Halogenation of Anilines: Formation of Haloacetonitriles and Large-Molecule Disinfection Byproducts.

Aniline-related structures are common in anthropogenic chemicals, such as pharmaceuticals and pesticides. Compared with the widely studied phenolic compounds, anilines have received far less assessment of their disinfection byproduct (DBP) formation potential, even though anilines and phenols likely exhibit similar reactivities on their respective aromatic rings. In this study, a suite of 19 aniline compounds with varying N- and ring-substitutions were evaluated for their formation potentials of haloacetonitriles and trihalomethanes under free chlorination and free bromination conditions. Eight of the aniline compounds formed dichloroacetonitrile at yields above 0.50%; the highest yields were observed for 4-nitroaniline, 3-chloroaniline, and 4-(methylsulfonyl)aniline (1.6-2.3%). Free bromination generally resulted in greater haloacetonitrile yields with the highest yield observed for 2-ethylaniline (6.5%). The trihalomethane yields of anilines correlated with their haloacetonitrile yields. Product analysis of aniline chlorination by liquid chromatography-high-resolution mass spectrometry revealed several large-molecule DBPs, including chloroanilines, (chloro)hydroxyanilines, (chloro)benzoquinone imines, and ring-cleavage products. The product time profiles suggested that the reaction pathways include initial ring chlorination and hydroxylation, followed by the formation of benzoquinone imines that eventually led to ring cleavage. This work revealed the potential of aniline-related moieties in micropollutants as potent precursors to haloacetonitriles and other emerging large-molecule DBPs with the expected toxicity.

Abnormal expression of autophagy proteins in the duodenum of patients with functional dyspepsia: A preliminary study.

BACKGROUND AND STUDY AIMS: Functional dyspepsia (FD) is a common disease with an unclear pathology. Autophagy is associated with inflammation and has been proposed to play a role in the development of FD. This study aimed to evaluate expression of the autophagy proteins beclin1 and p62/SQSTM1 in patients with FD. PATIENTS AND METHODS: Duodenal mucosal tissues were collected from 10 patients with FD and 10 asymptomatic controls. The extent of autophagy was determined by examining expression levels of beclin1 and p62/SQSTM1 using quantitative polymerase chain reaction and immunohistochemistry techniques. RESULTS: Lower expression levels of beclin1 protein were detected in the duodenal bulb (D1) and the second portion of the duodenum (D2) in patients with FD compared with asymptomatic controls. Higher levels of p62 protein were expressed in D1 in patients with FD than in controls. No differences in mRNA expression of beclin1 and p62 were observed between patients with FD and controls. CONCLUSION: Abnormal autophagy was involved in FD, which may be associated with the pathogenesis of FD.

Exploring galectin-3's role in predicting mild cognitive impairment in type 2 diabetes and its regulation by miRNAs.

Objective: This study aimed to investigate the role of galectin-3 (Gal-3; coded by LGALS3 gene), as a biomarker for MCI in T2DM patients and to develop and validate a predictive nomogram integrating galectin-3 with clinical risk factors for MCI prediction. Additionally, microRNA regulation of LGALS3 was explored. Methods: The study employed a cross-sectional design. A total of 329 hospitalized T2DM patients were recruited and randomly allocated into a training cohort (n = 231) and a validation cohort (n = 98) using 7:3 ratio. Demographic data and neuropsychological assessments were recorded for all participants. Plasma levels of galectin-3 were measured using ELISA assay. We employed Spearman's correlation and multivariable linear regression to analyze the relationship between galectin-3 levels and cognitive performance. Furthermore, univariate and multivariate logistic regression analyses were conducted to identify independent risk factors for MCI in T2DM patients. Based on these analyses, a predictive nomogram incorporating galectin-3 and clinical predictors was developed. The model's performance was evaluated in terms of discrimination, calibration, and clinical utility. Regulatory miRNAs were identified using bioinformatics and their interactions with LGALS3 were confirmed through qRT-PCR and luciferase reporter assays. Results: Galectin-3 was identified as an independent risk factor for MCI, with significant correlations to cognitive decline in T2DM patients. The developed nomogram, incorporating Gal-3, age, and education levels, demonstrated excellent predictive performance with an AUC of 0.813 in the training cohort and 0.775 in the validation cohort. The model outperformed the baseline galectin-3 model and showed a higher net benefit in clinical decision-making. Hsa-miR-128-3p was significantly downregulated in MCI patients, correlating with increased Gal-3 levels, while Luciferase assays confirmed miR-128-3p's specific binding and influence on LGALS3. Conclusion: Our findings emphasize the utility of Gal-3 as a viable biomarker for early detection of MCI in T2DM patients. The validated nomogram offers a practical tool for clinical decision-making, facilitating early interventions to potentially delay the progression of cognitive impairment. Additionally, further research on miRNA128's regulation of Gal-3 levels is essential to substantiate our results.

