostatectomy. The median follow-up time was 30 months (range: 8-56 months) and 17 of these 77 patients exhibited biochemical recurrence during the follow-up period. 3-year biochemical recurrence-free survival rates were 86% for patients with low CETRUS scores (≤ 3) and 59% for patients with high scores (> 3; p = 0.015). Multivariate Cox regression analysis indicated that CETRUS score was an independent predictor of biochemical recurrence (HR: 7.02; 95% CI: 2.00-24.69; p = 0.002). CONCLUSIONS: CETRUS scores may be a useful tool for reducing the collection unnecessary biopsy samples during prostate cancer diagnosis and are predictive of biochemical recurrence in patients with localized prostate cancer following a radical prostatectomy.

NF45 promotes esophageal squamous carcinoma cell invasion by increasing Rac1 activity through 14-3-3ε protein.

Nuclear factor 45 (NF-45) has been found to be markedly upregulated in several cancers, including esophageal squamous cell carcinoma (ESCC). However, the molecular mechanisms underlying its functions remain unclear. In this study, we confirm that overexpression of NF45 was frequently detected in ESCC tissues and was associated with poor outcome. Overexpression studies revealed that NF-45 promoted cell growth and invasion and upregulated Rac1/Tiam1 signalling via 14-3-3ε protein in ESCC cell lines. This novel mechanism linking upregulated NF45 expression to increased 14-3-3ε/Rac1/Tiam1 signalling and subsequent growth and invasion in ESCC may aid in identification of new therapeutic targets for this disease.

Endocut Versus Conventional Blended Electrosurgical Current for Endoscopic Biliary Sphincterotomy: A Meta-Analysis of Complications.

BACKGROUND AND AIMS: Endoscopic biliary sphincterotomy (EST) is commonly performed during therapeutic endoscopic retrograde cholangiopancreatography (ERCP), but is an independent risk factor for post-ERCP pancreatitis, bleeding and duodenal perforation. These are partly ascribed to the electrosurgical current mode used for EST, and currently the optimal current model for EST remains controversial. In this study, we aimed to compare the rate of complications undergoing EST using the Endocut versus the blended current. METHODS: A systematic search of databases was performed for relevant published and prospective studies including randomized clinical trials (RCTs) to compare Endocut with blended current modes for EST. Data were collected from inception until 1 July 2018, using post-ERCP pancreatitis, bleeding and perforation as primary outcomes. RESULTS: Three RCTs including a total of 594 patients met the inclusion criteria. Our meta-analysis results showed the rate of post-ERCP pancreatitis, primarily mild to moderate pancreatitis, was no different between Endocut versus blended current modes [risk ratio (RR) 0.61, 95% confidence interval (CI) 0.25-1.52, P = 0.29]. However, the risk of endoscopically bleeding events, primarily mild bleeding, was lower in studies using Endocut versus blended current (RR 0.54, 95% CI 0.31-0.95, P = 0.03). Notably, none of the patients experienced perforation in these three trials. CONCLUSIONS: The rate of post-ERCP pancreatitis was not significantly different when using the Endocut versus blended current during EST. Nevertheless, compared with the blended current, Endocut reduced the incidence of endoscopically evident bleeding; however, the available data were insufficient to assess the perforation risk.

Suppressing microRNA-29c promotes biliary atresia-related fibrosis by targeting DNMT3A and DNMT3B.

This study was designed to investigate the potential role of microRNA-29c (miR-29c) in biliary atresia-related fibrosis. The expression of miR-29c was determined in 15 pairs of peripheral blood samples from infants with biliary atresia (BA) and infants with non-BA neonatal cholestasis using quantitative real-time PCR. EMT was established by induction with TGF-ß1 in HIBEpiC cells. MiR-29c was inhibited by lipofectamine transfection. The expressions of proteins related to epithelial-mesenchymal transition (EMT), i.e., E-cadherin, N-cadherin and vimentin, were determined using quantitative real-time PCR and western blotting. Direct interaction between miR-29c and DNMT3A and DNMT3B was identified using a luciferase reporter assay. The expressions of DNMT3A and DNMT3B were suppressed by treatment with SGI-1027. Patients with BA showed significantly lower miR-29c levels in peripheral blood samples than the control subjects. In vitro, TGF-ß1-induced EMT significantly decreased the expression of miR-29c. Downregulation of miR-29c had a promotional effect on BA-related fibrosis in HIBEpiC cells, as confirmed by the decrease in E-cadherin and increase in N-cadherin and vimentin levels. MiR-29c was found to target the 3'UTR of DNMT3A and DNMT3B and inhibit their expression. Suppression of DNMT3A and DNMT3B reversed the effects of miR-29c downregulation on BA-related fibrosis in HIBEpiC cells. These data suggest that BA-related fibrosis is closely associated with the occurrence of EMT in HIBEpiC cells. MiR-29c might be a candidate for alleviating BA-related fibrosis by targeting DNMT3A and DNMT3B.

