Search

Abstract Intestinal fibrosis is the primary cause of disability in patients with Crohn’s disease (CD), yet effective therapeutic strategies are currently lacking. Here, we report a multiomics analysis of gut microbiota and fecal/blood metabolites of 278 CD patients and 28 healthy controls, identifying characteristic alterations in gut microbiota (e.g., Lachnospiraceae, Ruminococcaceae, Muribaculaceae, Saccharimonadales) and metabolites (e.g., L-aspartic acid, glutamine, ethylmethylacetic acid) in moderate-severe intestinal fibrosis. By integrating multiomics data with magnetic resonance enterography features, putative links between microbial metabolites and intestinal fibrosis-associated morphological alterations were established. These potential associations were mediated by specific combinations of amino acids (e.g., L-aspartic acid), primary bile acids, and glutamine. Finally, we provided causal evidence that L-aspartic acid aggravated intestinal fibrosis both in vitro and in vivo. Overall, we offer a biologically plausible explanation for the hypothesis that gut microbiota and its metabolites promote intestinal fibrosis in CD while also identifying potential targets for therapeutic trials.

Objectives: The aim of this study was to characterise the first complete genome of Porphyromonas pogonae strain PP01-1 of human origin in China. Methods: The Illumina NovaSeq 6000 (200X coverage) and Nanopore MinION platforms (100× coverage) were used for genome sequencing. A de novo hybrid assembly of short Illumina reads and long MinION reads was performed using Unicycler (v.0.5.0). Genome annotation of PP01-1 was performed using the prokaryotic gene-prediction tool Prokka1.14.6. The genome was further analysed using several bioinformatics tools, including ResFinder, VFDB, VirulenceFinder, Type Strain Genome Server, AntiSMASH, PathogenFinder, MobileElementfinder, CRISPRFinder, and IslandViewer. Results: The assembled circular genome of P. pogonae strain PP01-1 was 2 916 423 bp in length, with a GC content of 41.0%, and no plasmid sequence was detected. A total of 2399 coding sequences were predicted by Prokka. PP01-1 harbours antimicrobial resistance genes blaOXA-347 (β-lactamase resistance), tet(Q) (tetracycline resistance), and floR (chloramphenicol and florfenicol resistance). Conclusions: Here, we are the first to report the complete genome of P. pogonae strain PP01-1 of human origin. In this strain, we first identified blaOXA-347 and tet(Q) in P. pogonae, which will pave the way for further analysis that could identify the potential mechanism of antibiotic resistance and virulence factors in P. pogonae.

Abstract Background H2S imbalances in the intestinal tract trigger Crohn's disease (CD), a chronic inflammatory gastrointestinal disorder characterized by microbiota dysbiosis and barrier dysfunction. However, a comprehensive understanding of H2S generation in the gut, and the contributions of both microbiota and host to systemic H2S levels in CD, remain to be elucidated. This investigation aimed to enhance comprehension regarding the sulfidogenic potential of both the human host and the gut microbiota. Results Our analysis of a treatment-naive CD cohorts' fecal metagenomic and biopsy metatranscriptomic data revealed reduced expression of host endogenous H2S generation genes alongside increased abundance of microbial exogenous H2S production genes in correlation with CD. While prior studies focused on microbial H2S production via dissimilatory sulfite reductases, our metagenomic analysis suggests the assimilatory sulfate reduction (ASR) pathway is a more significant contributor in the human gut, given its high prevalence and abundance. Subsequently, we validated our hypothesis experimentally by generating ASR-deficient E. coli mutants ∆cysJ and ∆cysM through the deletion of sulfite reductase and L-cysteine synthase genes. This alteration significantly affected bacterial sulfidogenic capacity, colon epithelial cell viability, and colonic mucin sulfation, ultimately leading to colitis in murine model. Further study revealed that gut microbiota degrade sulfopolysaccharides and assimilate sulfate to produce H2S via the ASR pathway, highlighting the role of sulfopolysaccharides in colitis and cautioning against their use as food additives. Conclusions Our study significantly advances understanding of microbial sulfur metabolism in the human gut, elucidating the complex interplay between diet, gut microbiota, and host sulfur metabolism. We highlight the microbial ASR pathway as an overlooked endogenous H2S producer and a potential therapeutic target for managing CD. Video Abstract

