Emergence of large-scale cell death through ferroptotic trigger waves.

Large-scale cell death is commonly observed during organismal development and in human pathologies1-5. These cell death events extend over great distances to eliminate large populations of cells, raising the question of how cell death can be coordinated in space and time. One mechanism that enables long-range signal transmission is trigger waves6, but how this mechanism might be used for death events in cell populations remains unclear. Here we demonstrate that ferroptosis, an iron- and lipid-peroxidation-dependent form of cell death, can propagate across human cells over long distances (≥5 mm) at constant speeds (around 5.5 µm min-1) through trigger waves of reactive oxygen species (ROS). Chemical and genetic perturbations indicate a primary role of ROS feedback loops (Fenton reaction, NADPH oxidase signalling and glutathione synthesis) in controlling the progression of ferroptotic trigger waves. We show that introducing ferroptotic stress through suppression of cystine uptake activates these ROS feedback loops, converting cellular redox systems from being monostable to being bistable and thereby priming cell populations to become bistable media over which ROS propagate. Furthermore, we demonstrate that ferroptosis and its propagation accompany the massive, yet spatially restricted, cell death events during muscle remodelling of the embryonic avian limb, substantiating its use as a tissue-sculpting strategy during embryogenesis. Our findings highlight the role of ferroptosis in coordinating global cell death events, providing a paradigm for investigating large-scale cell death in embryonic development and human pathologies.

Structure-aware dual-target drug design through collaborative learning of pharmacophore combination and molecular simulation.

Dual-target drug design has gained significant attention in the treatment of complex diseases, such as cancers and autoimmune disorders. A widely employed design strategy is combining pharmacophores to leverage the knowledge of structure-activity relationships of both targets. Unfortunately, pharmacophore combination often struggles with long and expensive trial and error, because the protein pockets of the two targets impose complex structural constraints. In this study, we propose AIxFuse, a structure-aware dual-target drug design method that learns pharmacophore fusion patterns to satisfy the dual-target structural constraints simulated by molecular docking. AIxFuse employs two self-play reinforcement learning (RL) agents to learn pharmacophore selection and fusion by comprehensive feedback including dual-target molecular docking scores. Collaboratively, the molecular docking scores are learned by active learning (AL). Through collaborative RL and AL, AIxFuse learns to generate molecules with multiple desired properties. AIxFuse is shown to outperform state-of-the-art methods in generating dual-target drugs against glycogen synthase kinase-3 beta (GSK3ß) and c-Jun N-terminal kinase 3 (JNK3). When applied to another task against retinoic acid receptor-related orphan receptor γ-t (RORγt) and dihydroorotate dehydrogenase (DHODH), AIxFuse exhibits consistent performance while compared methods suffer from performance drops, leading to a 5 times higher performance in success rate. Docking studies demonstrate that AIxFuse can generate molecules concurrently satisfying the binding mode required by both targets. Further free energy perturbation calculation indicates that the generated candidates have promising binding free energies against both targets.

Development of an angle-adjustable photonic crystal fluorescence platform for sensitive detection of oxytetracycline.

We pioneered an angle-adjustable photonic crystal fluorescence platform (APC-Fluor) that integrates PCs, an angular resolution spectrometer and a strategically aligned laser source. This configuration, featuring a coaxial rotating swing arm, allows for precise control over the angles of incidence and emission. The presence of photonic crystal microcavities facilitates the dispersion of fluorescent materials and promotes the transition of electrons from the excited state to the lowest vibrational energy level. The optical resonance effect triggered by modulating the alignment of the reflection peaks of the photonic crystals with the emission peaks of the fluorescent materials can significantly enhance the fluorescence intensity. Compared with the single BSA-AuNCs, the optimized fluorescence intensity can be significantly increased by 11.9-fold. The APC-Fluor system showcases rapid and highly sensitive detection capabilities for oxytetracycline (OTC), exhibiting a response across a concentration range from 2 to 1 × 104 nM and achieving a notably low detection limit of 1.03 nM.

