Xylem embolism induced by freeze-thaw and drought are influenced by different anatomical traits in subtropical montane evergreen angiosperm trees.

Subtropical evergreen broadleaved forests distributed in montane zones of southern China experience seasonal droughts and winter frost. Previously, studies have recognized that xylem anatomy is a determinant of its vulnerability to embolism caused by drought and freezing events. We hypothesized that there is a coordination of xylem resistance to freeze-thaw and drought-induced embolism for the subtropical montane evergreen broadleaved tree species because they are influenced by common xylem structural traits (e.g., vessel diameter). We examined the branch xylem anatomy, resistance to drought-induced embolism (P50), and the percent loss of branch hydraulic conductivity after a severe winter frost (PLCwinter) for 15 evergreen broadleaved tree species in a montane forest in South China. Our results showed that P50 of the studied species ranged from -2.81 to -5.13 MPa, which was not associated with most xylem anatomical properties except for the axial parenchyma-to-vessel connectivity. These tree species differed substantially in PLCwinter, ranging from 0% to 76.41%. PLCwinter was positively related to vessel diameter and negatively related to vessel density, vessel group index, and vessel-to-vessel connectivity, but no coordination with P50. This study suggests that hydraulic adaptation to frost is important to determine the distributional limit of subtropical montane evergreen woody angiosperms.

Genome-wide transcriptome and gene family analysis reveal candidate genes associated with potassium uptake of maize colonized by arbuscular mycorrhizal fungi.

BACKGROUND: Potassium (K) is an essential nutrient for plant growth and development. Maize (Zea mays) is a widely planted crops in the world and requires a huge amount of K fertilizer. Arbuscular mycorrhizal fungi (AMF) are closely related to the K uptake of maize. Genetic improvement of maize K utilization efficiency will require elucidating the molecular mechanisms of maize K uptake through the mycorrhizal pathway. Here, we employed transcriptome and gene family analysis to elucidate the mechanism influencing the K uptake and utilization efficiency of mycorrhizal maize. METHODS AND RESULTS: The transcriptomes of maize were studied with and without AMF inoculation and under different K conditions. AM symbiosis increased the K concentration and dry weight of maize plants. RNA sequencing revealed that genes associated with the activity of the apoplast and nutrient reservoir were significantly enriched in mycorrhizal roots under low-K conditions but not under high-K conditions. Weighted gene correlation network analysis revealed that three modules were strongly correlated with K content. Twenty-one hub genes enriched in pathways associated with glycerophospholipid metabolism, glycerolipid metabolism, starch and sucrose metabolism, and anthocyanin biosynthesis were further identified. In general, these hub genes were upregulated in AMF-colonized roots under low-K conditions. Additionally, the members of 14 gene families associated with K obtain were identified (ARF: 38, ILK: 4, RBOH: 12, RUPO: 20, MAPKK: 89, CBL: 14, CIPK: 44, CPK: 40, PIN: 10, MYB: 174, NPF: 79, KT: 19, HAK/HKT/KUP: 38, and CPA: 8) from maize. The transcript levels of these genes showed that 92 genes (ARF:6, CBL:5, CIPK:13, CPK:2, HAK/HKT/KUP:7, PIN:2, MYB:26, NPF:16, RBOH:1, MAPKK:12 and RUPO:2) were upregulated with AM symbiosis under low-K conditions. CONCLUSIONS: This study indicated that AMF increase the resistance of maize to low-K stress by regulating K uptake at the gene transcription level. Our findings provide a genome-level resource for the functional assignment of genes regulated by K treatment and AM symbiosis in K uptake-related gene families in maize. This may contribute to elucidate the molecular mechanisms of maize response to low K stress with AMF inoculation, and provided a theoretical basis for AMF application in the crop field.

The impact of processing voltage of wire electric discharge machining on the performance of Mo doped V-VO0.2 based Archimedean micro-supercapacitors.

