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ObjectiveTo explore the relationship between comorbidity and comorbidity pattern prevalence and mobility function among community-dwelling the elderly in Zhejiang province, and to provide a reference basis for the prevention and intervention of comorbidity prevalence in the elderly. MethodsFrom June to December 2022, a multi-stage random sampling method was used to select 7 776 community-dwelling the elderly aged ≥ 60 years old in Zhejiang province for a questionnaire survey. The relationship between comorbidity and comorbidity pattern prevalence and mobility function was analyzed among the 2 445 the elderly who were finally included and participated in the mobility function test. ResultsAmong the 2 445 community-dwelling the elderly in Zhejiang province, 1 250 had comorbidities, with a comorbidity prevalence rate of 51.12%; 533 had cardiovascular-metabolic comorbidity pattern, with a comorbidity prevalence rate of 21.80%; 323 had respiratory system comorbidity pattern, with a comorbidity prevalence rate of 13.20%; 143 had mental-sensory comorbidity pattern, with a comorbidity prevalence rate of 5.84%; and 258 had musculoskeletal joint comorbidity pattern, with a comorbidity prevalence rate of 10.55%. The completion time of the Timed Up and Go (TUG) test for community-dwelling the elderly in Zhejiang province ranged from 5.05 to 59.55 s, with a mean completion time of (11.21 ± 3.15) s; the completion time of the One-Leg Standing with Eyes Closed (OLS-EC) test ranged from 0 to 29 s, with a mean completion time of (3.72 ± 2.72) s; and the number of repetitions completed in the 30-second Chair Stand (CS-30) test ranged from 0 to 30, with a mean number of repetitions of (13.51 ± 3.79). After adjusting for confounding factors such as gender, age, education level, marital status, and place of residence, community-dwelling the elderly with comorbidities in Zhejiang province had longer TUG completion times (β = 0.51, 95%CI: 0.26 – 0.19), and fewer CS-30 repetitions (β = – 0.73, 95%CI: – 1.02 – – 0.45) compared to those without comorbidities; community-dwelling the elderly with cardiovascular-metabolic comorbidity pattern had longer TUG completion times (β = 0.59, 95%CI: 0.30 – 0.23), and fewer CS-30 repetitions (β = – 0.78, 95%CI: – 1.13 – – 0.43) compared to those without cardiovascular-metabolic comorbidities; community-dwelling the elderly with respiratory system comorbidity pattern had fewer CS-30 repetitions (β = – 1.34, 95%CI: – 2.61 – – 0.07) compared to those without respiratory system comorbidities; and community-dwelling the elderly with musculoskeletal joint comorbidity pattern had longer TUG completion times (β = 0.47, 95%CI: 0.08 – 0.02) compared to those without musculoskeletal joint comorbidities. ConclusionThe prevalence of comorbidities among community-dwelling the elderly in Zhejiang province was positively correlated with the risk of individual mobility function decline, and the impact of different comorbidity pattern prevalence on the mobility function of community-dwelling the elderly varies.

Automatic seizure detection using electroen-cephalogram (EEG) can significantly expedite the diagnosis of epilepsy, thereby facilitating prompt treatment and reducing the risk of future seizures and associated complications. While most existing EEG-based epilepsy detection studies employ deep learning models, they often ignore the chronological relationships between different EEG channels. To tackle this limitation, a novel automatic epilepsy detection method is proposed, which leverages path signature and Bidirectional Long Short-Term Memory (Bi-LSTM) neural network with an attention mechanism. The path signature algorithm is used to extract discriminative features for capturing the dynamic dependencies between different channels of EEG, while Bi-LSTM with attention further analyzes the inherent temporal dependencies hidden in EEG signal features. Our method is evaluated on two public EEG databases with different sizes (CHB-MIT and TUEP) and a private database from a local hospital. Two experimental settings are used, i.e., five-fold cross-validation and leave-one-out cross-validation. Experimental results show that our method achieves 99.09%, 95.60%, and 99.87% average accuracies on CHB-MIT, TUEP with 250Hz, and TUEP with 256Hz, respectively. On the private dataset, our method also achieves 99.40% average accuracy, which outperforms other methods. Furthermore, our method exhibits robustness in patients, as demonstrated by the evaluation results of cross-patient experiments.

Being an alien species, Spartina alterniflora has occupied the living space of native animals and plants, causing irreversible damage to the environment. Converting Spartina alterniflora into carbon or its derivatives offers a valuable solution to manage both invasive biomass and an energy shortage. Herein, through a simple activation process, we successfully prepared Spartina alterniflora-derived carbon (SAC) and its N-doped derivative SANC, and used them as metal-free catalysts for an oxygen reduction reaction (ORR). SAC exhibits good electrochemical performance and holds significant potential in catalysis. After N-doping by melamine as a nitrogen source, electronegativity is redistributed in SANC, leading to enhanced performance (a half-wave potential of 0.716 V vs. RHE, and a four-electron transfer pathway with a H2O2 yield of only 2.05%). This work presents a straightforward and cost-effective approach to the usage of obsolete invasive biomass and shows great potential in energy generation.