BackgroundExtensively drug-resistant Acinetobacter baumannii (XDRAB) has become a significant pathogen in hospital environments, particularly in intensive care units (ICUs). XDRAB’s resistance to conventional antimicrobial treatments and ability to survive on various surfaces pose a substantial threat to patient health, often resulting in severe infections such as ventilator-associated pneumonia (VAP) and bloodstream infections (BSI).MethodsWe retrospectively analyzed clinical data from 559 patients with XDRAB infections admitted to Jinhua Central Hospital between January 2021 and December 2023. Patients were randomly divided into a training set (391 cases) and a testing set (168 cases). Variables were selected using Lasso regression and logistic regression analysis, and a predictive model was constructed and validated internally and externally. Model performance and clinical utility were evaluated using the Hosmer-Lemeshow test, C-index, ROC curve, decision curve analysis (DCA), and clinical impact curve (CIC).ResultsLasso regression analysis was used to screen 35 variables, selecting features through 10-fold cross-validation. We chose lambda.1se=0.03450 (log(lambda.1se)=-3.367), including 10 non-zero coefficient features. These features were then included in a multivariate logistic regression analysis, identifying 8 independent risk factors for XDRAB infection: ICU stay of 1-7 days (OR=3.970, 95%CI=1.586-9.937), ICU stay >7 days (OR=12.316, 95%CI=5.661-26.793), hypoproteinemia (OR=3.249, 95%CI=1.679-6.291), glucocorticoid use (OR=2.371, 95%CI=1.231-4.564), urinary catheterization (OR=2.148, 95%CI=1.120-4.120), mechanical ventilation (OR=2.737, 95%CI=1.367-5.482), diabetes mellitus (OR=2.435, 95%CI=1.050-5.646), carbapenem use (OR=6.649, 95%CI=2.321-19.048), and β-lactamase inhibitor use (OR=4.146, 95%CI=2.145-8.014). These 8 factors were used to construct a predictive model visualized through a nomogram. The model validation showed a C-index of 0.932 for the training set and 0.929 for the testing set, with a Hosmer-Lemeshow test p-value of 0.47, indicating good calibration. Furthermore, the DCA curve demonstrated good clinical decision-making performance, and the CIC curve confirmed the model’s reliable clinical impact.ConclusionRegression analysis identified ICU stay duration, hypoproteinemia, glucocorticoid use, urinary catheterization, mechanical ventilation, diabetes mellitus, carbapenem use, and β-lactamase inhibitor use as independent risk factors for XDRAB infection. The corresponding predictive model demonstrated high accuracy and stability.

Abstract Background Pasteurella multocida is a zoonotic pathogen that mainly causes local skin and soft tissue infections in the human body through cat and dog bites. It rarely causes bacteraemia (or sepsis) and meningitis. We reported a case of septic shock and meningitis caused by P. multocida in a patient without a history of cat and dog bites. Case presentation An 84-year-old male patient was urgently sent to the emergency department after he was found with unclear consciousness for 8 h, accompanied by limb tremors and urinary incontinence. In the subsequent examination, P. multocida was detected in the blood culture and wound secretion samples of the patient. However, it was not detected in the cerebrospinal fluid culture, but its DNA sequence was detected. Therefore, the patient was clearly diagnosed with septic shock and meningitis caused by P. multocida. The patient had no history of cat or dog contact or bite. The patient was subsequently treated with a combination of penicillin G, doxycycline, and ceftriaxone, and he was discharged after 35 days of hospitalisation. Conclusion This report presented a rare case of septic shock and meningitis caused by P. multocida, which was not related to a cat or dog bite. Clinical doctors should consider P. multocida as a possible cause of sepsis or meningitis and should be aware of its potential seriousness even in the absence of animal bites.

