The impact of high-altitude migration on cardiac structure and function: a 1-year prospective study.

Introduction: The trend of human migration to terrestrial high altitudes (HA) has been increasing over the years. However, no published prospective studies exist with follow-up periods exceeding 1 month to investigate the cardiac change. This prospective study aimed to investigate the changes in cardiac structure and function in healthy young male lowlanders following long-term migration to HA. Methods: A total of 122 Chinese healthy young males were divided into 2 groups: those migrating to altitudes between 3600 m and 4000 m (low HA group, n = 65) and those migrating to altitudes between 4000 m and 4700 m (high HA group, n = 57). Traditional echocardiographic parameters were measured at sea level, 1 month and 1 year after migration to HA. Results: All 4 cardiac chamber dimensions, areas, and volumes decreased after both 1 month and 1 year of HA exposure. This reduction was more pronounced in the high HA group than in the low HA group. Bi-ventricular diastolic function decreased after 1 month of HA exposure, while systolic function decreased after 1 year. Notably, these functional changes were not significantly influenced by altitude differences. Dilation of the pulmonary artery and a progressive increase in pulmonary artery systolic pressure were observed with both increasing exposure time and altitude. Additionally, a decreased diameter of the inferior vena cava and reduced bicuspid and tricuspid blood flow velocity indicated reduced blood flow following migration to the HA. Discussion: 1 year of migration to HA is associated with decreased blood volume and enhanced hypoxic pulmonary vasoconstriction. These factors contribute to reduced cardiac chamber size and slight declines in bi-ventricular function.

An additional proofreader contributes to DNA replication fidelity in mycobacteria.

The removal of mis-incorporated nucleotides by proofreading activity ensures DNA replication fidelity. Whereas the ε-exonuclease DnaQ is a well-established proofreader in the model organism Escherichia coli, it has been shown that proofreading in a majority of bacteria relies on the polymerase and histidinol phosphatase (PHP) domain of replicative polymerase, despite the presence of a DnaQ homolog that is structurally and functionally distinct from E. coli DnaQ. However, the biological functions of this type of noncanonical DnaQ remain unclear. Here, we provide independent evidence that noncanonical DnaQ functions as an additional proofreader for mycobacteria. Using the mutation accumulation assay in combination with whole-genome sequencing, we showed that depletion of DnaQ in Mycolicibacterium smegmatis leads to an increased mutation rate, resulting in AT-biased mutagenesis and increased insertions/deletions in the homopolymer tract. Our results showed that mycobacterial DnaQ binds to the ß clamp and functions synergistically with the PHP domain proofreader to correct replication errors. Furthermore, the loss of dnaQ results in replication fork dysfunction, leading to attenuated growth and increased mutagenesis on subinhibitory fluoroquinolones potentially due to increased vulnerability to fork collapse. By analyzing the sequence polymorphism of dnaQ in clinical isolates of Mycobacterium tuberculosis (Mtb), we demonstrated that a naturally evolved DnaQ variant prevalent in Mtb lineage 4.3 may enable hypermutability and is associated with drug resistance. These results establish a coproofreading model and suggest a division of labor between DnaQ and PHP domain proofreader. This study also provides real-world evidence that a mutator-driven evolutionary pathway may exist during the adaptation of Mtb.

Overview of Bovine Mastitis: Application of Metabolomics in Screening Its Predictive and Diagnostic Biomarkers.

Bovine mastitis is an inflammatory disease of the mammary glands, and its pathogenesis and diagnosis are complicated. Through qualitative and quantitative analysis of small-molecule metabolites, the metabolomics technique plays an important role in finding biomarkers and studying the metabolic mechanism of bovine mastitis. Therefore, this paper reviews the predictive and diagnostic biomarkers of bovine mastitis that have been identified using metabolomics techniques and that are present in samples such as milk, blood, urine, rumen fluid, feces, and mammary tissue. In addition, the metabolic pathways of mastitis-related biomarkers in milk and blood were analyzed; it was found that the tricarboxylic acid (TCA) cycle was the most significant (FDR = 0.0015767) pathway in milk fluid, and glyoxylate and dicarboxylate metabolism was the most significant (FDR = 0.0081994) pathway in blood. The purpose of this review is to provide useful information for the prediction and early diagnosis of bovine mastitis.

Fabrication of a Microfluidic-Based Device Coated with Polyelectrolyte-Capped Titanium Dioxide to Couple High-Performance Liquid Chromatography with Inductively Coupled Plasma Mass Spectrometry for Mercury Speciation.

Mercury (Hg) is a toxic element which impacts on biological systems and ecosystems. Because the toxicity of Hg species is highly dependent on their concentration levels and chemical forms, the sensitive identification of the chemical forms of Hg-i.e., Hg speciation-is of major significance in providing meaningful information about the sources of Hg exposure. In this study, a microfluidic-based device made of high-clarity poly(methyl methacrylate) (PMMA) was fabricated. Then, titanium dioxide nanoparticles (nano-TiO2s) were attached to the treated channel's interior with the aid of poly(diallyldimethylammonium chloride) (PDADMAC). After coupling the nano-TiO2-coated microfluidic-based photocatalyst-assisted reduction device (the nano-TiO2-coated microfluidic-based PCARD) with high-performance liquid chromatography (HPLC) and inductively coupled plasma mass spectrometry (ICP-MS), a selective and sensitive, hyphenated system for Hg speciation was established. Validation procedures demonstrated that the method could be satisfactorily applied to the determination of mercury ions (Hg2+) and methylmercury ions (CH3Hg+) in both human urine and water samples. Remarkably, the zeta potential measured clearly indicated that the PDADMAC-capped nano-TiO2s with a predominance of positive charges indeed provided a steady force for firm attachment to the negatively charged device channel. The cause of the durability of the nano-TiO2-coated microfluidic-based PCARD was clarified thus.