Design and Synthesis of Novel Thiazolo[5,4-d]pyrimidine Derivatives as Potential Angiogenesis Inhibitors.

Vascular endothelial growth factor receptor-2 (VEGFR-2) plays an important role in both vasculogenesis and angiogenesis. Inhibition of VEGFR-2 has been demonstrated as a key method against tumor-associated angiogenesis. Thiazolopyrimidine is an important analog of the purine ring, and we choose the thiazolopyrimidine scaffold as the mother nucleus. Two series of thiazolo[5,4-d]pyrimidine derivatives were synthesized and evaluated for their antiproliferative activity. In HUVEC inhibition assay, compounds 3l (=1-(5-{[2-(4-chlorophenyl)-5-methyl[1,3]thiazolo[5,4-d]pyrimidin-7-yl]amino}pyridin-2-yl)-3-(3,4-dimethylphenyl)urea) and 3m (=1-(5-{[2-(4-chlorophenyl)-5-methyl[1,3]thiazolo[5,4-d]pyrimidin-7-yl]amino}pyridin-2-yl)-3-(4-methoxyphenyl)urea) exhibited the most potent inhibitory effect (IC50 =1.65 and 3.52 µm, respectively). Compound 3l also showed the best potency against VEGFR-2 at 50 µm (98.5 %). These results suggest that further investigation of compound 3l might provide potential angiogenesis inhibitors.

Effective heat dissipation in an adiabatic near-field transducer for HAMR.

To achieve a feasible heat-assisted magnetic recording (HAMR) system, a near-field transducer (NFT) is necessary to strongly focus the optical field to a lateral region measuring tens of nanometres in size. An NFT must deliver sufficient power to the recording medium as well as maintain its structural integrity. The self-heating problem in the NFT causes materials failure that leads to the degradation of the hard disk drive performance. The literature reports NFT structures with physical sizes well below 1 micron which were found to be thermo-mechanically unstable at an elevated temperature. In this paper, we demonstrate an adiabatic NFT to address the central challenge of thermal engineering for a HAMR system. The NFT is formed by an isosceles triangular gold taper plasmonic waveguide with a length of 6 µm and a height of 50 nm. Our study shows that in the full optically and thermally optimized system, the NFT efficiently extracts the incident light from the waveguide core and can improve the shape of the heating source profile for data recording. The most important insight of the thermal performance is that the recording medium can be heated up to 866 K with an input power of 8.5 mW which is above the Curie temperature of the FePt film while maintaining the temperature in the NFT at 390 K without a heat spreader. A very good thermal efficiency of 5.91 is achieved also. The proposed structure is easily fabricated and can potentially reduce the NFT deformation at a high recording temperature making it suitable for practical HAMR application.

Value of flaccid penile ultrasound in screening for arteriogenic impotence: a preliminary prospective study.

BACKGROUND: This prospective study is to evaluate the potential value of sonographic measurements in the flaccid penis for the screening of arteriogenic impotence. METHODS: A consecutive series of 260 Chinese males consulting for sexual dysfunction and 54 controls underwent sonographic examination. The sonographic parameters were correlated with the clinical gold standards, including the international index of erectile function (IIEF) and penile erectile hardness grading scale (EHGS). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the receiver operating characteristic curve (AUROC) of flaccid peak systolic velocity (PSV) in predicting patients with normal function were analyzed. RESULTS: The mean cavernous PSV of both sides in the patients with sexual dysfunction ranged from 7.76 to 11.12 cm/sec with a stepwise increase in IIEF and EHGS grading scale (P < .05). The cutoff value of flaccid PSV for the differential diagnosis of grade 4 of IIEF-5 or EHGS was 8.20-8.90 cm/sec, with an AUROC of 0.657-0.724, specificity of 82.96-86.84% and PPV of 95.20-96.60%, respectively. CONCLUSIONS: This simple flaccid PSV measurement is a specific tool for screening arteriogenic impotence.

Vertical Single-Crystalline Organic Nanowires on Graphene: Solution-Phase Epitaxy and Optical Microcavities.