During the later reproductive period of rice growth, the chlorophyll in the leaves degraded, accompanied by the nitrogen (N) transportation from leaves to panicle, resulting in a change in leaf color from green to yellow. This study aimed to investigate the effects of exogenous N supply on leaf color-changing, N accumulation, N transportation, and N loss of indica-japonica hybrid rice during the grain-filling stage. Two indica-japonica hybrid rice cultivars, Chunyou 167 (CY167) and Chunyou 927 (CY927), which exhibited significant differences in leaf color-changing during the grain-filling stage, were selected as materials for field experiment and hydroponic experiment with low, medium, and high N treatments (LN, MN, and HN). The dynamic changes in SPAD value from heading to maturity were measured and fitted with quadratic function to extract leaf color-changing parameters; labeled 15N was used as N source after heading to trace the source of N in the panicle and the remobilization of vegetative organ N. The results showed that 67.37–72.38% of the panicle N was transported from vegetative organs, the N transport efficiency was the upper three leaves > lower leaves > stem, and about 3.1–35.0% of the transported N was lost via volatilization. The effects of exogenous N concentration on N harvest index, N dry matter/grain production efficiency, N reuse efficiency, and N loss were closely related to leaf color-changing parameters. In MN and HN treatment, the N loss was negatively correlated with the onset time of leaf color-changing (T0) and the final leaf color index (CIf), but positively correlated with the leaf color-changing rate (Rmean). Increasing the supply of exogenous N increased T0 and CIf, but decreased Rmean, N transport/reuse efficiency, N harvest index, and N dry matter/grain production efficiency. Compared to the cultivar CY167 with normal leaf color-changing, the “stay-green” cultivar CY927 had higher T0, CIf, and lower Rmean, resulting in less N volatilization loss, lower N harvest index and N transport efficiency, while higher N reuse efficiency. In conclusion, the exogenous N supply affects leaf color by influencing the transportation and reuse of leaf N during the grain-filling stage.

Background: GLI3 gene mutations can result in various forms of polysyndactyly, such as Greig cephalopolysyndactyly syndrome (GCPS, MIM: #175700), Pallister–Hall syndrome (PHS, MIM: #146510), and isolated polydactyly (IPD, MIM: #174200, #174700). Reports on IPD-associated GLI3 mutations are rare. In this study, a novel GLI3 mutation was identified in a Chinese family with IPD. Results: We report a family with six members affected by IPD. The family members demonstrated several special phenotypes, including sex differences, abnormal finger joint development, and different polydactyly types. We identified a novel frameshift variant in the GLI3 gene (NM_000168.6: c.1820_1821del, NP_000159.3: p.Tyr607Cysfs*9) by whole-exome sequencing. Further analysis suggested that this mutation was the cause of polydactyly in this family. Conclusions: The discovery of this novel frameshift variant in our study further solidifies the relationship between IPD and GLI3 and expands the previously established spectrum of GLI3 mutations and associated phenotypes.

Abstract Background Oxidative stress (OS) is a key pathophysiological mechanism in Crohn’s disease (CD). OS-related genes can be affected by environmental factors, intestinal inflammation, gut microbiota, and epigenetic changes. However, the role of OS as a potential CD etiological factor or triggering factor is unknown, as differentially expressed OS genes in CD can be either a cause or a subsequent change of intestinal inflammation. Herein, we used a multi-omics summary data-based Mendelian randomization (SMR) approach to identify putative causal effects and underlying mechanisms of OS genes in CD. Methods OS-related genes were extracted from the GeneCards database. Intestinal transcriptome datasets were collected from the Gene Expression Omnibus (GEO) database and meta-analyzed to identify differentially expressed genes (DEGs) related to OS in CD. Integration analyses of the largest CD genome-wide association study (GWAS) summaries with expression quantitative trait loci (eQTLs) and DNA methylation QTLs (mQTLs) from the blood were performed using SMR methods to prioritize putative blood OS genes and their regulatory elements associated with CD risk. Up-to-date intestinal eQTLs and fecal microbial QTLs (mbQTLs) were integrated to uncover potential interactions between host OS gene expression and gut microbiota through SMR and colocalization analysis. Two additional Mendelian randomization (MR) methods were used as sensitivity analyses. Putative results were validated in an independent multi-omics cohort from the First Affiliated Hospital of Sun Yat-sen University (FAH-SYS). Results A meta-analysis from six datasets identified 438 OS-related DEGs enriched in intestinal enterocytes in CD from 817 OS-related genes. Five genes from blood tissue were prioritized as candidate CD-causal genes using three-step SMR methods: BAD, SHC1, STAT3, MUC1, and GPX3. Furthermore, SMR analysis also identified five putative intestinal genes, three of which were involved in gene–microbiota interactions through colocalization analysis: MUC1, CD40, and PRKAB1. Validation results showed that 88.79% of DEGs were replicated in the FAH-SYS cohort. Associations between pairs of MUC1–Bacillus aciditolerans and PRKAB1–Escherichia coli in the FAH-SYS cohort were consistent with eQTL–mbQTL colocalization. Conclusions This multi-omics integration study highlighted that OS genes causal to CD are regulated by DNA methylation and host-microbiota interactions. This provides evidence for future targeted functional research aimed at developing suitable therapeutic interventions and disease prevention.