Multi-dimensional optical information acquisition based on a misaligned unipolar barrier photodetector.

Acquiring multi-dimensional optical information, such as intensity, spectrum, polarization, and phase, can significantly enhance the performance of photodetectors. Incorporating these dimensions allows for improved image contrast, enhanced recognition capabilities, reduced interference, and better adaptation to complex environments. However, the challenge lies in obtaining these dimensions on a single photodetector. Here we propose a misaligned unipolar barrier photodetector based on van der Waals heterojunction to address this issue. This structure enables spectral detection by switching between two absorbing layers with different cut-off wavelengths for dual-band detection. For polarization detection, anisotropic semiconductors like black phosphorus and black arsenic phosphorus inherently possess polarization-detection capabilities without additional complex elements. By manipulating the crystal direction of these materials during heterojunction fabrication, the device becomes sensitive to incident light at different polarization angles. This research showcases the potential of the misaligned unipolar barrier photodetector in capturing multi-dimensional optical information, paving the way for next-generation photodetectors.

LinearAlifold: Linear-time consensus structure prediction for RNA alignments.

Predicting the consensus structure of a set of aligned RNA homologs is a convenient method to find conserved structures in an RNA genome, which has many applications including viral diagnostics and therapeutics. However, the most commonly used tool for this task, RNAalifold, is prohibitively slow for long sequences, due to a cubic scaling with the sequence length, taking over a day on 400 SARS-CoV-2 and SARS-related genomes (∼30,000nt). We present LinearAlifold, a much faster alternative that scales linearly with both the sequence length and the number of sequences, based on our work LinearFold that folds a single RNA in linear time. Our work is orders of magnitude faster than RNAalifold (0.7 h on the above 400 genomes, or ∼36× speedup) and achieves higher accuracies when compared to a database of known structures. More interestingly, LinearAlifold's prediction on SARS-CoV-2 correlates well with experimentally determined structures, substantially outperforming RNAalifold. Finally, LinearAlifold supports two energy models (Vienna and BL*) and four modes: minimum free energy (MFE), maximum expected accuracy (MEA), ThreshKnot, and stochastic sampling, each of which takes under an hour for hundreds of SARS-CoV variants. Our resource is at: https://github.com/LinearFold/LinearAlifold (code) and http://linearfold.org/linear-alifold (server).

Disturbed carnitine metabolism is independently correlated with sarcopenia and prognosis in patients on hemodialysis.

