Effect of Perioperative Blood Transfusion on Prognosis after Radical Resection in Patients with Non-Metastatic Renal Cell Carcinoma: A Retrospective Analysis.

OBJECTIVE: Advancements in medical science have improved non-metastatic renal cell carcinoma (NM-RCC) treatment strategies, but long-term survival is influenced by various factors, including perioperative blood transfusion. This study aims to analyse prognostic factors in patients with NM-RCC after radical nephrectomy. METHODS: From January 2018 to December 2021, a total of 132 patients with NM-RCC after radical nephrectomy were studied. According to 2-year follow-up data, the patients were categorised into case (with poor outcomes, including pneumothorax, renal issues, recurrence or death) and control groups. Data on demographics, clinical characteristics and perioperative blood transfusion were collected, and key prognostic factors were identified through logistic regression. RESULTS: A total of 32 patients with poor prognosis were included in the case group, accounting for 24.24% (32/132), and 100 patients without poor prognosis were included in the control group, accounting for 75.76% (100/132). Tumour stage, tumour size and perioperative blood transfusion were all risk factors for the prognosis of patients, and odds ratio (OR) >1. The above indicators had high predictive value for the prognosis of patients after surgery. CONCLUSIONS: The prognostic factors of patients with NM-RCC after radical nephrectomy include tumour stage, tumour size and perioperative blood transfusion, and each factor had predictive value.

Multimodal deep learning-based drought monitoring research for winter wheat during critical growth stages.

Wheat is a major grain crop in China, accounting for one-fifth of the national grain production. Drought stress severely affects the normal growth and development of wheat, leading to total crop failure, reduced yields, and quality. To address the lag and limitations inherent in traditional drought monitoring methods, this paper proposes a multimodal deep learning-based drought stress monitoring S-DNet model for winter wheat during its critical growth periods. Drought stress images of winter wheat during the Rise-Jointing, Heading-Flowering and Flowering-Maturity stages were acquired to establish a dataset corresponding to soil moisture monitoring data. The DenseNet-121 model was selected as the base network to extract drought features. Combining the drought phenotypic characteristics of wheat in the field with meteorological factors and IoT technology, the study integrated the meteorological drought index SPEI, based on WSN sensors, and deep image learning data to build a multimodal deep learning-based S-DNet model for monitoring drought stress in winter wheat. The results show that, compared to the single-modal DenseNet-121 model, the multimodal S-DNet model has higher robustness and generalization capability, with an average drought recognition accuracy reaching 96.4%. This effectively achieves non-destructive, accurate, and rapid monitoring of drought stress in winter wheat.

Flavomycin restores colistin susceptibility in multidrug-resistant Gram-negative bacteria.

Polymyxin is used as a last resort antibiotics for infections caused by multi-drug resistant (MDR) Gram-negative bacteria and is often combined with other antibiotics to improve clinical effectiveness. However, the synergism of colistin and other antibiotics remains obscure. Here, we revealed a notable synergy between colistin and flavomycin, which was traditionally used as an animal growth promoter and has limited activity against Gram-negative bacteria, using checkerboard assay and time-kill curve analyses. The importance of membrane penetration induced by colistin was assessed by examining the intracellular accumulation of flavomycin and its antimicrobial impact on Escherichia coli (E. coli) strains with truncated lipopolysaccharides. Besides, a mutation in the flavomycin binding site was created to confirm its role in the observed synergy. This synergy is manifested as an augmented penetration of the E. coli outer membrane by colistin, leading to increased intracellular accumulation of flavomycin and enhanced cell killing thereafter. The observed synergy was dependent on the antimicrobial activity of flavomycin, as mutation of its binding site abolished the synergy. In vivo studies confirmed the efficacy of colistin combined with flavomycin against MDR E. coli infections. This study is the first to demonstrate the synergistic effect between colistin and flavomycin, shedding light on their respective roles in this synergism. Therefore, we propose flavomycin as an adjuvant to enhance the potency of colistin against MDR Gram-negative bacteria. IMPORTANCE: Colistin is a critical antibiotic in combating multi-drug resistant Gram-negative bacteria, but the emergence of mobilized colistin resistance (mcr) undermines its effectiveness. Previous studies have found that colistin can synergy with various drugs; however, its exact mechanisms with hydrophobic drugs are still unrevealed. Generally, the membrane destruction of colistin is thought to be the essential trigger for its interactions with its partner drugs. Here, we use clustered regularly interspaced palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) for specifically mutating the binding site of one hydrophobic drug (flavomycin) and show that antimicrobial activity of flavomycin is critical for the synergy. Our results first give the evidence that the synergy is set off by colistin's membrane destruction and operated the final antimicrobial function by its partner drugs.