This study attempts to interpret the urban form of the Japanese cities through the natural spatial reference of front and back which is deeply rooted in Japanese culture. The aim is to provide workable guidance for interpreting the urban form, and for creating diverse and active commercial spaces in Japan and beyond. Based on the physical built environment, this study proposes a parameter of interface which is defined by components taken from both surface of the building and the objects around. The interface is categorized into four types by the combination of main-component of front (F)/back (B) and sub-component of front (f)/back (b), namely Ff, Fb, Bf, and Bb. The approach is demonstrated in the typical commercial district of Shibuya, Tokyo. By analyzing the distributional features of the interface quantitatively, the scopes and attributes of front and back-side space are figured out. According to the distributional similarity of the interface, we sort the urban space into front-side space defined by Ff and back-side space defined by Fb, Bf, and Bb. Thereinto, the ambiguous back-side space defined by Fb and Bf supports diverse possibilities and highly involves in the everyday life of Japanese people.

It has been shown that dexmedetomidine (Dex) could attenuate postoperative cognitive dysfunction (POCD) via targeting circular RNAs (circRNAs). Circ-Shank3 has been found to be involved in the neuroprotective effects of Dex against POCD. However, the role of circ-Shank3 in POCD remains largely unknown. Reverse transcription quantitative PCR (RT-qPCR) was performed to detect circ-Shank3 and miR-140-3p levels in lipopolysaccharide (LPS)-treated microglia BV-2 cells in the absence or presence of Dex. The relationship among circ-Shank3, miR-140-3p and TLR4 was confirmed by dual-luciferase reporter assay. Additionally, Western blot and immunofluorescence (IF) assays were conducted to evaluate TLR4, p65 and Iba-1 or CD11b levels in cells. In this study, we found that Dex notably decreased circ-Shank3 and TLR4 levels and elevated miR-140-3p level in LPS-treated BV2 cells. Mechanistically, circ-Shank3 harbor miR-140-3p, functioning as a miRNA sponge, and then miR-140-3p targeted the 3’-UTR of TLR4. Additionally, Dex treatment significantly reduced TLR4 level and phosphorylation of p65, and decreased the expressions of microglia markers Iba-1 and CD11b in LPS-treated BV2 cells. As expected, silenced circ-Shank3 further reduced TLR4, p65 and Iba-1 and CD11b levels in LPS-treated BV2 cells in the presence of Dex, whereas these phenomena were reversed by miR-140-3p inhibitor. Collectively, our results found that Dex could attenuate the neuroinflammation and microglia activation in BV2 cells exposed to LPS via targeting circ-Shank3/miR-140-3p/TLR4 axis. Our results might shed a new light on the mechanism of Dex for the treatment of POCD.

Ca, Mg, as the main components in water, are not only essential nutrients for life but are also an important index of water hardness. Rapid detection of the element content is of great significance for water quality evaluation and nutrient balance in planting and breeding water. Traditional laboratory analysis methods are time consuming and involve complex procedures. Ion cross sensitivity and response drift also limit the application of online sensors. These disadvantages are not in line with the precise control and rapid response required for practical applications. Here, we propose a rapid automatic Ca, Mg ion concentration detection method using Laser-induced breakdown spectroscopy. Based on a cation exchange membrane, an automatic control system integrating water sampling, hybrid reacting, attachment drying and spectra measuring was constructed. The testing time for one sample could be compressed to 5 min. Consequently, it met the requirements of accuracy and timeliness of water element regulation. The proposed system can provide new technical means for large-scale aquaculture, soilless cultivation of facilities and other scenarios aiming at accurate measurement and control of elements in water body.