Analysis of bacterial transcriptome and epitranscriptome using nanopore direct RNA sequencing.

Bacterial gene expression is a complex process involving extensive regulatory mechanisms. Along with growing interests in this field, Nanopore Direct RNA Sequencing (DRS) provides a promising platform for rapid and comprehensive characterization of bacterial RNA biology. However, the DRS of bacterial RNA is currently deficient in the yield of mRNA-mapping reads and has yet to be exploited for transcriptome-wide RNA modification mapping. Here, we showed that pre-processing of bacterial total RNA (size selection followed by ribosomal RNA depletion and polyadenylation) guaranteed high throughputs of sequencing data and considerably increased the amount of mRNA reads. This way, complex transcriptome architectures were reconstructed for Escherichia coli and Staphylococcus aureus and extended the boundaries of 225 known E. coli operons and 89 defined S. aureus operons. Utilizing unmodified in vitro-transcribed (IVT) RNA libraries as a negative control, several Nanopore-based computational tools globally detected putative modification sites in the E. coli and S. aureus transcriptomes. Combined with Next-Generation Sequencing-based N6-methyladenosine (m6A) detection methods, 75 high-confidence m6A candidates were identified in the E. coli protein-coding transcripts, while none were detected in S. aureus. Altogether, we demonstrated the potential of Nanopore DRS in systematic and convenient transcriptome and epitranscriptome analysis.

All-Cellulose Nanofiber-Based Sustainable Triboelectric Nanogenerators for Enhanced Energy Harvesting.

Triboelectric nanogenerators (TENGs) show promising potential in energy harvesting and sensing for various electronic devices in multiple fields. However, the majority of materials currently utilized in TENGs are unrenewable, undegradable, and necessitate complex preparation processes, resulting in restricted performance and durability for practical applications. Here, we propose a strategy that combines straightforward chemical modification and electrospinning techniques to construct all-cellulose nanofiber-based TENGs with substantial power output. By using cellulose acetate (CA) as the raw material, the prepared cellulose membranes (CMs) and fluorinated cellulose membranes (FCMs) with different functional groups and hydrophobic properties are applied as the tribopositive and tribonegative friction layers of FCM/CM-based triboelectric nanogenerators (FC-TENGs), respectively. This approach modulates the microstructure and triboelectric polarity of the friction materials in FC-TENGs, thus enhancing their triboelectric charge densities and contact areas. As a result, the assembled FC-TENGs demonstrate enhanced output performance (94 V, 8.5 µA, and 0.15 W/m2) and exceptional durability in 15,000 cycles. The prepared FC-TENGs with efficient energy harvesting capabilities can be implemented in practical applications to power various electronic devices. Our work strengthens the viability of cellulose-based TENGs for sustainable development and provides novel perspectives on the cost-effective and valuable utilization of cellulose in the future.

Cystatin SN (CST1) Is a Poor Independent Prognostic Biomarker for Gastrointestinal Diffuse Large B-Cell Lymphoma.

BACKGROUND Gastrointestinal diffuse large B-cell lymphoma (GI-DLBCL) is the most common histological subtype of extra-nodal DLBCL, but the risk factors, prognostic biomarkers, histopathological classifications, and treatment strategies have not had significant progress. Emerging evidence shows that cystatin SN (CST1) is involved in tumor progression in several cancer types, but its role in GI-DLBCL has not been revealed. MATERIAL AND METHODS We established a cohort consisting of 84 patients with GI-DLBCL who underwent surgical resection. The expression of CST1 in the cohort was investigated by immunohistochemistry, which divided the patients into subgroups with low or high expression of CST1. Moreover, the CST1 expression in GI-DLBCL tissues or adjacent GI tissues were compared with RT-qPCR. The correlation between CST1 expression and clinicopathological factors was analyzed with the chi-square test. The prognostic significance of CST1 was estimated by univariate and multivariate analysis, and statistical significance was analyzed with the log-rank test. RESULTS CST1 was aberrantly upregulated in GI-DLBCL tissues compared with in non-tumor GI tissues. High expression of CST1 indicated poor prognosis of GI-DLBCL (P=0.012), and CST1 can be regarded as an independent prognostic biomarker of GI-DLBCL (hazard ratio=3.07). In our study, serum lactate dehydrogenase (P=0.002), performance status (P=0.003), Lugano stage (P=0.002), and International Prognostic Index (P=0.001) were also prognostic factors of GI-DLBCL. CONCLUSIONS CST1 is an independent prognostic biomarker of GI-DLBCL, indicating unfavorable prognosis. Our results suggested that CST1 detection can be a promising method to stratify high-risk patients and guide individual treatment.