Vertically aligned nanowires (NWs) of single crystal semiconductors have attracted a great deal of interest in the past few years. They have strong potential to be used in device structures with high density and with intriguing optoelectronic properties. However, fabricating such nanowire structures using organic semiconducting materials remains technically challenging. Here we report a simple procedure for the synthesis of crystalline 9,10-bis(phenylethynyl) anthracene (BPEA) NWs on a graphene surface utilizing a solution-phase van der Waals (vdW) epitaxial strategy. The wires are found to grow preferentially in a vertical direction on the surface of graphene. Structural characterization and first-principles ab initio simulations were performed to investigate the epitaxial growth and the molecular orientation of the BPEA molecules on graphene was studied, revealing the role of interactions at the graphene-BPEA interface in determining the molecular orientation. These free-standing NWs showed not only efficient optical waveguiding with low loss along the NW but also confinement of light between the two end facets of the NW forming a microcavity Fabry-Pérot resonator. From an analysis of the optical dispersion within such NW microcavities, we observed strong slowing of the waveguided light with a group velocity reduced to one-tenth the speed of light. Applications of the vertical single-crystalline organic NWs grown on graphene will benefit from a combination of the unique electronic properties and flexibility of graphene and the tunable optical and electronic properties of organic NWs. Therefore, these vertical organic NW arrays on graphene offer the potential for realizing future on-chip light sources.

Tracking the Evolution of Polymer Interface Films during the Process of Thermal Annealing at the Domain and Single Molecular Levels using Scanning Tunneling Microscopy.

Structural evolution of polymer (NTZ12) interface films during the process of annealing is revealed at the domain and single molecular levels using the statistical data measured from scanning tunneling microscopy images and through theoretical calculations. First, common features of the interface films are examined. Then, mean values of surface-occupied ratio, size and density of the domain are used to reveal the intrinsic derivation of the respective stages. Formation of new domains is triggered at 70 °C, but domain ripening is not activated. At 110 °C, the speed of formation of new domains is almost balanced by the consumption due to the ripening process. However, formation of new domains is reduced heavily at 150 °C but restarted at 190 °C. At the single molecular level, the ratio of the average length of linear to curved backbones is increased during annealing, whereas the ratios of the total length and the total number of linear to curved skeletons reaches a peak value at 150 °C. The two major conformations of curved backbones for all samples are 120° and 180° bending, but the ripening at 150 °C reduces 180° folding dramatically. Molecular dynamic simulations disclose the fast relaxing process of curved skeletons at high temperature.

Summary of biological research on hepatoblastoma: a scoping review.

Background: Hepatoblastoma is the most prevalent primary hepatic malignancy in children, comprising 80% of pediatric hepatic malignancies and 1% of all pediatric malignancies. However, traditional treatments have proven inadequate in effectively curing hepatoblastoma, leading to a poor prognosis. Methods: A literature search was conducted on multiple electronic databases (PubMed and Google Scholar). A total of 86 articles were eligible for inclusion in this review. Result: This review aims to consolidate recent developments in hepatoblastoma research, focusing on the latest advances in cancer-associated genomics, epigenetic studies, transcriptional programs and molecular subtypes. We also discuss the current treatment approaches and forthcoming strategies to address cancer-associated biological challenges. Conclusion: To provide a comprehensive summary of the molecular mechanisms associated with hepatoblastoma occurrence, this review highlights three key aspects: genomics, epigenetics, and transcriptomics. Our review aims to facilitate the exploration of novel molecular mechanisms and the development of innovative clinical treatment strategies for hepatoblastoma.

Injectable Hydrogels Prepared Using Novel Synthetic Short Peptides with Defined Structure and Gelatin as Scaffolds to Support Cell and Tissue Growth.

Animal-derived basement-membrane matrices such as Geltrex are used to grow cells and tissues. Particularly, these are commonly applied to support tumor growth in animals for cancer research. However, a material derived from an animal source has an undefined composition, and may thus have unavoidable batch-to-batch variation in properties. To overcome these issues, a series of synthetic short peptides to form hydrogels is designed in combination with gelatin to promote cell adhesion and growth. The peptides have sequences of (X1Y1X2Y2)2 , where X1 and X2 are hydrophobic residues, while Y1 and Y2 are hydrophilic residues. The peptides spontaneously fold and self-assemble into a ß-sheet secondary structure upon contact with salts, and then aggregate to form hydrophilic networks of hydrogels. Hybrid hydrogels formed by mixing the peptide IEVEIRVK (IVK8) with gelatin are injectable and enzymatically degradable. The hybrid hydrogels at optimal compositions support SW480 and HepG2 tumor spheroid growth in vitro as effectively as Geltrex. More importantly, the peptide/gelatin hydrogels support tumor growth in a SW480 human colorectal adenocarcinoma xenograft mouse model. Altogether, the results illustrate that the synthetic peptide/gelatin hybrid hydrogel is a promising scaffold that can be used to support cell and tissue growth both in vitro and in vivo.