Abstract Before the practical application of rechargeable Zn–air batteries (ZABs), a critical issue regarding the inherent slow reaction kinetics of the oxygen reduction (ORR) and oxygen evolution (OER) must be addressed. Here, we fabricate a cost‐effective bifunctional oxygen electrocatalyst with a self‐antistacking structure, where three‐dimensional (3D) Fe–Co bimetallic oxide particles (FeCoOx) are directly grown on 2D N‐doped graphene (NG). The in situ grown FeCoOx particles can alleviate the NG interlaminar restacking, ensuring abundant channels for diffusion of O2/OH− species, while the NG allows rapid electron flow. Benefiting from this self‐antistacking 3D‐on‐2D structure and synergetic electrocatalysis, FeCoOx@NG demonstrated excellent activity for both ORR and OER (ΔE = 0.78 V), which is superior to that of the binary mixtures of Pt/C and RuO2 (ΔE = 0.83 V). A homemade ZAB with 20%‐FeCoOx@NG delivers a specific capacity of 758.9 mAh g−1, a peak power density of 215 mW cm−2, and long‐term cyclability for over 400 h. These research results suggest that designing a bimetallic oxide/N‐doped carbon 3D‐on‐2D nanoarchitecture using an in situ growth strategy is an attractive and feasible solution to overcome electrocatalytic problems in ZABs.

ABSTRACT The increased carbapenem resistance among Pseudomonas aeruginosa has become a serious health issue worldwide. We reported an extensively drug-resistant (XDR) P. aeruginosa PA30 isolate which belonged to sequence type ST463 and contained an IncP-2 plasmid (pPA30_1) carrying two genes, namely, blaIMP-45 and blaAFM-1, which encoded the metallo-β-lactamases AFM-1 and IMP-45, respectively. Additionally, the strain had a plasmid (pPA30_2) with two copies of the blaKPC-2 genes embedded. The plasmid pPA30_1 was highly similar to the previously reported plasmid pHS17-127, which has the same genetic architecture. This plasmid contained blaIMP-45, located in a second gene cassette of the integron In786, carried by a Tn1403-derivative transposon acquiring an ISCR27n3-blaAFM-1 structure. Interestingly, the transposon in pPA30_1 acquired an extra ISCR1-qnrVC6 module and formed a novel transposon, which was subsequently annotated as Tn6485f. The blaKPC-2 genes in pPA30_2 underwent duplication due to the inversion of the IS26-blaKPC-2-IS26 element, which resulted in two copies of blaKPC-2. IMPORTANCE The ST463 clone is an emerging high-risk sequence type that is spreading with blaKPC-2-containing plasmids. The core blaKPC-2 genetic platform is ISKpn27-blaKPC-2-ISKpn6 in almost all samples, and the adjacent region beyond the core platform varies by IS26-mediated inversion or duplication events, amplifying the blaKPC-2 gene copies. The ST463 P. aeruginosa strain PA30 in our study contains another two metallo-β-lactamase genes, namely, blaIMP-45 and blaAFM-1, in a novel transposon Tn6485f that is harbored by the IncP-2 megaplasmid. The pPA30_1 carrying blaIMP-45 and blaAFM-1 is highly related to pHS17-127 from the ST369 P. aeruginosa strain, indicating the putative dissemination of the megaplasmid between different clones.

Jump and pull-in instability are common nonlinear dynamic behaviors leading to the loss of the performance reliability and structural safety of electrostatic micro gyroscopes. To achieve a better understanding of these initial-sensitive phenomena, the dynamics of a micro gyroscope system considering the nonlinearities of the stiffness and electrostatic forces are explored from a global perspective. Static and dynamic analyses of the system are performed to estimate the threshold of the detecting voltage for static pull-in, and dynamic responses are analyzed in the driving and detecting modes for the case of primary resonance and 1:1 internal resonance. The results show that, when the driving voltage frequency is a bit higher than the natural frequency, a high amplitude of the driving AC voltage may induce the coexistence of bistable periodic responses due to saddle-node bifurcation of the periodic solution. Basins of attraction of bistable attractors provide evidence that disturbance of the initial conditions can trigger a jump between bistable attractors. Moreover, the Melnikov method is applied to discuss the condition for pull-in instability, which can be ascribed to heteroclinic bifurcation. The validity of the prediction is verified using the sequences of safe basins and unsafe zones for dynamic pull-in. It follows that pull-in instability can be caused and aggravated by the increase in the amplitude of the driving AC voltage.