Objective: this work aimed to investigate the effectiveness of chitosan (CS)/dioleyl phosphatidyl ethanolamine (DOPE) - baicalein (CS/DOPE-BAE) nanohydrogel as a novel drug delivery system for the treatment of periodontitis in rats. Materials and methods: the CS/DOPE-BAE nanohydrogel was synthesized and characterized for its morphology, particle size (PS), drug loading, and release properties. A rat periodontitis model was established, and the rats were randomly assigned to four groups, receiving treatment of normal saline, CS/DOPE blank nanohydrogel, baicalein solution, and CS/DOPE-BAE nanohydrogel through local injection, respectively. Clinical symptoms, periodontal tissue morphology, and the levels of interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), and IL-10 in the periodontal tissue were observed and compared. Results: the CS/DOPE-BAE nanohydrogel exhibited a spherical shape with a PS of approximately 200 nm and a drug loading of 8.6 %. It demonstrated excellent sustained-release properties. The group treated with CS/DOPE-BAE nanohydrogel showed significant improvement in clinical symptoms, such as reduced gingival redness and bleeding in rats, decreased inflammatory cell infiltration, and weakened fibroblast proliferation in the periodontal tissue. Additionally, IL-1β and TNF-α levels were downregulated, while IL-10 level was elevated. Conclusion: the CS/DOPE-BAE nanohydrogel was an effective baicalein delivery system that can inhibit the progression of periodontitis, improve the inflammatory response in periodontal tissue, and deliver promising therapeutic effects.

In order to obtain a lightweight, high-strength, and customizable cellular structure to meet the needs of modern production and life, the mechanical properties of four thickness gradient honeycomb structures were studied. In this paper, four types of honeycomb structure specimens with the same porosity and different Poisson’s ratios were designed and manufactured by using SLA 3D-printing technology, including the honeycomb, square honeycomb, quasi-square honeycomb, and re-entrant honeycomb structures. Based on the plane compression mechanical properties and failure mode analysis of these specimens, the thickness gradient is applied to the honeycomb structure, and four structural forms of the thickness gradient honeycomb structure are formed. The experimental results show that the thickness gradient honeycomb structure exhibits better mechanical properties than the honeycomb structure with a uniform cellular wall thickness. In the studied thickness gradient honeycomb structure, the mechanical properties of the whole structure can be significantly improved by increasing the thickness of cell walls at the upper and lower ends of the structure. The wall thickness, arrangement order, shape, and Poisson’s ratio of the cell all have a significant impact on the mechanical properties of the specimens. These results provide an effective basis for the design and application of cellular structures in the future.

There is an urgent need to find new solutions for the global dilemma of increasing antibiotic resistance in humans and animals. Modifying the performance of existing antibiotics using the nanocarrier drug delivery system (DDS) is a good option considering economic costs, labor costs, and time investment compared to the development of new antibiotics. Numerous studies on nanomedicine carriers that can be used for humans are available in the literature, but relatively few studies have been reported specifically for veterinary pharmaceutical products. Polymer-based nano-DDS are becoming a research hotspot in the pharmaceutical industry owing to their advantages, such as stability and modifiability. This review presents current research progress on polymer-based nanodelivery systems for veterinary antimicrobial drugs, focusing on the role of polymeric materials in enhancing drug performance. The use of polymer-based nanoformulations improves treatment compliance in livestock and companion animals, thereby reducing the workload of managers. Although promising advances have been made, many obstacles remain to be addressed before nanoformulations can be used in a clinical setting. Some crucial issues currently facing this field, including toxicity, quality control, and mass production, are discussed in this review. With the continuous optimization of nanotechnology, polymer-based DDS has shown its potential in reducing antibiotic resistance to veterinary medicines.

Abstract Mycovirus‐mediated hypovirulence has the potential to control fungal diseases. However, the availability of hypovirulence‐conferring mycoviruses for plant fungal disease control is limited as most fungal viruses are asymptomatic. In this study, the virus‐induced gene silencing (VIGS) vector p26‐D4 of Fusarium graminearum gemytripvirus 1 (FgGMTV1), a tripartite circular single‐stranded DNA mycovirus, is successfully constructed to convert the causal fungus of cereal Fusarium head blight (FHB) into a hypovirulent strain. p26‐D4, with an insert of a 75–150 bp fragment of the target reporter transgene transcript in both sense and antisense orientations, efficiently triggered gene silencing in Fusarium graminearum. Notably, the two hypovirulent strains, p26‐D4‐Tri101, and p26‐D4‐FgPP1, obtained by silencing the virulence‐related genes Tri101 and FgPP1 with p26‐D4, can be used as biocontrol agents to protect wheat from a fungal disease FHB and mycotoxin contamination at the field level. This study not only describes the first mycovirus‐derived VIGS system but also proves that the VIGS vector can be used to establish multiple hypovirulent strains to control pathogenic fungi.