Comparing the effects of dual-task training and single-task training on walking, balance and cognitive functions in individuals with Parkinson's disease: A systematic review.

BACKGROUND: This systematic review aimed to examine whether dual-task (DT) training was superior to single-task (ST) training in improving DT walking, balance and cognitive function for individuals with Parkinson's disease (PD). METHODS: Literature search was performed in the following electronic databases: PubMed, the Cochrane Library, Web of Science, and Metstr covering inception to May 10, 2023. And in order to facilitate comparison across trials, we calculated the effect size (Hedges' g) of gait, balance, cognitive, and other parameters under both ST and DT conditions, using the mean change score and standard deviation (SD) of change score of the experimental and control groups. Randomized controlled trials that examined the effects of DT motor and cognitive training in individuals with Parkinson's disease were included for this systematic review. RESULTS: A total of 335 participants recruited from six articles (five studies) were involved in this review. In terms of walking function, only double support time and stride time variability showed significant between-group difference (Hedges' g = 0.34, 0.18, respectively). Compared to ST training group, DT training group had a more improvement effect in laboratory balance measurement (Hedges' g = 0.18, 0.25), but no significant improvement in clinical balance measurement. No significant between-group differences were observed, thus its training effect on cognitive function was inconclusive. CONCLUSIONS: The DT training failed to achieve promising results better than ST training in improving DT walking and balance functions for individuals with PD. Any firm conclusion cannot be drawn at present, due to the limited number of eligible publications. Larger sample size and high-quality studies are needed to investigate the effectiveness of DT training in individuals with PD.

A Patient of Spontaneous Bacterial Peritonitis in Hepatitis C Cirrhosis Caused by Gordonia terrae: A Case Report.

Background: Gordonia terrae is an opportunistic pathogen that rarely causes clinical infections. Here, we first report a case of spontaneous bacterial peritonitis in patients with hepatitis C cirrhosis caused by Gordonia terrea. Case Presentation: A 71-year-old male patient was diagnosed with spontaneous bacteria peritonitis secondary to hepatitis C cirrhosis. The result of bacterial culture in ascites was positive, and the pathogenic bacteria was preliminarily identified as the Gordonia genus by matrix-assisted laser desorption ionization-time of flight mass spectrometry. After 16S rRNA sequencing analysis, it was determined to be the Gordonia terrea. Symptoms relieved after treatment with ceftazidime. Conclusion: This case indicates that the clinical infections caused by Gordonia terrea should be brought to the forefront. Accurate and rapid bacterial identification results are highly beneficial to the diagnosis and therapeutic regime.

Elucidating the Role of circTIAM1 in Guangling Large-Tailed Sheep Adipocyte Proliferation and Differentiation via the miR-485-3p/PLCB1 Pathway.

Fat tissue-a vital energy storage organ-is intricately regulated by various factors, including circular RNA, which plays a significant role in modulating fat development and lipid metabolism. Therefore, this study aims to clarify the regulatory mechanism of sheep adipocyte proliferation and differentiation by investigating the involvement of circTIAM1, miR-485-3p, and its target gene PLCB1. Through previous sequencing data, circTIAM1 was identified in sheep adipocytes, with its circularization mechanism elucidated, confirming its cytoplasmic localization. Experimental evidence from RNase R treatment and transcription inhibitors highlighted that circTIAM1 is more stable than linear RNA. Additionally, circTIAM1 promoted sheep adipocyte proliferation and differentiation. Furthermore, bioinformatic analysis demonstrated a robust interaction between miR-485-3p and circTIAM1. Further experiments revealed that miR-485-3p inhibits fat cell proliferation and differentiation by inhibiting PLCB1, with circTIAM1 alleviating the inhibitory effect via competitive binding. In summary, our findings elucidate the mechanism through which circTIAM1 regulates Guangling Large-Tailed sheep adipocyte proliferation and differentiation via the miR-485-3p-PLCB1 pathway, offering a novel perspective for further exploring fat metabolism regulation.