BACKGROUND & AIMS: Sarcopenia is frequent in hemodialysis patients and associated with an increased likelihood of adverse outcomes. Early identification of the risk of sarcopenia and effective intervention are of great importance for dialysis patients. However, little research has been carried out on potential biomarkers of sarcopenia in hemodialysis patients. The aim of this study was to investigate whether serum carnitine or acylcarnitine levels are biomarkers of sarcopenia in hemodialysis patients, and whether these are prognostic factors for occurrence of complications. METHODS: This prospective clinical pilot study enrolled patients (n = 259) who were treated in the Blood Purification Center from May 2021 to July 2022, all participants were followed-up for 1- year. Serum carnintine and acylcarnitine (AC) were measured using our previously reported targeted liquid chromatography tandem mass spectrometry (LC-MS/MS) method. The correlations between carnitine or acylcarnitine levels with sarcopenia and prognosis in patients were analysed. RESULTS: The C0 (Free carnitine, FC) and total carnitine (TC) levels were significantly lower in the sarcopenia group than in the nonsarcopenia group [nonsarcopenia vs. sarcopenia: 20.97 (16.96, 25.83) vs. 17.77 (14.30, 22.78); p = 0.002] and [nonsarcopenia vs. sarcopenia: 30.12 (24.76, 36.62) vs. 26.03 (21.30, 32.01); p = 0.003]. Besides, significant difference between the groups were noted in low free carnitine (C0 < 20 µmol/L) patients (nonsarcopenia vs. sarcopenia: 72 (42.4%) vs. 56 (62.9%); p = 0.002) and high C2/C0 ratio (>0.4) patients (nonsarcopenia vs. sarcopenia: 36 (21.2%) vs. 30 (33.7%); p = 0.028). By multivariable analysis, the disturbed CM defined as C0 deficient and/or C2/C0 carnitine ratio abnormal rise was independently and significantly correlated with the prevalence of sarcopenia after adjusting for some confounding factors, such as age, gender and dialysis duration (P values for trend <0.05). Hemodialysis patients with sarcopenia [OR: 3.214 (1.307,7.904)] and disturbed CM [OR: 3.217 (1.112,9.305)] both had a 3-fold increased risk of falling and fracture after one year follow up. In addition, age and sarcopenia [OR: 2.883 (1.321, 6.289)] were independently and positively associated with incidence of Cardio- and cerebro-vascular events. CONCLUSION: Disturbed carnitine metabolism is independently correlated with sarcopenia and prognosis in patients with hemodialysis. Serum carnitine level and C0/C2 ratio has the potential to be a simple, objective, and quick test for sarcopenia assessment whether such an intervention should be carried out for dialysis patients.

Lightweight bobbin yarn detection model for auto-coner with yarn bank.

The automated replacement of empty tubes in the yarn bank is a critical step in the process of automatic winding machines with yarn banks, as the real-time detection of depleted yarn on spools and accurate positioning of empty tubes directly impact the production efficiency of winding machines. Addressing the shortcomings of traditional methods, such as poor adaptability and low sensitivity in optical and visual tube detection, and aiming to reduce the computational and detection time costs introduced by neural networks, this paper proposes a lightweight yarn spool detection model based on YOLOv8. The model utilizes Darknet-53 as the backbone network, and due to the dense spatial distribution of yarn spool targets, it incorporates large selective kernel units to enhance the recognition and positioning of dense targets. To address the issue of excessive focus on local features by convolutional neural networks, a bi-level routing attention mechanism is introduced to capture long-distance dependencies dynamically. Furthermore, to balance accuracy and detection speed, a FasterNeck is constructed as the neck network, replacing the original convolutional blocks with Ghost convolutions and integrating with FasterNet. This design minimizes the sacrifice of detection accuracy while achieving a significant improvement in inference speed. Lastly, the model employs weighted IoU with a dynamic focusing mechanism as the bounding box loss function. Experimental results on a custom yarn spool dataset demonstrate a notable improvement over the baseline model, with a high-confidence mAP of 94.2% and a compact weight size of only 4.9 MB. The detection speed reaches 223FPS, meeting the requirements for industrial deployment and real-time detection.

Research on high-speed classification and location algorithm for logistics parcels based on a monocular camera.

The rapid development of the logistics industry has driven innovations in parcel sorting technology, among which the swift and precise positioning and classification of parcels have become key to enhancing the performance of logistics systems. This study aims to address the limitations of traditional light curtain positioning methods in logistics sorting workshops amidst high-speed upgrades. This paper proposes a high-speed classification and location algorithm for logistics parcels utilizing a monocular camera. The algorithm combines traditional visual processing methods with an enhanced version of the lightweight YOLOv5 object detection algorithm, achieving high-speed, high-precision parcel positioning. Through the adjustment of the network structure and the incorporation of new feature extraction modules and ECIOU loss functions, the model's robustness and detection accuracy have been significantly improved. Experimental results demonstrate that this model exhibits outstanding performance on a customized logistics parcel dataset, notably enhancing the model's parameter efficiency and computational speed, thereby offering an effective solution for industrial applications in high-speed logistics supply.

How to treat major depressive disorder with shorter-duration hypomanic episodes? A case report.

Here we report on a case of a 61-year-old female patient with 7-year history of major depressive disorder with shorter-duration hypomanic episodes who was prescribed with antidepressants which turned out to be ineffective. After a COVID-19 infection, the patient's clinical presentation became sufficient for the diagnosis of bipolar disorder and she was consistently effective on a mood stabilizer and an atypical antipsychotic. The course of treatment in this case suggests bipolar disorder is not a binary disorder, but a continuous spectrum disorder. For patients suffering from major depressive disorder with shorter-duration hypomanic episodes, mood stabilizers and atypical antipsychotics are possibly more suitable than antidepressants.