Development of an effective meropenem/KPC-2 inhibitor combination to combat infections caused by carbapenem-resistant K. pneumoniae.

The global public health threat of bacterial antibiotic resistance continues to escalate and necessitates the implementation of urgent measures to expand our arsenal of antimicrobial drugs. In this study, we identified a benzoxaborane compound, namely 5-chloro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole (AN2178), which can effectively inhibit the catalytic activity of the Klebsiella pneumoniae carbapenemase (KPC-2) enzyme. The efficacy of AN2718 as an inhibitor for the KPC-2 enzyme was verified through various assays, including enzyme activity assays and isothermal titration calorimetry. Results of multiple biochemical assays, minimum inhibitory concentration assay, and time-killing assay also showed that binding of AN2718 to KPC-2 enabled the restoration of the bactericidal effect of meropenem. The survival rate of mice infected by carbapenem-resistant, high-virulence strains increased significantly upon treatment with this agent. Most importantly, the meropenem and AN2718 combination is effective on KPC-2 mutations such as KPC-33 that were clinically evolved and exhibited resistance to ceftazidime-avibactam upon the clinical uses of this drug for a couple of years. Comprehensive safety tests both in vitro and in vivo, such as cytotoxicity, haemolytic activity, and cytochrome P450 inhibition assays demonstrated that AN2718 was safe for clinical use. These promising data indicate that AN2718 has a high potential for being approved for the treatment of drug resistant bacterial infections, including those caused by the Ceftazidime-Avibactam resistant strains. To conclude, the compound AN2718 can be regarded as a valuable addition to the current antimicrobial armamentarium and a promising tool to combat antimicrobial resistance.

Ultrasound-guided percutaneous radiofrequency ablation versus surgery for solitary T1N0M0 papillary thyroid carcinoma in the danger triangle.

OBJECTIVES: To compare the safety and efficiency of ultrasound-guided percutaneous radiofrequency ablation (RFA) and surgical resection (SR) for thyroid papillary carcinoma (PTC) in the danger triangle area. METHODS: The clinical data of 298 patients who underwent either percutaneous RFA or SR for PTC in the thyroid danger triangle at our hospital between January 2018 and April 2020 were retrospectively analyzed. Propensity score matching is employed to regulate for confounding factors. All patients undergoing ablation were treated using a strategy that combined sufficient paratracheal fluid isolation with a low-power, short electrode. Disease progression was analyzed in patients with T1N0M0 PTC (T1a and T1b) employed in Kaplan‒Meier curves. Treatment parameters and the rates of local recurrence, distant metastasis, and complications are recorded and compared. RESULTS: Of 182 eligible patients who were included, 91 were in the RFA (age 44.84 ± 13.19; 71 females; 77 T1a) and 91 were in the SR (age 47.36 ± 11.05; 68 females; 69 T1a). The average treatment time, length of hospital stays, blood loss volume, and scar length are substantially less in the RFA than in the SR. Major complications as well as postoperative permanent recurrent laryngeal nerve injury and postoperative transient parathyroid dysfunction occurred only in the SR, with a substantial distinction between the two groups (p < 0.05). There is no substantial distinction in the disease progression between RFA and SR treatment of T1N0M0 PTC. CONCLUSION: RFA is as effective as surgery for PTC in the danger triangle area in the short term, with faster recovery and fewer complications. CLINICAL RELEVANCE STATEMENT: Radiofrequency ablation has a clinical efficacy comparable to surgery in the treatment of papillary thyroid carcinoma in the danger triangle area in the short term with the advantages of faster recovery and fewer complications when compared with surgery. KEY POINTS: Use of radiofrequency ablation (RFA) in the thyroid danger triangle is still controversial. RFA and surgery groups showed no difference in disease progressions, and no major complications occurred with RFA. Radiofrequency ablation offers a new option for papillary thyroid carcinoma patients in the danger triangle.