In situ construction of A-site high-entropy perovskites with interfacial CeO2 for a high-performance IT-SOFC air-electrode.

Developing an intermediate-temperature solid oxide fuel cell (IT-SOFC) is one of the most promising ways of achieving carbon neutrality, but its air-electrode is restricted by the conflict between the sluggish catalytic activity and durability. Herein, an A-site high-entropy perovskite composite La0.2Ba0.2Sr0.2Ca0.2Ce0.2-xCoO3-δ-xCeO2 (LBSCCC-CeO2) air-electrode material is fabricated via a one-step self-constructing strategy, which shows excellent oxygen reduction activity and stability due to the high-entropy structure and the synergy effect between LBSCCC and interfacial CeO2. This work provides a new way of fabricating high-performance air-electrodes in IT-SOFCs.

Molecular epidemiology and antimicrobial resistance profiles of Klebsiella pneumoniae isolates from hospitalized patients in different regions of China.

Introduction: The increasing incidence of Klebsiella pneumoniae and carbapenem-resistant Klebsiella pneumoniae (CRKP) has posed great challenges for the clinical anti-infective treatment. Here, we describe the molecular epidemiology and antimicrobial resistance profiles of K. pneumoniae and CRKP isolates from hospitalized patients in different regions of China. Methods: A total of 219 K. pneumoniae isolates from 26 hospitals in 19 provinces of China were collected during 2019-2020. Antimicrobial susceptibility tests, multilocus sequence typing were performed, antimicrobial resistance genes were detected by polymerase chain reaction (PCR). Antimicrobial resistance profiles were compared between different groups. Results: The resistance rates of K. pneumoniae isolates to imipenem, meropenem, and ertapenem were 20.1%, 20.1%, and 22.4%, respectively. A total of 45 CRKP isolates were identified. There was a significant difference in antimicrobial resistance between 45 CRKP and 174 carbapenem-sensitive Klebsiella pneumoniae (CSKP) strains, and the CRKP isolates were characterized by the multiple-drug resistance phenotype.There were regional differences among antimicrobial resistance rates of K. pneumoniae to cefazolin, chloramphenicol, and sulfamethoxazole,which were lower in the northwest than those in north and south of China.The mostcommon sequence type (ST) was ST11 (66.7% of the strains). In addition, we detected 13 other STs. There were differences between ST11 and non-ST11 isolates in the resistance rate to amikacin, gentamicin, latamoxef, ciprofloxacin, levofloxacin, aztreonam, nitrofurantoin, fosfomycin, and ceftazidime/avibactam. In terms of molecular resistance mechanisms, the majority of the CRKP strains (71.1%, 32/45) harbored blaKPC-2, followed by blaNDM (22.2%, 10/45). Strains harboring blaKPC or blaNDM genes showed different sensitivities to some antibiotics. Conclusion: Our analysis emphasizes the importance of surveilling carbapenem-resistant determinants and analyzing their molecular characteristics for better management of antimicrobial agents in clinical use.

A prospective cohort-based artificial intelligence evaluation system for the protective efficacy and immune response of SARS-CoV-2 inactivated vaccines.