Rapid in-situ calibration of computational micro-spectrometer with few-shot meta-learning.

Computational micro-spectrometers comprised of detector arrays and encoding structure arrays, such as on-chip Fabry-Perot (FP) cavity filters, have great potential in many in-situ applications owing to their compact size and snapshot imaging ability. Given manufacturing deviation and environmental influence are inevitable, easy and effective calibration for spectrometer is necessary, especially for in-situ applications. Currently calibration strategies based on iterative algorithms or neural networks require accurate measurements of pixel-level (spectral) encoding functions through monochromator or large amounts of standard samples. These procedures are time-consuming and expensive, thereby impeding in-situ applications. Meta-learning algorithms with few-shot learning ability can address this challenge by incorporating the prior knowledge in the simulated dataset. In this work, we propose a meta-learning algorithm free of measuring encoding function or large amounts of standard samples to calibrate a micro-spectrometer with manufacturing deviation effectively. Our micro-spectrometer comprises 16 types of FP filters covering a wavelength range of 550-720 nm. The center wavelength of each filter type deviates from the design up to 6 nm. After calibration with 15 different color data, the average reconstruction error on the test dataset decreased from 7.2 × 10-3 to 1.2 × 10-3, and further decreased to 9.4 × 10-4 when the calibration data increased to 24. The performance is comparable to algorithms trained with measured encoding function both in reconstruction error and generalization ability. We estimated that the cost of in-situ calibration through reflectance measurements of color chart decreased to one percent of the cost through monochromator measurements. By exploiting prior deviation information in simulation data with meta-learning, the efficiency and cost of calibration are significantly improved, thereby facilitating the large-scale production and in-situ application of micro-spectrometers.

Natural History and Outcomes of Individuals With Functional Bowel Disorder: A 9-year Population-Based Longitudinal Study.

INTRODUCTION: Long-term studies characterizing the natural history of functional bowel disorder (FBD) from community-based settings and exploring association with psychological factors are sparse. We aimed to evaluate the evolution of symptoms, health outcomes, and association of FBD with psychological disorders in Chinese population. METHODS: Individuals identified from random sampling of residents of Hangzhou, China, participated in a baseline survey in January 2010. Follow-up phone survey was conducted in December 2018. FBD was diagnosed based on Rome III criteria. RESULTS: Among 452 individuals (mean age 44.6 ± 15.3 years, 174 [38%] male) who completed the study, the prevalence of FBD was 36.3% (95% confidence interval [CI] 32.6-40.0%) at enrollment and 36.1% (95% CI 32.3-39.8%) at follow-up survey ( P = 0.94). However, 214 individuals (47%) had interval change in diagnosis. Although no difference in incidence of organic disease or death was observed, a higher proportion of patients with FBD (16/164, 9.8% vs 9/288, 3.1%; P = 0.003) compared with those without FBD received non-cancer-related abdominal and/or pelvic surgery during follow-up. FBD was associated with anxiety and/or depression at initial (adjusted odds ratio [AOR] = 1.7, 95% CI 1.7-2.7, P = 0.02) and follow-up (AOR = 8.0, 95% CI 3.2-20.0, P < 0.001) surveys. Diagnosis of FBD at baseline was associated with new-onset anxiety and/or depression at follow-up (AOR = 3.2, 95% CI 1.2-8.3, P = 0.01). DISCUSSION: Although the prevalence of FBD remained stable, transformation of symptoms was common over time. Patients with FBD may have increased risk of receiving non-cancer-related abdominal and/or pelvic surgery. FBD symptoms at baseline increased the risk of new-onset anxiety and/or depression by 3.2-fold over the next 9 years.

Interplay between myotubularins and Ca2+ homeostasis.