Objective: To evaluate the clinical value of epidermal growth factor receptor (EGFR) detection in pleural effusion cell blocks among patients with non-small-cell lung cancer (NSCLC). Methods: From July 2016 to September 2018, EGFR gene mutations in 40 lung tumor tissue samples and pleural fluid samples from NSCLC patients in Jinhua Municipal Central Hospital were assessed by the amplification refractory mutation system method. The EGFR results of the two types of samples were compared using the paired Chi-square test, and the mutation positive rates in EGFR exons 18, 19, 20 and 21 were compared between the two types of specimens using the four-grid Chi-square test. Results: Among the 40 tissue samples and pleural effusion samples, 21 and 18 cases of EGFR mutations were detected, respectively, and the mutation positive rates were 52.5% and 45%, respectively. The κ value of the consistency test of the two specimens was 0.851. There were no significant differences in the mutation positive rates in EGFR exons 18, 19, 20, and 21 between the two types of specimens. Conclusion: The EGFR results of pleural fluid and tissue samples were in good agreement. Therefore, we can use pleural fluid samples to detect EGFR mutations to guide tyrosine kinase inhibitor treatment for NSCLC patients in whom tumor tissue samples cannot be obtained.

Background The purpose of this study was to investigate the risk factors of postoperative complications and reliable prognostic factors of long‐term survival in HIV‐infected patients with non‐small cell lung cancer (NSCLC). Methods HIV‐infected patients with NSCLC who underwent surgical treatment were retrospectively studied; a single‐institutional analysis was conducted from November 2011 to August 2018. Pre‐ and postoperative clinical data, including age, gender, smoking history, highly active antiretroviral therapy (HAART), CD4+ T cell count, HIV viral load, cancer histology, clinical and pathological stage (p‐stage), surgical result, Glasgow Prognostic Score (GPS), the Charlson comorbidity index (CCI), survival time and postoperative complications were collected. Results A total of 33 HIV‐infected patients with NSCLC were enrolled of which 18 (54.7%) had preoperative comorbidities and postoperative complications were observed in 22 (66.7%) patients. Thirty‐day mortality was not observed in these patients. Median survival time after surgery was 65 months: the MST of p‐stage I patients was 65 months; p‐stage II MST was unestimable; p‐stage III MST was 21 months. Univariate analyses showed that postoperative complications were associated with HIV viral load (P = 0.002), CCI (P = 0.027), HAART (P = 0.028) and CD4+ T cell count (P = 0.045). However, multiple logistic regression analysis showed no correlation between HAART and postoperative complications. The p‐stage was an independent prognostic factor for survival time. Conclusions In our single‐arm retrospective analysis, the risk factors for postoperative complications in HIV‐infected patients with NSCLC were HIV viral load, CCI and CD4+ T cell counts. The p‐stage was a predictive factor for long‐term survival.

Abstract Background Abnormal laryngeal structures are likely to be associated with a difficult laryngoscopy procedure. Currently, laryngeal structures can be measured by ultrasonography, however, little research has been performed on the potential role of ultrasound on the evaluation of a difficult laryngoscopy. The present study investigated the value of laryngeal structure measurements for predicting a difficult laryngoscopy. Objective The main objective of this study was to explore the value of laryngeal structure measurements for predicting a difficult laryngoscopy. Methods Two hundred and eleven adult patients (over 18 years old) were recruited to undergo elective surgery under general anesthesia via endotracheal intubation. Ultrasound was utilized to measure the distance between the skin and thyroid cartilage (DST), the distance between the thyroid cartilage and epiglottis (DTE), and the distance between the skin and epiglottis (DSE) in the parasagittal plane. These metrics were then investigated as predictors for classifying a laryngoscopy as difficult vs easy, as defined by the Cormack and Lehane grading scale. Results Multivariate logistic regression showed that the DSE, but not DST or DTE, was significantly related to difficult laryngoscopies. Specifically, a DSE ≥ 2.36 cm predicted difficult laryngoscopies with a sensitivity and specificity of 0.818 (95% CI: 0.766–0.870) and 0.856 (95% CI: 0.809–0.904). Furthermore, when combining the best model constructed of other indicators (i.e. sex, body mass index, modified Mallampati test) to predict the difficult laryngoscopy, the AUC reached 93.28%. Conclusion DSE is an independent predictor of a difficult laryngoscopy; a DSE cutoff value of 2.36 cm is a better predictor of a difficult laryngoscope than other ultrasound or physiological measurements for predicting a difficult laryngoscope. Nevertheless, it’s more valuable to apply the best model of this study, composed of various physiological measurements, for this prediction purpose.