BACKGROUND: Novel coronaviruses constitute a significant health threat, prompting the adoption of vaccination as the primary preventive measure. However, current evaluations of immune response and vaccine efficacy are deemed inadequate. OBJECTIVES: The study sought to explore the evolving dynamics of immune response at various vaccination time points and during breakthrough infections. It aimed to elucidate the synergistic effects of epidemiological factors, humoral immunity, and cellular immunity. Additionally, regression curves were used to determine the correlation between the protective efficacy of the vaccine and the stimulated immune response. METHODS: Employing LASSO for high-dimensional data analysis, the study utilised four machine learning algorithms-logistical regression, random forest, LGBM classifier, and AdaBoost classifier-to comprehensively assess the immune response following booster vaccination. RESULTS: Neutralising antibody levels exhibited a rapid surge post-booster, escalating to 102.38 AU/mL at one week and peaking at 298.02 AU/mL at two weeks. Influential factors such as sex, age, disease history, and smoking status significantly impacted post-booster antibody levels. The study further constructed regression curves for neutralising antibodies, non-switched memory B cells, CD4+T cells, and CD8+T cells using LASSO combined with the random forest algorithm. CONCLUSION: The establishment of an artificial intelligence evaluation system emerges as pivotal for predicting breakthrough infection prognosis after the COVID-19 booster vaccination. This research underscores the intricate interplay between various components of immunity and external factors, elucidating key insights to enhance vaccine effectiveness. 3D modelling discerned distinctive interactions between humoral and cellular immunity within prognostic groups (Class 0-2). This underscores the critical role of the synergistic effect of humoral immunity, cellular immunity, and epidemiological factors in determining the protective efficacy of COVID-19 vaccines post-booster administration.

Dynamics of anti-SARS-CoV-2 IgG antibody responses following breakthrough infection and the predicted protective efficacy: A longitudinal community-based population study in China.

OBJECTIVES: To assess the dynamics of the anti-SARS-CoV-2 IgG antibody levels and their efficacy against COVID-19. METHODS: We conducted a longitudinal serological analysis of 852 breakthrough COVID-19 infections among the community-based population in Yichang, China. Anti-SARS-CoV-2 IgG levels were measured by chemiluminescence at approximately 3, 4, and 9 months after infection. A linear mixed model predicted IgG antibody decline over 18 months. The effectiveness of antibodies in preventing symptomatic and severe infections was determined using an existing meta-regression model. RESULTS: IgG antibodies slowly declined after breakthrough infections. Initially high at around 3 months (339.44 AU/mL, IQR: 262.78-382.95 AU/mL), levels remained significant at 9 months (297.74 AU/mL, IQR: 213.22-360.62 AU/mL). The elderly (≥60 years) had lower antibody levels compared to the young (<20 years) (P < 0.001). The protective efficacy of antibodies against symptomatic and severe infections was lower in the elderly (≥60 years) (78.34% and 86.33%) compared to the young (<20 years) (96.56% and 98.75%) after 1 year. CONCLUSION: The study indicated a slow decline in anti-SARS-CoV-2 IgG antibodies, maintaining considerable efficacy for over 1 year. However, lower levels in the elderly suggest reduced protective effects, underscoring the need for age-specific vaccination strategies.

sRNA expression profile of KPC-2-producing carbapenem-resistant Klebsiella pneumoniae: Functional role of sRNA51.

The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) has significant challenges to human health and clinical treatment, with KPC-2-producing CRKP being the predominant epidemic strain. Therefore, there is an urgent need to identify new therapeutic targets and strategies. Non-coding small RNA (sRNA) is a post-transcriptional regulator of genes involved in important biological processes in bacteria and represents an emerging therapeutic strategy for antibiotic-resistant bacteria. In this study, we analyzed the transcription profile of KPC-2-producing CRKP using RNA-seq. Of the 4693 known genes detected, the expression of 307 genes was significantly different from that of carbapenem-sensitive Klebsiella pneumoniae (CSKP), including 133 up-regulated and 174 down-regulated genes. Both the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and Gene Ontology (GO) analysis showed that these differentially expressed genes (DEGs) were mainly related to metabolism. In addition, we identified the sRNA expression profile of KPC-2-producing CRKP for the first time and detected 115 sRNAs, including 112 newly discovered sRNAs. Compared to CSKP, 43 sRNAs were differentially expressed in KPC-2-producing CRKP, including 39 up-regulated and 4 down-regulated sRNAs. We chose sRNA51, the most significantly differentially expressed sRNA in KPC-2-producing CRKP, as our research subject. By constructing sRNA51-overexpressing KPC-2-producing CRKP strains, we found that sRNA51 overexpression down-regulated the expression of acrA and alleviated resistance to meropenem and ertapenem in KPC-2-producing CRKP, while overexpression of acrA in sRNA51-overexpressing strains restored the reduction of resistance. Therefore, we speculated that sRNA51 could affect the resistance of KPC-2-producing CRKP by inhibiting acrA expression and affecting the formation of efflux pumps. This provides a new approach for developing antibiotic adjuvants to restore the sensitivity of CRKP.