The myotubularin family, encompassing myotubularin 1 (MTM1) and 14 myotubularin-related proteins (MTMRs), represents a conserved group of phosphatases featuring a protein tyrosine phosphatase domain. Nine members are characterized by an active phosphatase domain C(X)5R, dephosphorylating the D3 position of PtdIns(3)P and PtdIns(3,5)P2. Mutations in myotubularin genes result in human myopathies, and several neuropathies including X-linked myotubular myopathy and Charcot-Marie-Tooth type 4B. MTM1, MTMR6 and MTMR14 also contribute to Ca2+ signaling and Ca2+ homeostasis that play a key role in many MTM-dependent myopathies and neuropathies. Here we explore the evolving roles of MTM1/MTMRs, unveiling their influence on critical aspects of Ca2+ signaling pathways.

Humidity-tolerant and highly sensitive gas sensor for hydrogen sulfide based on WO3 nanocubes modified with CeO2.

The influence of ambient humidity on the gas-sensing characteristics of metal oxide semiconductors has been one of the greatest obstacles for gas-sensing applications. In this paper, the pure WO3 and CeO2-modified WO3 nanocubes were prepared by a simple hydrothermal method, and their gas-sensing characteristics in dry and humid atmospheres were investigated. The results show that CeO2/WO3 demonstrated excellent gas-sensing properties toward H2S with high sensitivity and high selectivity at 115 °C. Noteworthy, the humidity independence of the CeO2/WO3 increased compared to the WO3. The response retentions over the whole humidity range of the CeO2/WO3-6 and CeO2/WO3-15 sensors were 70.3, and 76%, respectively, which were much higher than the WO3 sensor (17.9%). The gas-sensing mechanism of CeO2-modified WO3 is discussed based on the gas sensitivity properties. The obtained results provide a promising route to enhance the anti-humidity properties of metal oxide semiconductor gas sensors.

Self-assembling peptide hydrogel scaffold integrating stem cell-derived exosomes for infected bone defects.

Infected bone defect (IBD) is a great challenge in orthopedics, which involves in bone loss and infection. Here, a self-assembling hydrogel scaffold (named AMP-RAD/EXO), integrating antimicrobial peptides(AMPs), RADA16 and BMSCs exosomes with an innovative strategy, is developed and applied in IBD treatment for sustained antimicrobial ability, accelerating osteoblasts proliferation and promoting bone regeneration. AMPs present an excellent ability to inhibit infection, RADA16 is a self-assembling peptide hydrogel for AMPs delivery, and BMSCs exosomes can promote the bone regeneration. The prepared AMP-RAD/EXO exhibited a polyporous 3D structure for imbibition of BMSCs exosomes and migration of osteoblasts. In vitro studies indicate AMP-RAD/EXO can inhibit the growth of Staphylococcus aureus, accelerate the proliferation and migration of BMSCs. More importantly, in vivo results also prove that AMP-RAD/EXO exhibit an excellent effect on IBD treatment. Thus, the prepared AMP-RAD/EXO provides a multifunctional scaffold concept for bone tissue engineering technology.

Vonoprazan 10 mg or 20 mg vs. lansoprazole 15 mg as maintenance therapy in Asian patients with healed erosive esophagitis: A randomized controlled trial.

BACKGROUND: Erosive esophagitis (EE) is a gastroesophageal reflux disease characterized by mucosal breaks in the esophagus. Proton pump inhibitors are widely used as maintenance therapy for EE, but many patients still relapse. In this trial, we evaluated the noninferiority of vonoprazan vs. lansoprazole as maintenance therapy in patients with healed EE. METHODS: We performed a double-blind, double-dummy, multicenter, phase 3 clinical trial among non-Japanese Asian adults with endoscopically confirmed healed EE from April 2015 to February 2019. Patients from China, South Korea, and Malaysia were randomized to vonoprazan 10 mg or 20 mg once daily or lansoprazole 15 mg once daily for 24 weeks. The primary endpoint was endoscopically confirmed EE recurrence rate over 24 weeks with a noninferiority margin of 10% using a two-sided 95% confidence interval (CI). Treatment-emergent adverse events (TEAEs) were recorded. RESULTS: Among 703 patients, EE recurrence was observed in 24/181 (13.3%) and 21/171 (12.3%) patients receiving vonoprazan 10 mg or 20 mg, respectively, and 47/184 (25.5%) patients receiving lansoprazole (differences: -12.3% [95% CI, -20.3% to -4.3%] and -13.3% [95% CI, -21.3% to -5.3%], respectively), meeting the primary endpoint of noninferiority to lansoprazole in preventing EE recurrence at 24 weeks. Evidence of superiority (upper bound of 95% CI <0%) was also observed. At 12 weeks, endoscopically confirmed EE recurrence was observed in 5/18, 2/20, and 7/20 of patients receiving vonoprazan 10 mg, vonoprazan 20 mg, and lansoprazole, respectively. TEAEs were experienced by 66.8% (157/235), 69.0% (156/226), and 65.3% (158/242) of patients receiving vonoprazan 10 mg, vonoprazan 20 mg, and lansoprazole, respectively. The most common TEAE was upper respiratory tract infection in 12.8% (30/235) and 12.8% (29/226) patients in vonoprazan 10 mg and 20 mg groups, respectively and 8.7% (21/242) patients in lansoprazole group. CONCLUSION: Vonoprazan maintenance therapy was well-tolerated and noninferior to lansoprazole for preventing EE recurrence in Asian patients with healed EE. TRIAL REGISTRATION: https://clinicaltrials.gov; NCT02388737.