In this study, the damage characteristics of the slit charge pack along the rock slitting and the vertical slitting directions were investigated using green sandstone as the subject. Split-Hopkinson pressure bar (SHPB) experiments were performed on green sandstone, and the dynamic mechanical properties of rock specimen were analyzed in the slitting and vertical slitting directions. Based on the SHPB experiments of the rock specimens in different damage zones along the rock slitting and the vertical slitting directions combined with the fractal theory, the distribution pattern of rock fracture fragmentation was investigated at different positions in the kerf direction and vertical kerf direction. The results of this study show that the dynamic strength of the rock corresponds to the damage degree of the rock, which is greater in the direction of the slit than that in the perpendicular direction of the slit. In addition, the core at 150 mm distance from the blast hole perpendicular to the slit direction could easily bear the blast loads. The lumpiness distribution of rock specimens under impact load shows good statistical self-similarity. The evolution law of fractal dimension shows that with increasing distance from the core to the blast hole, the fractal dimension of the specimen after failure increases. The fractal dimension of the specimen perpendicular to the slit direction is greater than that of the specimen along the slit direction at the same distance.

The investigation of global bifurcation behaviors the vibrating structures of micro-electromechanical systems (MEMS) has received substantial attention. This paper considers the vibrating system of a typical bilateral MEMS resonator containing fractional functions and multiple potential wells. By introducing new variations, the Melnikov method is applied to derive the critical conditions for global bifurcations. By engaging in the fractal erosion of safe basin to depict the phenomenon pull-in instability intuitively, the point-mapping approach is used to present numerical simulations which are in close agreement with the analytical prediction, showing the validity of the analysis. It is found that chaos and pull-in instability, two initial-sensitive phenomena of MEMS resonators, can be due to homoclinic bifurcation and heteroclinic bifurcation, respectively. On this basis, two types of delayed feedback are proposed to control the complex dynamics successively. Their control mechanisms and effect are then studied. It follows that under a positive gain coefficient, delayed position feedback and delayed velocity feedback can both reduce pull-in instability; nevertheless, to suppress chaos, only the former can be effective. The results may have some potential value in broadening the application fields of global bifurcation theory and improving the performance reliability of capacitive MEMS devices.

Global dynamics of a piezoelectric energy harvester with tristable potential is investigated. The dynamical model of a cantilever beam energy harvester is considered; its static bifurcation is also discussed. Multiple intra-well attractors and their basins of attraction are presented to discuss the mechanism of multistability and its initial sensitivity. Moreover, the Melnikov method is applied to present the conditions for global bifurcations and the induced complex dynamics. The results show that the variation of coefficients of the polynomial may affect the number and shapes of potential wells, while the increase of the excitation amplitude may trigger multistability around one equilibrium, initial-sensitive jump, inter-well attractor and chaos. The results may provide some theoretical reference for increasing the working performance of energy harvesters.

Multiple attractors and their fractal basins of attraction can lead to the loss of global stability and integrity of Micro Electro Mechanical Systems (MEMS). In this paper, multistability of a class of electrostatic bilateral capacitive micro-resonator is researched in detail. First, the dynamical model is established and made dimensionless. Second, via the perturbating method and the numerical description of basins of attraction, the multiple periodic motions under primary resonance are discussed. It is found that the variation of AC voltage can induce safe jump of the micro resonator. In addition, with the increase of the amplitude of AC voltage, hidden attractors and chaos appear. The results may have some potential value in the design of MEMS devices.

A novel and practical asymmetric synthesis of dapoxetine hydrochloride by using the chiral auxiliary (S)-tert-butanesulfinamide was explored. The synthesis was concise, mild, and easy to perform. The overall yield and stereoselectivity were excellent.

Massively parallel sequencing (MPS) combined with bioinformatic analysis has been widely applied to detect fetal chromosomal aneuploidies such as trisomy 21, 18, 13 and sex chromosome aneuploidies (SCAs) by sequencing cell-free fetal DNA (cffDNA) from maternal plasma, so-called non-invasive prenatal testing (NIPT). However, many technical challenges, such as dependency on correct fetal sex prediction, large variations of chromosome Y measurement and high sensitivity to random reads mapping, may result in higher false negative rate (FNR) and false positive rate (FPR) in fetal sex prediction as well as in SCAs detection. Here, we developed an optimized method to improve the accuracy of the current method by filtering out randomly mapped reads in six specific regions of the Y chromosome. The method reduces the FNR and FPR of fetal sex prediction from nearly 1% to 0.01% and 0.06%, respectively and works robustly under conditions of low fetal DNA concentration (1%) in testing and simulation of 92 samples. The optimized method was further confirmed by large scale testing (1590 samples), suggesting that it is reliable and robust enough for clinical testing.