Restoring colistin sensitivity in colistin-resistant Salmonella and Escherichia coli: combinatorial use of berberine and EDTA with colistin.

The appearance and prevalence of multidrug-resistance (MDR) Gram-negative bacteria (GNB) have limited our antibiotic capacity to control bacterial infections. The clinical efficacy of colistin (COL), considered as the "last resort" for treating GNB infections, has been severely hindered by its increased use as well as the emergence and prevalence of mobile colistin resistance (MCR)-mediated acquired drug resistance. Identifying promising compounds to restore antibiotic activity is becoming an effective strategy to alleviate the crisis of increasing MDR. We first demonstrated that the combination of berberine (BBR) and EDTA substantially restored COL sensitivity against COL-resistant Salmonella and Escherichia coli. Molecular docking indicated that BBR can interact with MCR-1 and the efflux pump system AcrAB-TolC, and BBR combined with EDTA downregulated the expression level of mcr-1 and tolC. Mechanically, BBR combined with EDTA could increase bacterial membrane damage, inhibit the function of multidrug efflux pump, and promote oxidative damage, thereby boosting the action of COL. In addition, transcriptome analysis found that the combination of BBR and EDTA can accelerate the tricarboxylic acid cycle, inhibit cationic antimicrobial peptide (CAMP) resistance, and attenuate Salmonella virulence. Notably, the combination of BBR and EDTA with COL significantly reduced the bacterial load in the liver and spleen of a mice model infected with Salmonella. Our findings revealed that BBR and EDTA can be used as adjuvants collectively with COL to synergistically reverse the COL resistance of bacteria. IMPORTANCE: Colistin is last-resort antibiotic used to treat serious clinical infections caused by MDR bacterial pathogens. The recent emergence of transferable plasmid-mediated COL resistance gene mcr-1 has raised the specter of a rapid worldwide spread of COL resistance. Coupled with the fact of barren antibiotic development pipeline nowadays, a critical approach is to revitalize existing antibiotics using antibiotic adjuvants. Our research showed that berberine combined with EDTA effectively reversed COL resistance both in vivo and in vitro through multiple modes of action. The discovery of berberine in combination with EDTA as a new and safe COL adjuvant provides a therapeutic regimen for combating Gram-negative bacteria infections. Our findings provide a potential therapeutic option using existing antibiotics in combination with antibiotic adjuvants and address the prevalent infections caused by MDR Gram-negative pathogens worldwide.

Effect of electroacupuncture stimulation of "Sibai"(ST2) and "Quanliao"(SI18) on excitatory neurons of sensorimotor cortex in mice. / 电针"四白"和"颧髎"æ¿€æ´»å°é¼ èº¯ä½“æ„Ÿè§‰è¿åŠ¨çš®å±‚çš„å ´å¥‹æ€§ç¥žç»å ƒ.