Vanadium oxide-based electrode materials have attracted increasing attention owing to their extraordinary capacitance and prolonged lifespan, excellent conductivity and outstanding electrochemical reversibility. However, the development of vanadium oxide-based integrated electrodes with outstanding capacitive performance is an enduring challenge. This research reports a facile method for structuring 3D Archimedean micro-supercapacitors (AMSCs) composed of Mo doped V-VO0.2 (Mo@V-VO0.2) based integrated electrodes with designable geometric shape, using computer-aided wire electric discharge machining (WEDM). The performance of Mo@V-VO0.2 based AMSCs manufactured by different processing voltages of 60 V, 80 V and 100 V were evaluated. It was found that 80 V is the optimal processing voltage for manufacturing Mo@V-VO0.2 based AMSCs with the best electrochemical performance. This device demonstrates superior capacitive behavior even at an ultra-high scan rate of 50, 000 mV s-1, and achieves a good capacitance retention rate of 94.4% after 2000 cycles. Additionally, the characteristics of electric field distribution were also simulated for optimizing the geometric structure of the microdevices. This WEDM fabrication technique, which is easy, secure, patternable, efficient, economical, eco-friendly, and does not require binders or conductive additives, enables the development of high-capacity 3D pseudocapacitive micro-supercapacitors and demonstrates the great potential for metal oxide synthesis and microdevice manufacturing.

Predictors of Mortality, Drug Resistance, and Determinants among Carbapenem-Resistant Enterobacteriales Infections in Chinese Elderly Patients.

Elderly patients with carbapenem-resistant Enterobacteriales (CRE) infections represent considerable mortality rates. But data on the risk factors for the death of elderly patients following such infection remain limited. We aimed to assess the clinical outcomes, identify mortality-associated risk factors, and determine the antibiotic resistance and resistance genes of isolates for these patients. Hospitalized patients aged ≥65 years with CRE infection from January 2020 to December 2020 were retrospectively reviewed. Isolates identification and molecular characterization of CRE were carried out. Logistic regression analysis was applied to assess the potential factors associated with mortality. Of the 123 elderly patients with CRE infection included in our study, the all-cause mortality rate was 39.8% (49/123). The most prevalent pathogen was carbapenem-resistant Klebsiella pneumoniae (CRKP, 116 of 123). The overall rates of multidrug-resistant (MDR) and extensively drug-resistant (XDR) were 100.0% and 66.7%. All CRE isolates exclusively harbored a singular variant of carbapenemase gene, such as bla KPC-2, bla IMP-4, bla NDM-5, or bla OXA-48, while 98.4% of isolates harbored more than one ß-lactamase gene, of which 106 (86.2%) isolates harbored bla CTX-M, 121 (98.4%) isolates harbored bla TEM, and 116 (94.3%) isolates harbored bla SHV. Multivariable logistic regression analysis revealed that mechanical ventilation (adjusted odds ratio (AOR) = 33.607, 95% confidence interval (CI): 4.176-270.463, P < 0.001), use of tigecycline during hospitalization (AOR = 5.868, 95% CI: 1.318-26.130, P = 0.020), and APACHE II score (AOR = 1.305, 95% CI: 1.161-1.468, P < 0.001) were independent factors associated with increasing the mortality of patients with CRE infection, while admission to intensive care unit (ICU) during hospitalization (AOR = 0.046, 95% CI: 0.004-0.496, P = 0.011) was a protective factor. CRE-infected elderly patients with mechanical ventilation, use of tigecycline during hospitalization, and high APACHE II score were related to poor outcomes. The isolates carried various antibiotic genes and presented high antibiotic resistance. These findings provide crucial guidance for clinicians to devise appropriate strategies for treatment.

The influence of redox potential on phosphorus release from sediments in different water bodies.

Anthropogenic activities have significantly enriched P in sediments of many water bodies, with redox potential (Eh) being a key factor in controlling P adsorption or release.This study evaluates the impact of Eh on P release from sediments in the Weiyuan River, Honghu Lake, and Bao'enqiao Reservoir using reactor experiments. P speciation was further analyzed through SEDEX method. Results show that within an Eh range of -300 mV to +230 mV, more P is released from sediments into the water column. The P fractions CDB-P and Fe(II)-P exhibit the most significant changes, especially in reservoir sediments where ΔCDB-P (85.5 mg/kg) and ΔFe(II)-P (80.6 mg/kg) are the highest among the three water bodies, followed by lake sediments. Additionally, after redox oscillation, the EPC0 of lake and reservoir sediments increased to 16.2 and 18.8 times their initial values, respectively, significantly raising the risk of eutrophication.

Study of corneal and retinal thicknesses at five years after FS-LASIK and SMILE for myopia.