Context • Peripherally inserted central catheters (PICCs) have a high incidence of catheter occlusion, but research exploring the risk factors for such an occlusion for patients in intensive care units (ICUs) is lacking. Objective • The study intended to examine the impact of multiple risk factors on the occurrence of PICC catheter occlusion to find evidence that can help clinical medical staff identify patients at an early stage who are at high risk of a catheter occlusion. Design • The research team performed a retrospective, observational clinical study. Setting • The study took place at a tertiary general hospital, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University in Wenzhou, China. Participants • Participants were 300 patients with a PICC who received treatment in the hospital’s adult ICU between January 2019 and April 2022. Groups • According to the time of catheterization, the research team numbered the 1~300 participants and then selected one starting number to divided them into two groups according to the random number table. These two groups were: (1) a training group with 225 participants and (2) validation group with 75 participants. Outcome Measures • The main outcome measure was the evaluation of the factors impacting patients who had had a PICC occlusion during catheter retention, including complete and incomplete occlusions, to build a risk prediction model of PICC occlusion. A secondary outcome measure was the occurrence of extubation of the PICC discharge of the ICU patient. The research team performed a univariate analysis of the training group’s data and a multivariate logistic regression analysis of the risk factors. The team: (1) built a risk prediction model of PICC occlusion using the independent risk factors for catheter occlusion for PICC patients in an ICU and (2) used the Hosmer-Lemeshow goodnessof-fit test to test the prediction model. A two tailed using p>0.05 indicated that the model had a good fit. Then, the team applied the model to the validation group and evaluated the model’s predictive ability using a receiver operating characteristic (ROC) curve. The team considered an area under the curve (AUC) >0.5 to have predictive value. The larger the area was, the better the predicted value was. The incidence of PICC occlusion in the training group was 18.22%, including 10 participants with complete occlusion and 31 with partial occlusion. The team used the SPSS 22.0 and R software for statistical analysis. Results • The univariate analysis showed that 13 factors were associated with PICC occlusion, including: (1) an age ≥65 years (P<.001), a BMI of ≥24 kg/m2 (P<.001), (2) a BMI of ≥24kg/m² (P = .002), (3) diabetes (P < .001), (4) stroke (P < .001), (5) hypertension (P < .001), (6) malignant tumors (P < .001), (7) a history of deep vein thrombosis (P < .001), (8) limb activity (P < .001), (10) flushing and sealing pipe frequency of Q8h (P=.035), (11) retention time (P<.001), (12) an increased platelet count (P = .036), (13) blood transfusions (P < .001), and (14) intravenous nutrition (P<.001). The independent risk factors for PICC occlusion included: (1) age ≥65 years—OR=1.224, P=.028; (2) BMI ≥24 kg/m² —OR=1.679, P=.004; (3) diabetes—OR=1.343, P = .017; (4) malignant tumors—OR=2.736, P < .001; (5) blood transfusions—OR=1.947, P<.001), and (6) intravenous nutrition— OR=2.021, P<.001. The frequency of flushing and sealing the pipe (Q8h)—OR=-2.145, P = .002—was a protective factor. In the training group, the area under the curve (AUC) for predicting a PICC occlusion was 0.917. The Hosmer-Lemeshow test of the prediction model showed that no significant differences existed in the test results within the model (χ² =5.830, P=.666), indicating that the model passed the internal validation. The ideal and calibration curves of the prediction model were highly coincident, and the model was well calibrated. The Hosmer-Lemeshow test of the validation group showed that no significant differences existed in the test results outside the model, suggesting that the model had high consistency. Conclusions • Age ≥65 years, BMI ≥24 kg/m2, diabetes, malignant tumors, blood transfusions, and intravenous nutrition were independent risk factors for PICC occlusion, while the frequency of flushing and sealing pipe (Q8h) was a protective factor. This prediction model had an outstanding ability to discriminate in identifying patients with a high-risk of PICC occlusion in the ICU. [ABSTRACT FROM AUTHOR]