Somatostatin interneurons are the earliest born population of cortical inhibitory cells. They are crucial to support normal brain development and function; however, the mechanisms underlying their integration into nascent cortical circuitry are not well understood. In this study, we begin by demonstrating that the maturation of somatostatin interneurons in mouse somatosensory cortex is activity dependent. We then investigated the relationship between activity, alternative splicing, and synapse formation within this population. Specifically, we discovered that the Nova family of RNA-binding proteins are activity-dependent and are essential for the maturation of somatostatin interneurons, as well as their afferent and efferent connectivity. Within this population, Nova2 preferentially mediates the alternative splicing of genes required for axonal formation and synaptic function independently from its effect on gene expression. Hence, our work demonstrates that the Nova family of proteins through alternative splicing are centrally involved in coupling developmental neuronal activity to cortical circuit formation.

BackgroundGrowing evidence has reported an association between multimorbidity and falls and fear of falling (FOF) in older adults, however, the results regarding this association from China are limited. Our study aimed to investigate the association between multimorbidity and falls and FOF in older adults in eastern China.MethodsWe conducted a cross-sectional study in Zhejiang Province, Eastern China, which recruited a provincial representative sample of adults aged ≥ 60 years. A structured questionnaire including demographic characteristics, chronic diseases, history of falls in the past 12 months, and FOF, was administered by all participants. The exposure variable was multimorbidity, which was defined as the presence of two or more chronic diseases and medical conditions in the same individual. The outcomes included a history of falls and FOF. Multivariate logistic regression was used to evaluate the association between multimorbidity and falls and FOF in older adults.ResultsIn total of 7,774 participants were included in the analysis, among whom 3,898 (50.1%) were female, with a mean ± standard deviation age is 72.9 ± 8.4 years. Multimorbidity was associated with the increased risk of falling in older adults [adjusted odds ratio (OR), 1.99; 95% confidence interval (CI):1.55–2.36]. The ORs for having experienced single fall and repeated falls were 1.85 (95% CI: 1.42–2.42) and 3.45 (95% CI: 1.47–6.97), respectively, with multimorbidity compared with those without chronic diseases. The older adults with multimorbidity were more likely to report FOF compared with those without chronic diseases (adjusted OR, 1.49; 95%CI:1.30–1.70). Moreover, the association between multimorbidity and FOF remained significant in the older adults with a history of fall (OR, 1.57; 95%CI:1.04–2.38).ConclusionThe association between multimorbidity and falls and FOF is significant in the Chinese population and the effects of multimorbidity on falls and FOF do not vary according to the frequency and history of falls in older adults.

Fungal endophytes are well-known for their ability to promote plant growth and hinder fungal diseases, including Fusarium head blight (FHB) caused by Fusarium graminearum. This study aimed to characterize the biocontrol efficacy of strain J4-3 isolated from the stem of symptomless wheat collected from Heilongjiang Province, China. It was identified as Epicoccum layuense using morphological characteristics and phylogenetic analysis of the rDNA internal transcribed spacer (ITS) and beta-tubulin (TUB). In a dual culture assay, strain J4-3 significantly inhibited the mycelial growth of F. graminearum strain PH-1 and other fungal pathogens. In addition, wheat coleoptile tests showed that lesion symptoms caused by F. graminearum were significantly reduced in wheat seedlings treated with hyphal fragment suspensions of strain J4-3 compared to the controls. Under field conditions, applying spore suspensions and culture filtrates of strain J4-3 with conidial suspensions of F. graminearum on wheat spikes resulted in the significant biocontrol efficacy of FHB. In addition, wheat seedlings previously treated with spore suspensions of strain J4-3 before sowing successfully resulted in FHB reduction after the application of conidial suspensions of F. graminearum at anthesis. More importantly, wheat seedlings treated with hyphal fragments and spore suspensions of strain J4-3 showed significant increases in wheat growth compared to the controls under greenhouse and field conditions. Overall, these findings suggest that E. layuense J4-3 could be a promising biocontrol agent (BCA) against F. graminearum, causing FHB and a growth-promoting fungus in wheat.