OBJECTIVES: To observe the activation state and neuronal types of somatosensory cortex and the primary motor cortex induced by electroacupuncture (EA) stimulation of "Sibai" (ST2) and "Quanliao" (SI18) acupoints in mice. METHODS: Male C57BL/6J mice were randomly divided into blank control and EA groups, with 6 mice in each group. Rats of the EA group received EA stimulation (2 Hz, 0.6 mA) at ST2 and SI18 for 30 minutes. Samples were collected after EA intervention, and immunofluorescence staining was performed to quantify the expression of the c-Fos gene (proportion of c-Fos positive cells) in the somatosensory cortex and primary motor cortex. The co-labelled cells of calcium/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) and gamma-aminobutyric acid (GABA) in the somatosensory cortex and primary motor cortex were observed and counted by using microscope after immunofluorescence staining. Another 10 mice were used to detect the calcium activity of excitatory neurons in the somatosensory cortex and primary motor cortex by fiber photometry. RESULTS: In comparison with the blank control group, the number of c-Fos positive cells, and the proportion of c-Fos and CaMKⅡ co-labelled cells in both the somatosensory cortex and primary motor cortex were significantly increased after EA stimulation (P<0.05). No significant changes were found in the proportion of c-Fos and GABA co-labeled cells in both the somatosensory cortex and primary motor cortex after EA. Results of fiber optic calcium imaging technology showed that the spontaneous calcium activity of excitatory neurons in both somatosensory cortex and primary motor cortex were obviously increased during EA compared with that before EA (P<0.01), and strikingly reduced after cessation of EA compared with that during EA (P<0.05). CONCLUSIONS: Under physiological conditions, EA of ST2 and SI18 can effectively activate excitatory neurons in the somatosensory cortex and primary motor cortex.

Tunable non-polarizing optical bandpass filtering in prism pair coupled planar optical waveguide.

A tunable non-polarizing optical bandpass filter structure, comprising a prism pair coupled planar optical waveguide (POW), is demonstrated, by changing the incident angle of the filter. Experimental measurements show that pass bands for both TM and TE polarized waves are present in the filter simultaneously, and the two passbands overlap on each other. The overlapping of the two passbands can be sustainable for the peak wavelength from 623 to 852 nm as the incident angle of the light tuned within 2°. This POW based optical bandpass filter can be potentially applicable in various fields of optical and laser spectroscopies.

A comparative study of general and severe mycoplasma pneumoniae pneumonia in children.

OBJECTIVES: The increasing prevalence of severe Mycoplasma pneumoniae pneumonia (SMPP) poses a significant threat to the health of children. This study aimed to characterise and assess the outcomes in children with SMPP. METHODS: We retrospectively analysed children hospitalised for M. pneumoniae pneumonia (MPP) between January and December 2022. Retrospectively, demographic, clinical, underlying diseases, laboratory and radiological findings, and treatment outcomes were collected and analysed. Disease severity was defined as severe or general according to the Guideline for diagnosis and treatment of community-acquired pneumonia in children (2019 version). RESULTS: Over a 12-month observation period, 417 children with MPP were enrolled, 50.6% (211/417) of whom had SMPP, with the peak incidence observed in winter. Of the 211 children with SMPP, 210 were treated and discharged with improvement, while one child with congenital heart disease died of cardioembolic stroke. A significantly higher proportion of patients with SMPP had underlying diseases, extrapulmonary complications (myocardial and digestive system involvement), and bacterial co-infection. A total of 25 (12%) children with SMPP received mechanical ventilation. The median duration of mechanical ventilation was 3 days. All children were treated with macrolide antibiotic. A significantly higher proportion of patients with SMPP received antibiotic other than macrolides, methylprednisolone sodium succinate, intravenous immunoglobulin and anticoagulation, compared with patients with general MPP (GMPP). Children with SMPP had significantly higher levels of white blood cells, neutrophil percentage, C-reactive protein, procalcitonin, interferon-γ, interleukin (IL)-2, IL-5, IL-6, IL-8, IL-10 and significantly lower percentages of lymphocytes, monocytes, and natural killer cells, compared with GMPP group. CONCLUSION: Our findings suggest that severely ill children have more pronounced inflammatory reaction and extrapulmonary complications. For effective management of children with SMPP, hormonal, prophylactic, anticoagulant therapy, as well as the use of antibiotics other than macrolides for bacterial co-infections, could be incorporated into treatment regimens.

Legume protein fermented by lactic acid bacteria: Specific enzymatic hydrolysis, protein composition, structure, and functional properties.