BACKGROUND: This study aimed to observe corneal and retinal thicknesses at 5 years after femtosecond laser-assisted in situ keratomileusis (FS-LASIK) and small incision lenticule extraction (SMILE) for myopia, investigate the effect of epithelial remodeling on refractive status and visual quality, and compare retinal thicknesses among fundus tessellation grades. METHODS: Patients who received FS-LASIK or SMILE 5 years before were enrolled in this cross-sectional study. After 1:1 propensity score matching, each surgical group obtained 177 patients (177 eyes). Examinations including visual acuity, refraction, corneal and retinal thicknesses, corneal higher-order aberrations (HOAs), and fundus photography were performed in this visit at 5 years after surgery. The Quality of Vision (QoV) questionnaire was used to assess visual symptoms and overall satisfaction. Corneal and retinal thicknesses between groups were compared, contributing factors were analyzed, and correlations with postoperative refractive status, HOAs, QoV scores and overall satisfaction were evaluated. RESULTS: The discrepancy of epithelial thickness between central and pericentral zones in FS-LASIK group was larger than that in SMILE group, which was negatively correlated with postoperative spherical equivalent (SE), positively correlated with spherical aberration (all P < 0.05), but not correlated with QoV scores and overall satisfaction (all P > 0.05) in both surgical groups. There was no statistical difference in stromal thickness and total corneal thickness (all P > 0.05). Most annuluses of epithelial and stromal thicknesse were linearly related to preoperative SE (all P < 0.05). The macular thickness, ganglion cell complex thickness, and retinal nerve fiber layer thickness exhibited comparable values between two surgical groups and four fundus tessellation grades, with no significant association observed with postoperative SE (all P > 0.05). CONCLUSION: The tendency that epithelial thickness in central zone was thicker than peripheral zone was more obvious at 5 years after FS-LASIK compared to SMILE. This uneven distribution of epithelial thickness might play a role in myopic regression and the changes in HOAs, especially in patients with high myopia, but it had little effect on patients' subjective visual quality and satisfaction. Retinal thicknesses were not affected by these two surgical methods, and they did not appear to be the clinical indicators for myopic regression or fundus tessellation progression.

Assessing osteoporosis and bone mineral density through 18F-NaF uptake at lumbar spine.

OBJECTIVES: The use of 18F-Sodium fluoride (NaF) PET/CT is established in the detection of metastatic bone disease, yet its utility in osteoporosis remains underexplored. This research aims to assess the variations in 18F-NaF uptake among individuals with differing bone mineral density (BMD) and to examine the relationship between 18F-NaF uptake and BMD. METHODS: In this retrospective study, 199 patients (average age 56 ± 6, comprising 52 males and 147 females) with a history of cancer were analyzed. Each participant underwent both 18F-NaF PET/CT and lumbar dual-energy X-ray absorptiometry (DXA) scans within a span of 7 days. Based on DXA outcomes, patients and their lumbar vertebrae were categorized into normal BMD, osteopenia, and osteoporosis groups. The lumbar 18F-NaF uptake across these groups were compared, and to explore the association between lumbar standardized uptake values (SUV) values and BMD. The efficacy of 18F-NaF uptake in diagnosing osteoporosis or osteopenia was also evaluated. Analysis was conducted using Mann-Whitney U tests, Spearman regression, and receiver operating characteristic (ROC) curve analysis through GraphPad Prism 10.0. RESULTS: A total of 796 lumbar vertebrae from 199 patients were measured. It was observed that osteoporotic patients had significantly lower 18F-NaF uptake than those with osteopenia and normal BMD across the L1-L4 lumbar vertebrae (P < 0.0001). In a vertebra-based analysis, normal BMD vertebrae exhibited the highest maximum SUV(SUVmax) compared to osteopenic (8.13 ± 1.28 vs. 6.61 ± 1.01, P < 0.0001) and osteoporotic vertebrae (8.13 ± 1.28 vs. 4.82 ± 1.01, P < 0.0001). There was a positive correlation between lumbar 18F-NaF uptake and BMD across all vertebrae, with correlation coefficients exceeding 0.5 (range: 0.57-0.8). The area under the ROC curve values were notably high, at 0.96 for osteoporosis and 0.83 for osteopenia diagnosis. CONCLUSION: This study demonstrates distinct 18F-NaF uptake patterns among individuals with varying BMD levels, with a positive correlation between 18F-NaF uptake and BMD. These findings highlight the potential of 18F-NaF PET/CT as a supportive diagnostic method in the management of osteoporosis.