Carbapenemase-producing Enterobacteriaceae (CPE) isolates are recognized as one of the most severe threats to public health. However, the population structure and genetic characteristics of CPE isolates among bloodstream infections (BSIs) are largely unknown. To address this knowledge gap, in this study, we included patients with clinically significant BSIs due to Enterobacterales isolates, recruited from 26 sentinel hospitals in China (2014–2015). CPE isolates were microbiologically and genomically characterized, including their susceptibility profiles, molecular typing, phylogenetic features, and genetic context analysis of carbapenemase-encoding genes. Of the 2569 BSI Enterobacterales isolates enrolled, 42 (1.6%) were carbapenemase-positive. Moreover, among the 2242 investigated isolates, 1111 (49.6%) extended-spectrum β-lactamase (ESBL)-producing isolates were identified in Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), Proteus mirabilis (P. mirabilis), and Klebsiella oxytoca. Whole genome sequencing analysis showed the clonal spread of K. pneumoniae carbapenemase (KPC)-2-producing K. pneumoniae sequence type (ST) 11 and New Delhi metallo-β-lactamase (NDM)-5-producing E. coli ST167 in our collection. Plasmid analysis revealed that carbapenemase-encoding genes were located on multiple plasmids. A high prevalence of biofilm-encoding type 3 fimbriae clusters and yesiniabactin-associated genes was observed in K. pneumoniae isolates. This work demonstrates the high prevalence of ESBLs and the wide dissemination of CPE among BSI isolates in China, which represent real clinical threats. Moreover, our findings first illustrate a more comprehensive genome scenario of CPE isolates among BSIs. The clonal spread of KPC-2-producing K. pneumoniae ST11 and NDM-5-producing E. coli ST167 needs to be closely monitored.

A. baumannii is a common clinical pathogen that often causes pneumonia and bloodstream infections in ICU patients. Sequence types (ST) are used to investigate the distribution and spread of A. baumannii. Biological characteristics such as virulence and resistance may play a role in A. baumannii becoming a specific dominant ST(DST,ST191, ST195 and ST208) strain. To characterize the biological, genetic, and transcriptomic differences between the DST and non-dominant ST(NST,ST462 and ST547,etc.) strains in A. baumannii, we performed several biological experiments and genetic, and transcriptomic analyses. The DST group displayed more resistance ability to desiccation, oxidation, multiple antibiotics, and complement killing than the NST group. However, the latter had higher biofilm formation ability than the former. The genomic analysis showed the DST group exhibited more capsule-related and aminoglycoside-resistant genes. Besides, GO analysis indicated that functions involved in lipid biosynthetic, transport, and the metabolic process were up-regulated in the DST group, while KEGG analysis manifested that the two-component system related to potassium ion transport and pili were down-regulated. In short, resistance to desiccation, oxidation, multiple antibiotics, and serum complement killing are important reasons for the formation of DST. Genes related to capsule synthesis and lipid biosynthesis and metabolism play an important role at the molecular level in the formation of DST.

Abstract It is difficult to remove and eliminate bubbles in microchannels in many devices used in various biomedical fields, such as those needed for microfluidic immunoassays, point-of-care testing, and cell biology evaluations. Accumulated bubbles are associated with a number of negative outcomes, including a decrease in device sensitivity, inaccuracy of analysis results, and even functional failure. Xylem conduits of angiosperm have the ability to remove bubbles in obstructed conduits. Inspired by such an embolism repair mechanism, this paper proposes a bioinspired bubble removal method, which exhibits a prominent ability to dissolve bubbles continuously within a large range of flow rates (2 µL/min–850 µL/min) while retaining the stability and continuity of the flow without auxiliary equipment. Such a method also shows significant bubble removal stability in dealing with Newtonian liquids and non-Newtonian fluids, especially with high viscosity (6.76 Pa s) and low velocity (152 nL/min). Such advantages associated with the proposed bioinspired method reveal promising application prospects in macro/microfluidic fields ranging from 3D printing, implantable devices, virus detection, and biomedical fluid processing to microscale reactor operation and beyond.

Nasopharyngeal carcinoma (NPC) is a kind of malignant tumor. The accurate and automatic segmentation of computed tomography (CT) images of organs at risk (OAR) is clinically significant. In recent years, deep learning models represented by U-Net have been widely applied in medical image segmentation tasks, which can help to reduce doctors’ workload. In the OAR segmentation of NPC, the sizes of the OAR are variable, and some of their volumes are small. Traditional deep neural networks underperform in segmentation due to the insufficient use of global and multi-size information. Therefore, a new SE-Connection Pyramid Network (SECP-Net) is proposed. For extracting global and multi-size information, the SECP-Net designs an SE-connection module and a pyramid structure for improving the segmentation performance, especially that of small organs. SECP-Net also uses an auto-context cascaded structure to further refine the segmentation results. Comparative experiments are conducted between SECP-Net and other recent methods on a private dataset with CT images of the head and neck and a public liver dataset. Five-fold cross-validation is used to evaluate the performance based on two metrics; i.e., Dice and Jaccard similarity. The experimental results show that SECP-Net can achieve SOTA performance in these two challenging tasks.