Simulation and experimental study of gas-phase diffusion coefficient of selenium dioxide.

Improving the removal effect of selenium in wet flue gas desulfurization system is a key way to reduce the emission of selenium pollutants from coal-fired power plants. In order to clarify the removal mechanism of selenium pollutants in the desulfurization tower, it is necessary to obtain accurate selenium gas-phase diffusion coefficient. In this paper, molecular dynamics simulations were used to carry out theoretical calculations of gas-phase diffusion coefficients of SeO2 (the main form of selenium in coal combustion flue gas). The gas-phase diffusion coefficients of SeO2 in the range of 393 K-433 K were measured by a self-developed heavy metal gas diffusion coefficient testing device to verify the accuracy of the molecular dynamics calculations. Furthermore, the calculated gas-phase diffusion coefficients of SeO2 under typical binary and ternary components were obtained by correcting on the basis of Fuller's formula. Finally, a single-droplet absorption model for SeO2 was constructed and experiments were carried out to compare the effect of the gas-phase diffusion coefficient on the accuracy of the model calculations. The error of the model calculations was reduced from 8.09 % to 1.96 % after the correction. In this study, the gas-phase diffusion coefficient of SeO2 in the low-temperature range of coal-fired flue gas was obtained. This study can provide basic data for the development of selenium migration mechanism and control technology.

GV-971 attenuates the progression of neuromyelitis optica in murine models and reverses alterations in gut microbiota and associated peripheral abnormalities.

AIMS: Growing evidence suggests that an imbalanced gut microbiota composition plays a crucial role in the development of neuromyelitis optica spectrum disorders (NMOSD), an inflammatory demyelinating disease primarily affecting the optic nerves and central nervous system (CNS). In light of this, we explored the potential therapeutic benefits of GV-971 in NMOSD. GV-971 is a drug used for treating mild-to-moderate Alzheimer's disease, which targets the gut-brain axis and reduces neuroinflammation. METHODS: To evaluate GV-971's effects, we employed the experimental autoimmune encephalomyelitis (EAE) mouse model to establish NMOSD animal models. This was achieved by injecting NMO-IgG into aged mice (11 months old) or using NMO-IgG along with complement injection and microbubble-enhanced low-frequency ultrasound (MELFUS) techniques in young mice (7 weeks old). We assessed the impact of GV-971 on incidence rate, clinical scores, body weight, and survival, with methylprednisolone serving as a positive control. In NMOSD models of young mice, we analyzed spinal cord samples through H&E staining, immunohistochemistry, and Luxol Fast Blue staining. Fecal samples collected at different time points underwent 16S rRNA gene sequencing, while plasma samples were analyzed using cytokine array and untargeted metabolomics analysis. RESULTS: Our findings indicated that GV-971 significantly reduced the incidence of NMOSD, alleviated symptoms, and prolonged survival in NMOSD mouse models. The NMOSD model exhibited substantial neuroinflammation and injury, accompanied by imbalances in gut microbiota, peripheral inflammation, and metabolic disorders, suggesting a potentially vicious cycle that accelerates disease pathogenesis. Notably, GV-971 effectively reduces neuroinflammation and injury, and restores gut microbiota composition, as well as ameliorates peripheral inflammation and metabolic disorders. CONCLUSIONS: GV-971 attenuates the progression of NMOSD in murine models and reduces neuroinflammation and injury, likely through its effects on remodeling gut microbiota and peripheral inflammation and metabolic disorders.