A high-performance room-temperature NH3 gas sensor based on WO3/TiO2 nanocrystals decorated with Pt NPs.

In this work, a high-performance room-temperature ammonia (NH3) gas sensor based on Pt-modified WO3-TiO2 nanocrystals was synthesized via a two-step hydrothermal method. The structural properties were characterized by scanning electron microscopy, transmission electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. The 10 at% Pt@WO3-TiO2 nanocrystals present the highest NH3 sensing performance at room temperature. Compared with the nanocrystals without Pt modification, the sensitivity of the Pt@WO3-TiO2 sensor is tenfold higher, with the lowest concentration threshold reaching the 75 ppb level. The response is approximately 92.28 to 50 ppm, and response and recovery times are 23 s and 8 s, respectively. The improved sensing was attributed to a synergetic mechanism involving the space charge layer effect and Pt metal sensitization, enhancing the electron transfer efficiency, oxygen vacancy and specific surface area. This study is expected to guide the development of high-performance room-temperature ammonia sensors for clinical breath testing.

Heterojunctions of Mercury Selenide Quantum Dots and Halide Perovskites with High Lattice Matching and Their Photodetection Properties.

Heterojunction semiconductors have been extensively applied in various optoelectronic devices due to their unique carrier transport characteristics. However, it is still a challenge to construct heterojunctions based on colloidal quantum dots (CQDs) due to stress and lattice mismatch. Herein, HgSe/CsPbBrxI3-x heterojunctions with type I band alignment are acquired that are derived from minor lattice mismatch (~1.5%) via tuning the ratio of Br and I in halide perovskite. Meanwhile, HgSe CQDs with oleylamine ligands can been exchanged with a halide perovskite precursor, acquiring a smooth and compact quantum dot film. The photoconductive detector based on HgSe/CsPbBrxI3-x heterojunction presents a distinct photoelectric response under an incident light of 630 nm. The work provides a promising strategy to construct CQD-based heterojunctions, simultaneously achieving inorganic ligand exchange, which paves the way to obtain high-performance photodetectors based on CQD heterojunction films.

Efficient markerless genetic manipulation of Pasteurella multocida using lacZ and pheSm as selection markers.

Pasteurella multocida is a zoonotic conditional pathogen that infects multiple livestock species, causing substantial economic losses in the animal husbandry industry. An efficient markerless method for gene manipulation may facilitate the investigations of P. multocida gene function and pathogenesis of P. multocida. Herein, a temperature-sensitive shuttle vector was constructed using lacZ as a selection marker, and markerless glgB, opa, and hyaE mutants of P. multocida were subsequently constructed through blue-white colony screening. The screening efficiency of markerless deletion strains was improved by the lacZ system, and the method could be used for multiple gene deletions. However, the fur mutant was unavailable via this method. Therefore, we constructed a pheSm screening system based on mutated phenylalanine tRNA synthetase as a counterselection marker to achieve fur deletion mutant. The transformed strain was sensitive to 20 mM p-chloro-phenylalanine, demonstrating the feasibility of pheSm as a counter-selective marker. The pheSm system was used for markerless deletions of glgB, opa, and hyaE as well as fur that could not be screened by the lacZ system. A comparison of screening efficiencies of the system showed that the pheSm counterselection system was more efficient than the lacZ system and broadly applicable for mutant screening. The methods developed herein may provide valuable tools for genetic manipulation of P. multocida.IMPORTANCEPasteurella multocida is a highly contagious zoonotic pathogen. An understanding of its underlying pathogenic mechanisms is of considerable importance and requires efficient species-specific genetic tools. Herein, we propose a screening system for P. multocida mutants using lacZ or pheSm screening markers. We evaluated the efficiencies of both systems, which were used to achieve markerless deletion of multiple genes. The results of this study support the use of lacZ or pheSm as counterselection markers to improve counterselection efficiency in P. multocida. This study provides an effective genetic tool for investigations of the virulence gene functions and pathogenic mechanisms of P. multocida.