Electronic noses, or e-noses, refer to systems powered by chemical gas sensors, signal processing, and machine learning algorithms for realizing artificial olfaction. They play a crucial role in various applications for decoding chemical environmental information. Despite decades of advances in gas-sensing technology and artificial intelligence, the reliability and stability of e-nose systems remain challenging, which is also one of the major obstacles that prevent e-noses from large-scale deployment. This paper presents a wide-ranging and structured review of the methods and algorithms developed in the e-nose literature over the past few decades. The review adopts a problem-oriented taxonomy aimed at clarifying the motivations and challenges of different methods and algorithms and their pros and cons. Moreover, several promising research directions in this field have been presented.

Trichomonas vaginalis (T. vaginalis) could cause trichomoniasis through sexual transmission, which was globally distributed. In this study, the prevalence and phylogenetic analyses of T. vaginalis among men in Xinxiang were conducted. From October 2018 to December 2019, a total of 634 male clinical samples were collected, including 254 samples of semen, 43 samples of prostate fluid, and 337 samples of urine. These samples were examined by nested PCR and a total of 32 (5.05%) T. vaginalis-positive samples were detected. Among these samples, the positive rates of T. vaginalis in semen, prostate fluid, and urine were 7.87% (20/254), 4.65% (2/43), and 2.97% (10/337), respectively. Three actin genes were successfully isolated and sequenced from the 32 positive DNA samples, and the analysis of the sequence and phylogenetic tree showed that the three actin gene sequences exhibited 99.7%–100% homology to the published actin gene sequence (EU076580) in NCBI, and the T. vaginalis strains in the three positive samples were identified as genotype E. Our results demonstrate a notable genotype of T. vaginalis in the male population and provide insight into the performance of these genetic markers in the molecular epidemiology of trichomoniasis. However, further studies are needed to research the association between the genotype and the pathogenicity of T. vaginalis.

Geological hazards can cause significant harm to the construction and maintenance of reef infrastructure projects in the Xisha Sea area. This study uses high-resolution multichannel earthquake data, single-channel seismic profiles, and multi-beam survey data to identify and analyze the geological hazards in the Xisha Sea area since the Miocene. Based on the geophysical data interpretation, the destructive geological disaster factors that are active, such as active faults, shallow gas, diapers, landslides, multistage scarps (steps), scouring troughs, and canyons, as well as the restrictive geological disaster factors without activity ability, such as buried paleochannels, pockmarks, reefs, and undersea volcanoes, are identified and analyzed. This paper discusses the causes and hazards of geological hazards and, for the first time, draws a comprehensive plane layout of the geological hazards. The above analysis demonstrates that the scarps are mainly located around the atolls or platforms, and the slope of the southeast seabed topography is significantly higher than that of the northwest. There are seven medium and large landslides, mainly located around Yongxing Plateau and Yongle Plateau, caused by gravity and faulting. Shallow gas is mainly developed in the southern part of the North Reef and is indicated by diaper structures, faults, and gas chimneys. A series of shallow faults are developed in the study area, mainly steep normal faults. The scouring troughs are primarily distributed near the Yongxing Platform, Zhongjian North Platform, and Huaguang Platform. Submarine canyons are primarily located in the northern and southern parts of the Shidao Platform. Affected by multiple factors such as hydrodynamic conditions, the stability of sedimentary layers, and sediment supply, the scour degree varies, with the general depth ranging from several meters to several hundred meters. Underwater infrastructure in the study area should not be constructed in areas with active and destructive geological hazards. The results of this study can serve as a guide for further exploration in the Xisha area and disaster prevention and mitigation during construction activity in the area.

Rieske nonheme iron aromatic ring-hydroxylating oxygenases (RHOs) play pivotal roles in determining the substrate preferences of polycyclic aromatic hydrocarbon (PAH) degraders. However, their potential to degrade high molecular weight PAHs (HMW-PAHs) has been relatively unexplored. NarA2B2 is an RHO derived from a thermophilic Hydrogenibacillus sp. strain N12. In this study, we have identified four “hotspot” residues (V236, Y300, W316, and L375) that may hinder the catalytic capacity of NarA2B2 when it comes to HMW-PAHs. By employing structure-guided rational enzyme engineering, we successfully modified NarA2B2, resulting in NarA2B2 variants capable of catalyzing the degradation of six different types of HMW-PAHs, including pyrene, fluoranthene, chrysene, benzo[a]anthracene, benzo[b]fluoranthene, and benzo[a]pyrene. Three representative variants, NarA2B2W316I, NarA2B2Y300F-W316I, and NarA2B2V236A-W316I-L375F, not only maintain their abilities to degrade low-molecular-weight PAHs (LMW-PAHs) but also exhibited 2 to 4 times higher degradation efficiency for HMW-PAHs in comparison to another isozyme, NarAaAb. Computational analysis of the NarA2B2 variants predicts that these modifications alter the size and hydrophobicity of the active site pocket making it more suitable for HMW-PAHs. These findings provide a comprehensive understanding of the relationship between three-dimensional structure and functionality, thereby opening up possibilities for designing improved RHOs that can be more effectively used in the bioremediation of PAHs. [ABSTRACT FROM AUTHOR]