In recent years, with increasing emphasis on healthy, green, and sustainable consumption concepts, plant-based foods have gained popularity among consumers. As widely sourced plant-based raw materials, legume proteins are considered sustainable and renewable alternatives to animal proteins. However, legume proteins have limited functional properties, which hinder their application in food products. LAB fermentation is a relatively natural processing method that is safer than chemical/physical modification methods and can enrich the functional properties of legume proteins through biodegradation and modification. Therefore, changes in legume protein composition, structure, and functional properties and their related mechanisms during LAB fermentation are described. In addition, the specific enzymatic hydrolysis mechanisms of different LAB proteolytic systems on legume proteins are also focused in this review. The unique proteolytic systems of different LAB induce specific enzymatic hydrolysis of legume proteins, resulting in the production of hydrolysates with diverse functional properties, including solubility, emulsibility, gelability, and foamability, which are determined by the composition (peptide/amino acid) and structure (secondary/tertiary) of legume proteins after LAB fermentation. The correlation between LAB-specific enzymatic hydrolysis, protein composition and structure, and protein functional properties will assist in selecting legume protein raw materials and LAB strains for legume plant-based food products and expand the application of legume proteins in the food industry.

Promoter regulatory mode evolution enhances the high multidrug resistance of tmexCD1-toprJ1.

Antibiotic resistance could rapidly emerge from acquiring the mobile antibiotic resistance genes, which are commonly evolved from an intrinsic gene. The emergence of the plasmid-borne mobilized efflux pump gene cluster tmexCD1-toprJ1 renders the last-resort antibiotic tigecycline ineffective, although its evolutionary mechanism remains unclear. In this study, we investigate the regulatory mechanisms of the progenitor NfxB-MexCD-OprJ, a chromosomally encoded operon that does not mediate antibiotic resistance in the wild-type version, and its homologs, TNfxB1-TMexCD1-TOprJ1 mediating high-level tigecycline resistance, and TNfxB3-TMexCD3-TOprJ1. Mechanistic studies demonstrated that in nfxB-mexCD-oprJ, MexCD expression was under a weaker promoter, PmexC and inhibited by a strong repressor NfxB. For tmexCD1-toprJ1, TMexCD1 was highly expressed owing to the presence of a strong promoter, PtmexC1, and an inactive suppressor, TNfxB1, with a T39R mutation that rendered it unable to bind to promoter DNA. In tnfxB3-tmexCD3-toprJ1b, TMexCD3 expression was intermediate because of the local regulator TNfxB3, which binds to two inverted repeat sequences of PtmexC. Additionally, TNfxB3 exhibited lower protein expression and weaker DNA binding affinity than its ancestor NfxB, together with their promoter activities difference explaining the different expression levels of tmexCD-toprJ homologs. Distinct fitness burdens on these homologs-carrying bacteria were observed due to the corresponding expression level, which might be associated with their global prevalence. In summary, our data depict the mechanisms underlying the evolution and dissemination of an important mobile antibiotic resistance gene from an intrinsic chromosomal gene.IMPORTANCEAs antibiotic resistance seriously challenges global health, tigecycline is one of the few effective drugs in the pipeline against infections caused by multidrug-resistant pathogens. Our previous work identified a novel tigecycline resistance efflux pump gene cluster tmexCD1-toprJ1 in animals and humans, together with its various variants, a rising clinical concern. Herein, this study focused on how the local regulation modes of tmexCD1-toprJ1 evolved to a highly expressed efflux pump. Through comparative analysis between three tnfxB-tmexCD-toprJ homologs and their progenitor nfxB-mexCD-oprJ, modes, we demonstrated the evolutionary dynamics from a chromosomal silent gene to an active state. We found the de-repression of the local regulator and an increase of the promoter activity work together to promote a high production of drug efflux machines and enhance multidrug resistance. Our findings revealed that TMexCD1-TOprJ1 adopts a distinct evolutionary path to achieve higher multidrug resistance, urgently needing tight surveillance.

Toward Better and Healthier Air Quality: Global PM2.5 and O3 Pollution Status and Risk Assessment Based on the New WHO Air Quality Guidelines for 2021.