Genome-Wide Analysis of Aquaporins Gene Family in Populus euphratica and Its Expression Patterns in Response to Drought, Salt Stress, and Phytohormones.

Aquaporins (AQPs) play an essential role in membrane water transport during plant responses to water stresses centered on conventional upstream signals. Phytohormones (PHs) regulate plant growth and yield, working with transcription factors to help plants withstand environmental challenges and regulate physiological and chemical processes. The AQP gene family is important, so researchers have studied its function and regulatory system in numerous species. Yet, there is a critical gap the understanding of many of their molecular features, thus our full knowledge of AQPs is far-off. In this study, we undertook a broad examination of the AQP family gene in Populus euphratica via bioinformatics tools and analyzed the expression patterns of certain members in response to drought, salt, and hormone stress. A total of 22 AQP genes were examined in P. euphratica, and were categorized into four main groups, including TIPs, PIPs, SIPs, and NIPs based on phylogenetic analysis. Comparable exon-intron gene structures were found by gene structure examination, and similarities in motif number and pattern within the same subgroup was determined by motif analysis. The PeuAQP gene family has numerous duplications, and there is a distinct disparity in how the members of the PeuAQP family react to post-translational modifications. Abiotic stress and hormone responses may be mediated by AQPs, as indicated by the abundance of stress response elements found in 22 AQP genes, as revealed by the promoter's cis-elements prediction. Expression pattern analysis reveals that selected six AQP genes from the PIP subgroup were all expressed in the leaves, stem, and roots with varying expression levels. Moreover, qRT-PCR analysis discovered that the majority of the selected AQP members were up- or down-regulated in response to hormone treatment and abiotic stress. Remarkably, PeuAQP14 and PeuAQP15 appeared to be highly responsive to drought stress and PeuAQP15 exhibited a high response to salt stress. The foliar application of the phytohormones (SA, IAA, GA3, MeJA, and ABA) were found to either activate or inhibit PeuAQP, suggesting that they may mitigate the effects of water shortage of poplar water stress. The present work enhances our knowledge of the practical roles of AQPs in stress reactions and offers fundamental information for the AQP genes in poplar species. It also highlights a direction for producing new varieties of poplar species with drought, salt, and hormone tolerance and holds substantial scientific and ecological importance, offering a potential contribution to the conservation of poplar species in arid regions.

A novel strategy for spinal cord reconstruction via vascularized allogeneic spinal cord transplantation combine spinal cord fusion.

AIMS: Spinal cord injuries (SCI) pose persistent challenges in clinical practice due to the secondary injury. Drawing from our experience in spinal cord fusion (SCF), we propose vascularized allogeneic spinal cord transplantation (vASCT) as a novel approach for SCI, much like organ transplantation has revolutionized organ failure treatment and vascularized composite-tissue allotransplantation has addressed limb defects. MATERIALS AND METHODS: In this study, 24 dogs were paired and underwent vASCT, with donor spinal cord grafts and polyethylene glycol (PEG) application for SCF. The experimental group (n = 8) received tacrolimus and methylprednisolone, while the control group (n = 4) received only methylprednisolone. Safety and efficacy of vASCT were evaluated through electrophysiology, imaging, and 6-month follow-up. RESULTS: The experimental group showed substantial recovery in hind limb motor function. Imaging revealed robust survival of spinal cord grafts and restoration of spinal cord continuity. In contrast, the control group maintained hind limb paralysis, with imaging confirming spinal cord graft necrosis and extensive defects. Electrophysiologically, the experimental group exhibited restored motor evoked potential signal conduction postoperatively, unlike the control group. Notably, PEG application during vASCT led to signal conduction recovery in intraoperative spinal cord evoked potential examinations for all dogs. CONCLUSION: In the vASCT surgical model, the combination of PEG with tacrolimus has demonstrated the ability to reconstruct spinal cord continuity and restore hind limb motor function in beagles. Notably, a low dose of tacrolimus has also exhibited an excellent anti-immune rejection effect. These findings highlight vASCT's potential promise as a therapeutic strategy for addressing irreversible SCI.

Polymer-locking fusogenic liposomes for glioblastoma-targeted siRNA delivery and CRISPR-Cas gene editing.