To investigate the virulence of capsular polysaccharide export protein (Wza) in carbapenem-resistant Acinetobacter baumannii and its effect on capsule formation. wza gene knockout and complementation strains were constructed, and changes in bacterial virulence were observed using in vitro adhesion, antiserum complement killing, anti-oxidation experiments, and infections in Galleria mellonella and mice. The effect of wza knockout on the genes wzb and wzc and wzi were assessed by RT-PCR. We successfully constructed wza knockout and complementation strains. Compared with wild-type (WT) strains, wza knockout strains displayed lower adhesion to A549 cells (p = 0.044), lower antiserum complement killing ability (p = 0.001), and lower mortality of G. mellonella (p = 0.010) and mice (p = 0.033). Expression levels of wzb, wzc and wzi were decreased in wza knockout strains. The antioxidant capacity of Wza knockout bacteria was only slightly decreased. Complementation of the wza gene returned the adhesion ability, antiserum complement killing ability, and mortality of G. mellonella and mice to WT levels. Expression of wzb, wzc and wzi was also returned to WT levels following wza complementation. The results clearly demonstrate that Wza is toxic. Wza affects the expression of other proteins of the Wzy capsule polysaccharide synthesis pathway, which affects the assembly, export, and extracellular fixation of capsular polysaccharide, resulting in synergistic effects that decrease bacterial virulence.

BackgroundCarbapenem-resistant Acinetobacter baumannii (CRAB) is a common cause of ventilator-associated pneumonia (VAP) in intensive care unit (ICU) patients, but its infection and colonization state are difficult to distinguish. If the judgment is wrong, it may aggravate the abuse of antibiotics and further accelerate the evolution of drug resistance. We sought to provide new clues for the diagnosis, pathogenesis and treatment of CRAB VAP based on lower respiratory tract (LRT) microbiota.MethodsA prospective study was conducted on patients with mechanical ventilation from July 2018 to December 2019 in a tertiary hospital. Multi-genomics studies (16S rRNA amplicon, metagenomics, and whole-genome sequencing [WGS]) of endotracheal deep aspirate (ETA) were performed.ResultsFifty-two ICU patients were enrolled, including 24 with CRAB VAP (CRAB-I), 22 with CRAB colonization (CRAB-C), and six CRAB-negative patients (infection-free) (CRAB-N). Diversity of pulmonary microbiota was significantly lower in CRAB-I than in CRAB-C or CRAB-N (mean Shannon index, 1.79 vs. 2.73 vs. 4.81, P < 0.05). Abundances of 11 key genera differed between the groups. Acinetobacter was most abundant in CRAB-I (76.19%), moderately abundant in CRAB-C (59.14%), and least abundant in CRAB-N (11.25%), but its interactions with other genera increased in turn. Metagenomics and WGS analysis showed that virulence genes were more abundant in CRAB-I than in CRAB-C. Multi-locus sequence typing (MLST) of 46 CRAB isolates revealed that the main types were ST208 (30.43%) and ST938 (15.22%), with no difference between CRAB-I and CRAB-C.ConclusionLower respiratory tract microbiota dysbiosis including elevated relative abundance of Acinetobacter and reduced bacterial interactions, and virulence enrichment may lead to CRAB VAP.

An amendment to this paper has been published and can be accessed via the original article.

We aimed to clarify the epidemiologic and clinical importance of evolutionary events that occurred in carbapenem-resistant Klebsiella pneumoniae (CRKP). We collected 203 CRKP causing bloodstream infections in a tertiary hospital in China during 2013–2017. We detected a subclonal shift in the dominant clone sequence type (ST) 11 CRKP in which the previously prevalent capsular loci (KL) 47 had been replaced by KL64 since 2016. Patients infected with ST11-KL64 CRKP had a significantly higher 30-day mortality rate than other CRKP-infected patients. Enhanced virulence was further evidenced by phenotypic tests. Phylogenetic reconstruction demonstrated that ST11-KL64 is derived from an ST11-KL47–like ancestor through recombination. We identified a pLVPK-like virulence plasmid carrying rmpA and peg-344 in ST11-KL64 exclusively from 2016 onward. The pLVPK-like–positive ST11-KL64 isolates exhibited enhanced environmental survival. Retrospective screening of a national collection identified ST11-KL64 in multiple regions. Targeted surveillance of this high-risk CRKP clone is urgently needed.