["Load-Unload" Effect of Manganese Oxides on Phosphorus in Surface Water of the Pearl River Estuary].

Phosphorus (P) conveyed by surface runoff plays an essential role in regulating nutrient balance and primary production in estuarine waters. In this study, basic physiochemical properties, total phosphorus (TP, including speciation), particulate iron (PFe), particulate manganese (PMn), and particulate aluminum (PAl) of the surface water in the Pearl River Estuary (PRE) in different seasons were determined to investigate the spatiotemporal distribution characteristics of P and to identify the crucial factor controlling P migration and transformation in the freshwater-saltwater interaction zone. TP concentrations (28.88-233.68 µg·L-1) decreased with increasing salinity gradient owing to deposition and dilution. The proportions of P speciation followed a decreasing order as dissolved inorganic phosphorus (DIP, 37.3%) > particulate inorganic phosphorus (PIP, 22.7%) > dissolved organic phosphorus (DOP, 21.0%) > particulate organic phosphorus (POP, 19.0%). PIP was positively related to PFe, PMn, and PAl (P < 0.05), confirming their concurrent migration behaviors. In addition, the increase in salinity promoted the desorption of phosphate on the suspended particulate matters, which mainly took place near the freshwater-saltwater interface. A significant positive correlation (P < 0.001) between the solid-liquid phase partitioning coefficient (Kd) of phosphate and salinity indicated that PIP was present mainly in more stable forms in the brackish water. Most importantly, a better relationship between Kd and PMn (P < 0.01) supported our scientific hypothesis of the "load-unload" effect of Mn oxides on P:particulate-carrying phosphates transported from the freshwater zone tend to be desorbed and released into the brackish water.

Osteoarticular tuberculosis cases in the southwest of China: A 9-year retrospective study.

Background: Osteoarticular tuberculosis (TB) is an uncommon form of extrapulmonary TB. In this study, we analyzed the epidemiological characteristics, common sites, and drug resistance profiles of osteoarticular TB infections occurring in southwest China. Methods: A total of 3,254 cases of patients clinically diagnosed with osteoarticular TB infections between 2013 and 2021 were retrospectively analyzed. Patients' demographic and clinical characteristics were collected. Drug sensitivity testing was performed using the microporous plate ratio method. Chi-squared analysis was used to analyze the rates of and trends in mycobacterial isolates. Results: Of the 3,254 patients, 1,968 (60.5%) were men and boys, and 1,286 (39.5%) were women and girls; patients' ages ranged from 1 to 91 years, with an average of 42 ± 19.3 years. In terms of disease, 2,261 (69.5%) had spinal TB, mainly thoracic (815, 36%) or lumbar (1,080, 48%); joint TB was found in 874 cases (26.9%), mainly occurring in the knee (263, 30%) or hip (227, 26%); and both spinal and joint TB were observed in 119 cases (3.7%). Drug susceptibility tests were performed on 241 isolated strains of MTB; 70 strains (29.0%) were resistant to at least one drug, and MDR-TB and XDR-TB were observed in 7.1 and 1.2% of strains, respectively. Conclusions: In southwest China over this period, osteoarticular TB mainly affected middle-aged and young men with poor nutritional status. Patients from ethnic minority areas also accounted for a large proportion of cases. Spinal TB is prone to occur in the lumbar and thoracic vertebrae, and joint TB is prone to occur in the lower limb joints. Additionally, there has been an increasing trend in the number of TB cases over the past 9 years, and drug resistance has also increased.

Ru(II) Complexes with Enaminone Structures for Rapid Sterilization of Staphylococcus aureus and MRSA with Little Accumulation of Drug Resistance.

Drug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), pose a serious threat to human life. Therefore, there is urgent need to develop antibiotics with new chemical structures and antibacterial mechanisms, especially those that elicit little drug resistance after long-term use. Herein we synthesized three novel ruthenium complexes (Ru1-Ru3) containing the enaminone structures for the first time. At a concentration of 5 µM, Ru1-Ru3 can lead to a CFU reduction of about 5 log units towards S. aureus and MRSA. Interestingly, Ru3 displayed rapid bactericidal effects and could decrease the CFU numbers of both pathogens by 5 log units within 40 min. The control compounds (Ru4 and Ru5) without the enaminone structures displayed very poor antibacterial activity under the same conditions. Moreover, S. aureus did not show apparent drug resistance towards Ru3 after 20 passages incubation with a sublethal concentration. These results highlight the critical role of enaminone structures for antibacterial applications.