In patients with glioblastoma (GBM), upregulated midkine (MDK) limits the survival benefits conferred by temozolomide (TMZ). RNA interference (RNAi) and CRISPR-Cas9 gene editing technology are attractive approaches for regulating MDK expression. However, delivering these biologics to GBM tissue is challenging. Here we demonstrate a polymer-locking fusogenic liposome (Plofsome) that can be transported across the blood-brain barrier (BBB) and deliver short interfering RNA or CRISPR-Cas9 ribonucleoprotein complexes into the cytoplasm of GBM cells. Plofsome is designed by integrating a 'lock' into the fusogenic liposome using a traceless reactive oxygen species (ROS)-cleavable linker so that fusion occurs only after crossing the BBB and entering the GBM tissue with high ROS levels. Our results showed that MDK suppression by Plofsomes significantly reduced TMZ resistance and inhibited GBM growth in orthotopic brain tumour models. Importantly, Plofsomes are effective only at tumour sites and not in normal tissues, which improves the safety of combined RNAi and CRISPR-Cas9 therapeutics.

Pertussis upsurge, age shift and vaccine escape post-COVID-19 caused by ptxP3 macrolide-resistant Bordetella pertussis MT28 clone in China.

OBJECTIVES: China has experienced a notable upsurge in pertussis cases post-COVID-19, alongside an age shift to older children, increased vaccine escape, and a notable rise in the prevalence of macrolide-resistant Bordetella pertussis. Here, we present a genomic epidemiological investigation of these events. METHODS: We performed a retrospective observational study using culture-positive B pertussis isolated in Shanghai, China, from 2016 to 2024. We analysed strain and pertussis epidemiology dynamics by integrating whole-genome sequencing of 723 strains with antimicrobial susceptibility, transcriptomic profile, and clinical data. We compared the genome sequences of Shanghai strains with 6450 Chinese and global strains. RESULTS: From pre-COVID-19 (before December 2019) to post-COVID-19, patients shifted from predominantly infants (90%, 397/442) to a higher proportion of infections in older children (infant: 16%, 132/844), with the share of vaccinated individuals surging from 31% (107/340) to 88% (664/756). The macrolide-resistant Bordetella pertussis prevalence increased from 60% (267/447) to 98% (830/845). The emergence and expansion of a ptxP3-lineage macrolide-resistant clone, MR-MT28, which is uniquely capable of causing substantial infections among older children and vaccinated individuals, was temporally strongly associated with the pertussis upsurge and epidemiological transition. Although MR-MT28 showed increased expression of genes encoding pertussis toxin, it was associated with significantly milder clinical symptoms and a lower hospitalization rate. MR-MT28 likely originated in China around 2016, after acquiring several key mutations, including a novel prn150 allele, and has been detected across multiple regions in China. In addition, 26% (50/195) of MR-MT28 has evolved into predicted Pertactin (PRN)-deficient strains, with an IS481 insertion being the predominant mechanism. DISCUSSION: We report that the post-COVID-19 upsurge of pertussis in China is associated with ptxP3-MR-MT28, and provide evidence that pathogen evolution is likely the primary factor driving + pertussis upsurge, age shift, and vaccine escape. MR-MT28 poses a high risk of global spread and warrants global surveillance.

A Comprehensive Model Outperformed the Single Radiomics Model in Noninvasively Predicting the HER2 Status in Patients with Breast Cancer.

RATIONALE AND OBJECTIVES: This study aimed to develop predictive models based on conventional magnetic resonance imaging (cMRI) and radiomics features for predicting human epidermal growth factor receptor 2 (HER2) status of breast cancer (BC) and compare their performance. MATERIALS AND METHODS: A total of 287 patients with invasive BC in our hospital were retrospectively analyzed. All patients underwent preoperative breast MRI consisting of fat-suppressed T2-weighted imaging, axial dynamic contrast-enhanced MRI, and diffusion-weighted imaging sequences. From these sequences, radiomics features were derived. Three distinct models were established utilizing cMRI features, radiomics features, and a comprehensive model that amalgamated both. The predictive capabilities of these models were assessed using the receiver operating characteristic curve analysis. The comparative performance was then determined through the DeLong test and net reclassification improvement (NRI). RESULTS: In a randomized split, the 287 patients with BC were allotted to either training (234; 46 HER2-zero, 107 HER2-low, 81 HER2-positive) or test (53; 8 HER2-zero, 27 HER2-low, 18 HER2-positive) at an 8:2 ratio. The mean area under the curve (AUCs) for cMRI, radiomics, and comprehensive models predicting HER2 status were 0.705, 0.819, and 0.859 in training set and 0.639, 0.797, and 0.842 in test set, respectively. DeLong's test indicated that the combined model's AUC surpassed the radiomics model significantly (p < 0.05). NRI analysis verified superiority of the combined model over the radiomics for BC HER2 prediction (NRI 25.0) in the test set. CONCLUSION: The comprehensive model based on the combination of cMRI and radiomics features outperformed the single radiomics model in noninvasively predicting the three-tiered HER2 status in patients with BC.