Small RNA (sRNA) plays a central role in RNA silencing in fungi. The genome of Fusarium graminearum gemytripvirus 1 (FgGMTV1) is comprised of three DNA segments: DNA-A, DNA-B, and DNA-C. DNA-A and DNA-B are associated with fungal growth and virulence reduction. To elucidate the role of RNA silencing during the interactions of fungi and viruses, the sRNA profiles of F. graminearum in association with FgGMTV1 were established, using an FgGMTV1-free library (S-S), a library for infection with the DNA-A and DNA-B segments (S-AB), and a library for infection with the DNA-A, DNA-B, and DNA-C segments (S-ABC). A large amount of virus-derived sRNA (vsiRNA) was detected in the S-AB and S-ABC libraries, accounting for 9.9% and 13.8% of the total sRNA, respectively, indicating that FgGMTV1 triggers host RNA silencing. The total numbers of sRNA reads differed among the three libraries, suggesting that FgGMTV1 infection interferes with host RNA silencing. In addition, the relative proportions of the different sRNA lengths were altered in the S-AB and S-ABC libraries. The genome distribution patterns of the mapping of vsiRNA to DNA-A and DNA-B in the S-AB and S-ABC libraries were also different. These results suggest the influence of DNA-C on host RNA silencing. Transcripts targeted by vsiRNAs were enriched in pathways that included flavin adenine dinucleotide binding, protein folding, and filamentous growth.

Fungal viruses are widespread in fungi infecting plants, insects and animals. High-throughput sequencing has rapidly led to the discovery of fungal viruses. However, the interactive exploration between fungi and viruses is relatively limited. RNA silencing is the fundamental antivirus pathway in fungi. Fusarium graminearum small RNA (sRNA) pattern was regulated by Fusarium graminearum hypovirus 1 (FgHV1) infection, indicating the activation of RNA silencing in virus defense. In this study, we focused on the function of an uncharacterized protein sized at 20 kD (p20) encoded by FgHV1. In the agro-infiltration assay, p20 was identified as a novel fungal RNA silencing suppressor. p20 can block systemic RNA silencing signals besides local RNA silencing suppression. We further elucidated the RNA silencing suppression mechanism of p20. The single-strand sRNA, instead of double-strand sRNA, can be incorporated by p20 in electrophoretic mobility shift assay. p20 binds sRNA originating from virus and non-virus sources in a non-sequence-specific manner. In addition, The F. graminearum 22 and 23-nt sRNA abundance and pathways related to RNA processing and redox regulation were regulated by p20. Our study revealed the first fungal virus-encoded RNA silencing suppressor with sRNA binding capability.

The emergence of carbapenem resistance (CR) caused by hydrolytic enzymes called carbapenemases has become a major concern worldwide. So far, CR genes have been widely detected in various bacteria. However, there is no report of CR gene harboring Comamonas thiooxydans. We first isolated a strain of an IMP-8-producing C. thiooxydans from a patient with urinary tract infection in China. Species identity was determined using MALDI-TOF MS analysis and carbapenemase-encoding genes were detected using PCR. The complete genomic sequence of C. thiooxydans was identified using Illumina Novaseq and Oxford Nanopore PromethION. Antimicrobial susceptibility analysis indicated that the C. thiooxydans strain ZDHYF418 was susceptible to imipenem, intermediate to meropenem, and was resistant to aztreonam, fluoroquinolones, and aminoglycosides. The blaIMP–8 gene was chromosomally located, and was part of a Tn402-like class 1 integron characterized by the following structure: DDE-type integrase/transposase/recombinase-tniB-tniQ-recombinase family protein-aac(6′)-Ib-cr-blaIMP–8-intI1. Phylogenetic analysis demonstrated that the closest relative of ZDHYF418 is C. thiooxydans QYY (accession number: CP053920.1). We detected 330 SNP differences between ZDHYF418 and C. thiooxydans QYY. Strain QYY was isolated from activated sludge in Jilin province, China in 2015. In summary, we isolated a strain of C. thiooxydans that is able to produce IMP-8 and a novel blaOXA. This is the first time that a CR gene has been identified in C. thiooxydans. The occurrence of the strain needs to be closely monitored.

Daily rhythms are disrupted in patients with mood disorders. The lateral habenula (LHb) and dorsal raphe nucleus (DRN) contribute to circadian timekeeping and regulate mood. Thus, pathophysiology in these nuclei may be responsible for aberrations in daily rhythms during mood disorders. Using the 15-day chronic social defeat stress (CSDS) paradigm and in vitro slice electrophysiology, we measured the effects of stress on diurnal rhythms in firing of LHb cells projecting to the DRN (cellsLHb→DRN) and unlabeled DRN cells. We also performed optogenetic experiments to investigate if increased firing in cellsLHb→DRN during exposure to a weak 7-day social defeat stress (SDS) paradigm induces stress-susceptibility. Last, we investigated whether exposure to CSDS affected the ability of mice to photoentrain to a new light-dark (LD) cycle. The cellsLHb→DRN and unlabeled DRN cells of stress-susceptible mice express greater blunted diurnal firing compared to stress-näive (control) and stress-resilient mice. Daytime optogenetic activation of cellsLHb→DRN during SDS induces stress-susceptibility which shows the direct correlation between increased activity in this circuit and putative mood disorders. Finally, we found that stress-susceptible mice are slower, while stress-resilient mice are faster, at photoentraining to a new LD cycle. Our findings suggest that exposure to strong stressors induces blunted daily rhythms in firing in cellsLHb→DRN, DRN cells and decreases the initial rate of photoentrainment in susceptible-mice. In contrast, resilient-mice may undergo homeostatic adaptations that maintain daily rhythms in firing in cellsLHb→DRN and also show rapid photoentrainment to a new LD cycle.