MRI quantitative assessment of the effects of low-carbohydrate therapy on Hashimoto's thyroiditis.

Objective: Hashimoto's thyroiditis is an inflammatory disease, and research suggests that a low-carbohydrate diet may have potential anti-inflammatory effects. This study aims to utilize Dixon-T2-weighted imaging (WI) sequence for a semi-quantitative assessment of the impact of a low-carbohydrate diet on the degree of thyroid inflammation in patients with Hashimoto's thyroiditis. Methods: Forty patients with Hashimoto's thyroiditis were recruited for this study and randomly divided into two groups: one with a normal diet and the other with a low-carbohydrate diet. Antibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) were measured for all participants. Additionally, thyroid water content was semi-quantitatively measured using Dixon-T2WI. The same tests and measurements were repeated for all participants after 6 months. Results: After 6 months of a low-carbohydrate diet, patients with Hashimoto's thyroiditis showed a significant reduction in thyroid water content (94.84 ± 1.57% vs 93.07 ± 2.05%, P < 0.05). Concurrently, a decrease was observed in levels of TPOAb and TgAb (TPOAb: 211.30 (92.63-614.62) vs 89.45 (15.9-215.67); TgAb: 17.05 (1.47-81.64) vs 4.1 (0.51-19.42), P < 0.05). In contrast, there were no significant differences in thyroid water content or TPOAb and TgAb levels for patients with Hashimoto's thyroiditis following a normal diet after 6 months (P < 0.05). Conclusion: Dixon-T2WI can quantitatively assess the degree of thyroid inflammation in patients with Hashimoto's thyroiditis. Following a low-carbohydrate diet intervention, there is a significant reduction in thyroid water content and a decrease in levels of TPOAb and TgAb. These results suggest that a low-carbohydrate diet may help alleviate inflammation in patients with Hashimoto's thyroiditis.

Psychological factors may affect the quality of life in irritable bowel syndrome patients more than the gut itself? A multicenter cross-sectional study.

Background and Aim: Both intestinal symptoms and comorbidities exist in irritable bowel syndrome (IBS) patients and influence their quality of life (QOL). More research is needed to determine how these variables impact the QOL of IBS patients. This study aimed to determine which specific factors had a higher influence on QOL and to further compare the effects of intestinal symptoms and comorbidities on QOL. Methods: IBS patients were recruited from six tertiary hospitals in different regions of China. QOL, gastrointestinal symptoms, and comorbidities were assessed by different scales. Correlation analysis, multiple linear regression, and mediation model were used for statistics. Results: Four hundred fifty-three IBS patients (39.7% women, mean age 45 years) were included and no significant differences in QOL were found across demographic characteristics. Abnormal defecation (r = -0.398), fatigue (r = -0.266), and weakness (r = -0.286) were found to show higher correlation with QOL. More than 40% of IBS patients were found to suffer from varying degrees of anxiety or depression, and anxiety (r = -0.564) and depression (r = -0.411) were significantly negatively correlated with QOL (P < 0.001). Psychological factors showed the strongest impact (ß' = -0.451) and play a strong mediating role in the impact of physiological symptoms on QOL. Anxiety was found to be the strongest factor (ß' = -0.421). Conclusion: Compared with other symptoms, psychological symptoms, particularly anxiety, are more common and have a more negative influence on QOL. The QOL of IBS patients is also significantly impacted by abnormal defecation, abdominal distension, and systemic extraintestinal somatic symptoms. In the treatment of IBS patients with unhealthy mental status, psychotherapy might be prioritized.