Analysis of Quadriceps Strength and Knee Pain.

OBJECTIVE: To investigate the association of quadriceps strength with the presence of knee pain. DESIGN: This cross-sectional study was based on data from the 1999-2000 to 2001-2002 National Health and Nutrition Examination Survey. SETTING: This was a community-based study. PARTICIPANTS: This study included 2619 adults with complete data for knee pain, quadriceps strength, and covariates. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Self-reported knee pain. RESULTS: This study included 2619 individuals, 1287 (52.66%) of whom were women and 1543 (81.66%) identified as Non-Hispanic White. The mean ±standard deviation age was 62.48±9.71 years. After adjusting for covariates, the odds of knee pain decreased with every 20 N/m increase in quadriceps strength (odds ratio, 0.87; 95% confidence interval, 0.81-0.94). Individuals in the upper quartile of quadriceps strength had lower odds of knee pain than those in the lower quartile (Q4 vs Q1 [reference]: odds ratio, 0.28, 95% confidence interval, 0.15-0.52; Ptrend=.006). Nonlinear analyses indicated L-shaped associations for knee pain. The subgroup analyses showed no significant interactions, except for sex (Pinteraction=.046). The significance of the sex interaction indicated a correlation exclusively in women. CONCLUSIONS: The results demonstrated an inverse association between quadriceps strength and the presence of knee pain. The subgroup analysis by sex showed that this inverse relationship was statistically significant in the women but not in the men subgroup.

Genome-Scale Screening of Saccharomyces cerevisiae Deletion Mutants to Gain Molecular Insight into Tolerance to Mercury Ions.

Mercury (Hg) is a global pollutant and a bioaccumulative toxin that seriously affects the environment. Though increasing information has been obtained on the mechanisms involved in mercury toxicity, there is still a knowledge gap between the adverse effects and action mechanisms, especially at the molecular level. In the current study, we screened a diploid library of Saccharomyces cerevisiae single-gene deletion mutants to identify the nonessential genes associated with increased sensitivity to mercury ions. By genome-scale screening, we identified 64 yeast single-gene deletion mutants. These genes are involved in metabolism, transcription, antioxidant activity, cellular transport, transport facilitation, transport routes, and the cell cycle, as well as in protein synthesis, folding, modification, and protein destination. The concentration of mercury ions was different in the cells of yeast deletion mutants. Moreover, the disruption of antioxidant systems may play a key role in the mercurial toxic effects. The related functions of sensitive genes and signal pathways were further analyzed using bioinformatics-related technologies. Among 64 sensitive genes, 37 genes have human homologous analogs. Our results may provide a meaningful reference for understanding the action mode, cellular detoxification, and molecular regulation mechanisms of mercury toxicity.

Light-induced ligand-to-metal charge transfer of Fe(III)-OR species in organic synthesis.

Light-induced ligand-to-metal charge transfer (LMCT) has been utilized as a powerful strategy in various organic reactions. First-row transition metals, especially iron complexes, show good applications in this process. Fe(III)-Cl and Fe(III)-OR species are two key intermediates involved in the LMCT of iron complexes. This review highlights studies on LMCT of Fe(III)-OR species, including carboxylate-iron and alkoxy-iron species, in organic transformations. Reaction conditions, substrate scope and related mechanisms are discussed.

A pilot clinical risk model to predict polymyxin-induced nephrotoxicity: a real-world, retrospective cohort study.