A new synonym of Rhododendronleishanicum (subg. Hymenanthes) from China (Ericaceae).

Based on a critical examination of type specimens, images of living plants, and the literature has shown Rhododendronoligocarpum to be conspecific with R.leishanicum. Although slight variations in corolla colour exist amongst different populations of R.oligocarpum, it does not serve as a key distinguishing trait. Therefore, we reduced R.oligocarpum to a synonym of R.leishanicum, and recommend placing it in Subsection Maculifera.

Identifying MiR-140-3p as a stable internal reference to normalize MicroRNA qRT-PCR levels of plasma small extracellular vesicles in lung cancer patients.

Exploration of a stably expressed gene as a reference is critical for the accurate evaluation of miRNAs isolated from small extracellular vesicles (sEVs). In this study, we analyzed small RNA sequencing on plasma sEV miRNAs in the training dataset (n = 104) and found that miR-140-3p was the most stably expressed candidate reference for sEV miRNAs. We further demonstrated that miR-140-3p expressed most stably in the validation cohort (n = 46) when compared to two other reference miRNAs, miR-451a and miR-1228-3p, and the commonly-used miRNA reference U6. Finally, we compared the capability of miR-140-3p and U6 as the internal reference for sEV miRNA expression by evaluating key miRNAs expression in lung cancer patients and found that miR-140-3p was more suitable as a sEV miRNA reference gene. Taken together, our data indicated miR-140-3p as a stable internal reference miRNA of plasma sEVs to evaluate miRNA expression profiles in lung cancer patients.

A Selective FGFR1/2 PROTAC Degrader with Antitumor Activity.

The aberrant activation of FGFR acts as a potent driver of multiple types of human cancers. Despite the development of several conventional small-molecular FGFR inhibitors, their clinical efficacy is largely compromised because of low selectivity and side effects. In this study, we report the selective FGFR1/2-targeting proteolysis-targeting chimera BR-cpd7 that displays significant isoform specificity to FGFR1/2 with half maximal degradation concentration values around 10 nmol/L while sparing FGFR3. The following mechanistic investigation reveals the reduced FGFR signaling, through which BR-cpd7 induces cell-cycle arrest and consequently blocks the proliferation of multiple FGFR1/2-dependent tumor cells. Importantly, BR-cpd7 has almost no antiproliferative activity against cancer cells without FGFR aberrations, furtherly supporting its selectivity. In vivo, BR-cpd7 exhibits robust antitumor effects in FGFR1-dependent lung cancer at well-tolerated dose schedules, accompanied by complete FGFR1 depletion. Overall, we identify BR-cpd7 as a promising candidate for developing a selective FGFR1/2-targeted agent, thereby offering a new therapeutic strategy for human cancers in which FGFR1/2 plays a critical role.

Comparison of the predictive performance of three lymph node staging systems for late-onset gastric cancer patients after surgery.

Introduction: Lymph node (LN) status is a vital prognostic factor for patients. However, there has been limited focus on predicting the prognosis of patients with late-onset gastric cancer (LOGC). This study aimed to investigate the predictive potential of the log odds of positive lymph nodes (LODDS), lymph node ratio (LNR), and pN stage in assessing the prognosis of patients diagnosed with LOGC. Methods: The LOGC data were obtained from the Surveillance, Epidemiology, and End Results database. This study evaluated and compared the predictive performance of three LN staging systems. Univariate and multivariate Cox regression analyses were carried out to identify prognostic factors for overall survival (OS). Three machine learning methods, namely, LASSO, XGBoost, and RF analyses, were subsequently used to identify the optimal LN staging system. A nomogram was built to predict the prognosis of patients with LOGC. The efficacy of the model was demonstrated through receiver operating characteristic (ROC) curve analysis and decision curve analysis. Results: A total of 4,743 patients with >16 removed lymph nodes were ultimately included in this investigation. Three LN staging systems demonstrated significant performance in predicting survival outcomes (P < 0.001). The LNR exhibited the most important prognostic ability, as evidenced by the use of three machine learning methods. Utilizing independent factors derived from multivariate Cox regression analysis, a nomogram for OS was constructed. Discussion: The calibration, C-index, and AUC revealed their excellent predictive performance. The LNR demonstrated a more powerful performance than other LN staging methods in LOGC patients after surgery. Our novel nomogram exhibited superior clinical feasibility and may assist in patient clinical decision-making.