To reduce the high burden of disease caused by air pollution, the World Health Organization (WHO) released new Air Quality Guidelines (AQG) on September 22, 2021. In this study, the daily fine particulate matter (PM2.5) and surface ozone (O3) data of 618 cities around the world is collected from 2019 to 2022. Based on the new AQG, the number of attainment days for daily average concentrations of PM2.5 (≤ 15 µg m-3) and O3 (≤ 100 µg m-3) is approximately 10% and 90%, respectively. China and India exhibit a decreasing trend in the number of highly polluted days (> 75 µg m-3) for PM. Every year over 68% and 27% of cities in the world are exposed to harmful PM2.5 (> 35 µg m-3) and O3 (> 100 µg m-3) pollution, respectively. Combined with the United Nations Sustainable Development Goals (SDGs), it is found that more than 35% of the world's cities face PM2.5-O3 compound pollution. Furthermore, the exposure risks in these cities (China, India, etc.) are mainly categorized as "High Risk", "Risk", and "Stabilization". In contrast, economically developed cities are mainly categorized as "High Safety", "Safety", and "Deep Stabilization." These findings indicate that global implementation of the WHO's new AQG will minimize the inequitable exposure risk from air pollution.

Dual contrastive learning for synthesizing unpaired fundus fluorescein angiography from retinal fundus images.

Background: Fundus fluorescein angiography (FFA) is an imaging method used to assess retinal vascular structures by injecting exogenous dye. FFA images provide complementary information to that provided by the widely used color fundus (CF) images. However, the injected dye can cause some adverse side effects, and the method is not suitable for all patients. Methods: To meet the demand for high-quality FFA images in the diagnosis of retinopathy without side effects to patients, this study proposed an unsupervised image synthesis framework based on dual contrastive learning that can synthesize FFA images from unpaired CF images by inferring the effective mappings and avoid the shortcoming of generating blurred pathological features caused by cycle-consistency in conventional approaches. By adding class activation mapping (CAM) to the adaptive layer-instance normalization (AdaLIN) function, the generated images are made more realistic. Additionally, the use of CAM improves the discriminative ability of the model. Further, the Coordinate Attention Block was used for better feature extraction, and it was compared with other attention mechanisms to demonstrate its effectiveness. The synthesized images were quantified by the Fréchet inception distance (FID), kernel inception distance (KID), and learned perceptual image patch similarity (LPIPS). Results: The extensive experimental results showed the proposed approach achieved the best results with the lowest overall average FID of 50.490, the lowest overall average KID of 0.01529, and the lowest overall average LPIPS of 0.245 among all the approaches. Conclusions: When compared with several popular image synthesis approaches, our approach not only produced higher-quality FFA images with clearer vascular structures and pathological features, but also achieved the best FID, KID, and LPIPS scores in the quantitative evaluation.

Microwave hydrothermal sulfuric acid leaching of spent cathode carbon from aluminum electrolysis for high efficiency removal of insoluble calcium fluoride.

Toxic substances, like fluoride salts present in spent cathode carbon (SCC), have been a great risk to the environment and public health. Our approach involves alkali leaching to eliminate soluble fluoride, followed by microwave hydrothermal acid leaching to efficiently remove insoluble CaF2 from SCC. The optimized conditions, including a temperature of 353 K, a solid-liquid ratio of 1:20, and a 60-minute reaction time, resulted in an impressive 95.6 % removal of fluoride from SCC. Various characterization techniques were employed to analyze the composition, micro-morphology, and elemental content of the materials before and after the leaching process. Furthermore, critical process parameters on the leaching separation of insoluble CaF2 during microwave hydrothermal acid leaching were systematically investigated. The study removal mechanism revealed the transformation of insoluble CaF2 in the process of microwave oxidation insertion-hydrothermal acid leaching for SCC. The kinetic characteristics of the two-stage leaching process of CaF2 at different temperatures were analyzed according to the shrinkage kernel model. The results indicate that the two-stage leaching process of CaF2 is affected by mixing control and by diffusion control, severally. The expansion of the graphite flake layer of SCC through oxidative intercalation was identified as a critical process for the thorough removal of CaF2. Microwave hydrothermal acid leaching demonstrated a 17 % improvement over traditional hydrothermal acid leaching within the same reaction time, showcasing a noteworthy enhancement in fluoride removal. Consequently, the microwave oxidizing intercalation-hydrothermal acid leaching treatment of SCC, as explored in this study, offers an effective approach for achieving deep defluoridation of SCC.