OBJECTIVES: Polymyxin-induced nephrotoxicity (PIN) is a major safety concern and challenge in clinical practice, which limits the clinical use of polymyxins. This study aims to investigate the risk factors and to develop a scoring tool for the early prediction of PIN. METHODS: Data on critically ill patients who received intravenous polymyxin B or colistin sulfate for over 24 h were collected. Logistic regression with the least absolute shrinkage and selection operator (LASSO) was used to identify variables that are associated with outcomes. The eXtreme Gradient Boosting (XGB) classifier algorithm was used to further visualize factors with significant differences. A prediction model for PIN was developed through binary logistic regression analysis and the model was assessed by temporal validation and external validation. Finally, a risk-scoring system was developed based on the prediction model. RESULTS: Of 508 patients, 161 (31.6%) patients developed PIN. Polymyxin type, loading dose, septic shock, concomitant vasopressors and baseline blood urea nitrogen (BUN) level were identified as significant predictors of PIN. All validation exhibited great discrimination, with the AUC of 0.742 (95% CI: 0.696-0.787) for internal validation, of 0.708 (95% CI: 0.605-0.810) for temporal validation and of 0.874 (95% CI: 0.759-0.989) for external validation, respectively. A simple risk-scoring tool was developed with a total risk score ranging from -3 to 4, corresponding to a risk of PIN from 0.79% to 81.24%. CONCLUSIONS: This study established a prediction model for PIN. Before using polymyxins, the simple risk-scoring tool can effectively identify patients at risk of developing PIN within a range of 7% to 65%.

Molecular epidemiology and genomic features of Bordetella parapertussis in Shanghai, China, 2017-2022.

Background: Pertussis is a highly contagious respiratory illness mainly caused by Bordetella pertussis (BP). Bordetella parapertussis (BPP) can induce symptoms compatible with pertussis, but has been underdiagnosed and underreported. The current pertussis vaccines offer low protection against BPP. Herein, we aim to reveal the epidemiology and genomic evolution of BPP in Shanghai, China. Methods: Children diagnosed with BPP infection from January 2017 to December 2022 in Shanghai, China were enrolled. We performed antimicrobial susceptibility testing (AST), multiple locus variable-number tandem repeat analysis (MLVA), and whole genome sequencing (WGS) analysis. A total of 260 international BPP genomes were chosen for comparison to investigate the genomic diversity and phylogenetic characteristics of Chinese strains within a global context. Results: Sixty patients were diagnosed with BPP infection by culture, with the positive ratio of 3.5‰ (60/17337) for BPP in nasopharyngeal swap samples. The average age of patients was 4.5 ± 0.3 years. BPPs contained four MLVA types including MT6 (65.0%), MT4 (26.7%), untype-1 (6.7%) and MT5 (1.7%), and none of strains showed resistance to macrolides. All strains carried virulence genotype of ptxP37/ptxA13/ptxB3/ptxC3/ptxD3/ptxE3/fim2-2/fim3-10. MT4 and MT5 strains carried prn54, whereas MT6 and untype-1 BPPs expressed prn101. We identified two outbreaks after 2020 caused by MT4 and MT6 strains, each corresponding to distinct WGS-based phylogenetic lineages. The MT4-lineage is estimated to have originated around 1991 and has since spread globally, being introduced to China between 2005 and 2010. In contrast, the MT6-lineage was exclusively identified in China and is inferred to have originated around 2002. Conclusion: We revealed the genomic diversity of BPPs circulating in Shanghai, China, and reported the outbreaks of MT6 and MT4 BPPs after 2020. This is the first report on the emergence and regional outbreak of MT6 BPPs in the world, indicating that continuous surveillance on BPPs are thus required.

Clinical and pathological characteristics of gestational diabetes mellitus with different insulin resistance.

AIMS: To elucidate the clinical and pathological characteristics of gestational diabetes mellitus (GDM) with high and low insulin resistance. METHODS: In total, 1393 GDM and 1001 non-GDM singleton deliveries were included in this study. Insulin resistance subtypes were classified according to the HOMA2-IR value. Clinical data were analyzed using SPSS 26.0. Placenta samples were collected for pathological analysis. RESULTS: Maternal age and fasting glucose were identified as independent risk factors for GDM with high insulin resistance (p < 0.01), while fasting glucose was the sole risk factor for GDM with low insulin resistance (p < 0.001). Fetal distress was associated with both of GDM subtypes (both p < 0.01), while anemia, fetal growth restriction, large for gestational age and intrahepatic cholestasis in pregnancy were related to specific GDM insulin resistance subtype. In addition, GDM with high insulin resistance showed an increase of syncytial knots with down-regulation of PI3K/AKT signaling, while GDM with low insulin resistance showed normal syncytial knot counts and up-regulation of PI3K/AKT signaling. CONCLUSIONS: Our findings provide novel perspectives to the clinical and pathological comprehensions of GDM with high and low insulin resistance, which might facilitate the mechanism study of GDM and its precision pregnancy management.