Potential COVID-19 remedies from repurposed drugs and herbal small RNAs.

To date, SARS-CoV-2 has caused millions of deaths, but the choice of treatment is limited. We previously established a platform for identifying Food and Drug Administration (FDA)-approved repurposed drugs for avian influenza A virus infections that could be used for coronavirus disease 2019 (COVID-19) treatment. In this study, we analyzed blood samples from two cohorts of 63 COVID-19 patients, including 19 patients with severe disease. Among the 39 FDA-approved drugs we identified for COVID-19 therapy in both cohorts, 23 drugs were confirmed by literature mining data, including 14 drugs already under COVID-19 clinical trials and 9 drugs reported for COVID-19 treatments, suggesting the remaining 16 FDA-approved drugs may be candidates for COVID-19 therapy. Additionally, we previously reported that herbal small RNAs (sRNAs) could be effective components in traditional Chinese medicine (TCM) for treating COVID-19. Based on the abundance of sRNAs, we screened the 245 TCMs in the Bencao (herbal) sRNA Atlas that we had previously established, and we found that the top 12 TCMs for COVID-19 treatment was consistent across both cohorts. We validated the efficiency of the top 30 sRNAs from each of the top 3 TCMs for COVID-19 treatment in poly(I:C)-stimulated human non-small cell lung cancer cells (A549 cells). In conclusion, our study recommends potential COVID-19 remedies using FDA-approved repurposed drugs and herbal sRNAs from TCMs.

Total Syntheses of Streptamidine and Klebsazolicin Using Biomimetic On-Resin Ring-Closing Amidine Formation.

Diketopiperazine (DKP) derived cyclic amidine structures widely exist in peptide natural products according to the genome mining result. The largely unknown bioactivity and mode of action are partially caused by the poor availability of the compounds via microbiological and chemical approaches. To tackle this challenge, in this work, we have developed the on-resin ring-closing amidine formation strategy to synthesize peptides containing N-terminal DKP derived cyclic amidine structure, in which the 6-exo-trig cyclization mediated by HgCl2 activation of thioamides was the key step. Leveraging from this new strategy, we finished the total syntheses of streptamidine and klebsazolicin. Meanwhile, eleven klebsazolicin analogues were synthesized for its structure-activity relationship study.

Emergence of a novel GIII Getah virus variant in pigs in Guangdong, China, 2023.

From May to July of 2023, one pig farm in Heyuan city, Guangdong Province of China, suffered severe piglet death and sow reproductive disorders. The common pig viruses and bacteria tested negative. To uncover the possible cause of the disease, a metagenomic analysis was performed in the pooled small intestine samples from three 8-day-old diseased piglets. The results showed that Getah virus (GETV), an RNA virus, might be the potential pathogen that affects pig health. Subsequently, GETV nucleotide was detected in all of the 15 samples collected from three diseased piglets using quantitative reverse transcription PCR, suggesting GETV as the main pathogen of the disease. A GETV strain, designated as GDHYLC23, was successfully isolated using the swine testicle cell line. Sequence analysis showed that the epidemic strain had a unique 32-nucleotide repeat insertion in the 3' noncoding region. Phylogenetic analysis showed that GDHYLC23 belonged to the pandemic group III. The identification of GETV with new variations implies the continuous evolution of the virus, which poses potential threats to the swine industry.IMPORTANCEPig farms are faced with emerging and re-emerging viruses that may cause substantial economic loss. The identification of potentially pathogenic viruses helps to prevent and control the spread of diseases. In this study, by using metagenomic analysis, we found that a neglected virus, GETV with a unique insertion in the genome, was the main pathogen in one pig farm that suffered severe piglet death and sow reproductive disorders. Although the potential impact of such an insertion on viral pathogenicity is unknown, the surveillance of the continuing evolution of GETV in pig farms cannot be ignored.