Primary retroperitoneal teratomas are rare, representing only 1%–11% of primary retroperitoneal neoplasms. They typically present as an asymptomatic abdominal mass but can grow to enormous size. The majority of these are benign mature and immature teratomas. We found a large mass in the left abdomen of the child. According to examinations (CT, Ultrasound, Tumor markers, etc.), it was considered to be benign, which was treated by laparoscopic surgery. However, CT revealed that part of the diaphragm was invaded, increasing the difficulty of our operation and intraoperatively confirmed the invasion of the left diaphragm. A frozen section and final histopathologic examination also revealed mature cystic teratoma. This case study highlights the importance of pre-operative imaging and tumor markers. Under the premise of ensuring the safety of the child, laparoscopic procedures have resulted in decreased tissue trauma and accelerated postoperative recovery.

Botryosphaeria dothidea is, globally, one of the most economically important phytopathogenic fungi worldwide, causing the canker and dieback of fruit trees. An increasing number of viruses infecting B. dothidea have lately been reported, several of which could confer hypovirulence. In this study, isolated from strain ZM170285-1 of B. dothidea, a novel double-stranded RNA (dsRNA) mycovirus, tentatively named Botryosphaeria dothidea partitivirus 2 (BdPV2), was identified well. The BdPV2 harbored three dsRNA segments (1–3) with lengths of 1751, 1568, and 1198 bp, which encoded an RNA-dependent RNA polymerase (RdRp), a capsid protein (CP), and a hypothetical protein of unknown function, respectively. BLASTp searches revealed that the predicted protein sequences of dsRNA1 and dsRNA2 had the highest identities (74.95% and 61.01%) with the corresponding dsRNAs of Penicillium stoloniferum virus S (PsV-S), whereas dsRNA3 shared the highest identity (32.95%) with the dsRNA3 of Aspergillus ochraceous virus 1 (AoV1). Phylogenetic analysis indicated that BdPV2 belonged to the Gammapartitivirus genus and Partitiviridae family. To our knowledge, this is the first report of a Gammapartitivirus in B. dothidea.

ABSTRACT The emergence and spread of carbapenem-resistant hypervirulent Klebsiella pneumoniae sequence type 11 (ST11-CR-HvKP) in China are a great concern in the public health community. However, the underlying mechanism that enables its wide dissemination in China remains unclear. Here, we investigated the prevalence of carriage of carbapenemase-producing Enterobacteriaceae (CPE) among inpatients with diarrhea in a teaching hospital over 1 year to identify ST11-CR-HvKP reservoirs and to understand the genetic background and plasmid profiles of these pathogens. As assessed by stool analysis, the CPE colonization rate (12.4%) among the inpatients with diarrhea was high (12.4%). Antibiotic exposure, surgical history, and CPE positivity were correlated. Genomic investigation of 65 carbapenem-resistant K. pneumoniae isolates indicated a shared bacterial population in various wards. According to maximum likelihood phylogenetic tree analysis, these isolates were partitioned into three major clades. Analysis of the wzi locus revealed three different K types (KL105, KL47, and K64) among the ST11 isolates, indicating the genetic diversity of these isolates. Genetic and sequence mapping revealed the complexity of virulence and resistance plasmid sets harbored by the isolates. These observations indicate that the dissemination of resistant bacteria is more complex than initially anticipated and possibly involves multiple K. pneumoniae ST11 lineages and a variety of virulence plasmids. Collectively, we show for the first time that stool may be a source of ST11-CR-HvKP isolates. Furthermore, the findings reveal the silent dissemination of ST11-CR-HvKP bacteria in Zhejiang Province, China. Future investigations are warranted to determine the association between rectal colonization by ST11-CR-HvKP and clinical infections. IMPORTANCE China has been experiencing a rapid increase in the number of nosocomial infections caused by carbapenem-resistant Klebsiella pneumoniae ST11 (ST11-CRKP) for decades. The emergence of hypervirulent ST11-CRKP (ST11-CR-HvKP) strains is expected to become a serious public health issue in China, considering that carbapenem resistance and virulence have converged in an epidemic clone. K. pneumoniae strains that colonize the human intestinal tract may become a reservoir of virulence and carbapenemase-encoding genes. Here, we first characterized the genotypes and antimicrobial phenotypes of ST11-CR-HvKP strains isolated from diarrheal stool samples of inpatients in Zhejiang Province, China. Active surveillance approaches based on the findings of the present study should be implemented, particularly in intensive care units, to combat the spread of ST11-CR-HvKP and to improve treatment.