Exosomal circ_CCDC7/gga-miR-6568-3p/Pax7 axis accelerates the differentiation of chicken embryonic stem cells infected with subgroup J avian leukosis virus.

Exosome-mediated horizontal and vertical transmission of subgroup J avian leukosis virus (ALV-J) in poultry flocks can lead to growth inhibition and severe immunosuppression. However, there are few reports on the early infection of chicken embryonic stem cells (cESCs) with ALV-J. In this study, we confirmed that early infection with ALV-J can accelerate the differentiation of cESCs and promote the secretion of exosomes. To investigate the modulation strategy of ALV-J in cESCs, circRNA sequencing was performed for further analysis. A total of 305 differentially expressed circRNAs (DECs) were obtained, including 71 upregulated DECs. Circ-CCDC7 was found to be the most upregulated DEC and was assessed by qRT-PCR, with the result consistent with the result of circRNA-seq. Based on qRT-PCR, gga-miR-6568-3p was found to be the target of the top 3 DECs, including circ-CCDC7, and the stem cell marker gene Pax7 was identified as the target gene of gga-miR-6568-3p. This study demonstrated that exosomal circ-CCDC7/gga-miR-6568-3p/Pax7 accelerates the differentiation of cESCs after early infection with ALV-J.

High-Performance Multi-Level Inverter with Symmetry and Simplification.

This paper presents a high-performance, multilevel inverter with symmetry and simplification. This inverter is a single-phase, seven-level symmetric switched-capacitor inverter based on the concept of the double voltage clamping circuit connected to the half-bridge circuit. Above all, only a single DC power supply is used to achieve a single-phase inverter with seven levels and a voltage gain of three. In addition to analyzing the operating principle of the proposed switched-capacitor multilevel inverter in detail, the stability analysis and controller design are carried out by the state-space averaging method. The feasibility and effectiveness of the proposed structure are validated by some simulated results based on the PSIM simulation tool and by some experiments using FPGA as a control kernel, respectively. However, in this study, the switches were implemented by MOSFETs to meet a high switching frequency. These MOSFETs can be replaced by IGBTs in the motor drive applications so that the used switching frequency can be reduced.

Characterization of Acinetobacter baumannii at a tertiary hospital in Guangzhou: a genomic and clinical study.

Acinetobacter baumannii (AB) infections have become a global public health concern due to the continued increase in the incidence of infection and the rate of resistance to carbapenems. This study aimed to investigate the genomic features of AB strains recovered from a tertiary hospital and assess the clinical implications of the findings. A total of 217 AB strains were collected between 2016 and 2018 at a tertiary hospital in Guangzhou, with 183 (84.33%) being carbapenem-resistant AB (CRAB), with the main mechanism being the carriage of the blaOXA-23 gene. The overall mortality rate of patients caused by such strains was 15.21% (n = 33). Artificial lung ventilation and the use of meropenem were mortality risk factors in AB-infected patients, while KL2 AB infection was negatively associated. Core genome multilocus sequence typing and clustering analysis were performed on the integrated AB genome collection from the NCBI database and this study to illustrate the population structure among China. The results revealed diverse core genome profiles (n = 17) among AB strains from China, and strains from this single hospital exhibited most of the core genome profiles (n = 13), suggesting genetic variability within the hospital and transmission across the country. These findings show that the high transmission potential of the CRAB strains and meropenem usage that confers a selective advantage of CRAB clinically are two major factors that pose significant challenges to the effective clinical management of AB infections. Understanding the genetic features and transmission patterns of clinical AB strains is crucial for the effective control of infections caused by this pathogen.