Clinical Analysis of Sinistral Portal Hypertension.

Background: Sinistral portal hypertension (SPH) is the only type of portal hypertension that is entirely curable. However, it can easily cause varicose veins in the esophagus and/or stomach, as well as upper gastrointestinal hemorrhage. This study aimed to investigate the clinical characteristics and treatments of sinistral portal hypertension. Methods: All patients with pancreatic disease were included in this retrospective cohort study at the Affiliated Hospital of Southwest Medical University (Luzhou, China) from September 2019 to September 2021. The required information including the patient's demographics, serum laboratory indicators, imaging and endoscopy examinations, and clinical features were gathered and evaluated. The results were expressed as numbers and percentages. Results: Out of the 830 patients with pancreatic diseases, 61 (7.3%) developed SPH. The most common cause of SPH was acute pancreatitis (80.3%), followed by chronic pancreatitis (11.5%). The splenic vein was the most frequently affected vein in patients (45/61, 73.8%). The findings of the contrast-enhanced computed tomography (CECT) indicated that 51 cases (83.6%) had gastric fundal-body varices, and three cases had combined gastric and esophageal varices. In the perigastric collateral channel formation, gastroepiploic varices (43/61, 70.5%) most frequently occurred in patients with SPH. Splenomegaly was a prevalent manifestation in SPH patients (45.9%). Five cases had gastrointestinal variceal hemorrhage. Conclusion: SPH was associated with the patency of the splenic vein and the formation of distinctive perigastric collateral veins. Surgery and/or endoscopic treatment were recommended, particularly for patients who have experienced a significant amount of gastrointestinal bleeding and have failed conservative treatment.

In vivo pharmacokinetics of ginsenoside compound K mediated by gut microbiota.

Ginsenoside Compound K (GCK) is the main metabolite of natural protopanaxadiol ginsenosides with diverse pharmacological effects. Gut microbiota contributes to the biotransformation of GCK, while the effect of gut microbiota on the pharmacokinetics of GCK in vivo remains unclear. To illustrate the role of gut microbiota in GCK metabolism in vivo, a systematic investigation of the pharmacokinetics of GCK in specific pathogen free (SPF) and pseudo-germ-free (pseudo-GF) rats were conducted. Pseudo-GF rats were treated with non-absorbable antibiotics. Liquid chromatography tandem mass spectrometry (LC-MS/MS) was validated for the quantification of GCK in rat plasma. Compared with SPF rats, the plasma concentration of GCK significantly increased after the gut microbiota depleted. The results showed that GCK absorption slowed down, Tmax delayed by 3.5 h, AUC0-11 increased by 1.3 times, CLz/F decreased by 0.6 times in pseudo-GF rats, and Cmax was 1.6 times higher than that of normal rats. The data indicated that gut microbiota played an important role in the pharmacokinetics of GCK in vivo.

Stable and efficient CsPbI3 quantum-dot light-emitting diodes with strong quantum confinement.

Even though lead halide perovskite has been demonstrated as a promising optoelectronic material for next-generation display applications, achieving high-efficiency and stable pure-red (620~635 nm) emission to cover the full visible wavelength is still challenging. Here, we report perovskite light-emitting diodes emitting pure-red light at 628 nm achieving high external quantum efficiencies of 26.04%. The performance is attributed to successful synthesizing strongly confined CsPbI3 quantum dots with good stability. The strong binding 2-naphthalene sulfonic acid ligands are introduced after nucleation to suppress Ostwald ripening, meanwhile, ammonium hexafluorophosphate exchanges long chain ligands and avoids regrowth by strong binding during the purification process. Both ligands enhance the charge transport ability of CsPbI3 quantum dots. The state-of-the-art synthesis of pure red CsPbI3 quantum dots achieves 94% high quantum efficiency, which can maintain over 80% after 50 days, providing a method for synthesizing stable strong confined perovskite quantum dots.

Corrigendum: An in-cluster Sfp-type phosphopantetheinyl transferase instead of the holo-ACP synthase activates the granaticin biosynthesis under natural physiological conditions.

[This corrects the article DOI: 10.3389/fchem.2022.1112362.].

Identification and Functional Analysis of circRNAs during Goat Follicular Development.

Litter size is a crucial quantitative trait in animals, closely linked to follicular development. Circular RNA (circRNA), a type of single-stranded closed-loop endogenous RNA with stable expression, plays pivotal roles in various biological processes, yet its function in goat follicular development remains unclear. In this study, we collected large (follicle diameter > 3 mm) and small (1 mm < follicle diameter < 3 mm) follicles from black goats in the Chuanzhong region for circRNA sequencing, with the aim of elucidating the functional circRNAs that influence follicle development in goats. Differential analysis revealed that 17 circRNAs were upregulated in large follicles, and 28 circRNAs were upregulated in small follicles. Functional enrichment analysis revealed significant enrichment of pathways related to reproduction, including cellular response to follicle-stimulating hormone stimulus, the PI3K-Akt signaling pathway, the MAPK signaling pathway, and the Notch signaling pathway. Based on the ceRNA mechanism, 45 differentially expressed circRNAs were found to target and bind a total of 418 miRNAs, and an intercalation network including miR-324-3p (circRNA2497, circRNA5650), miR-202-5p (circRNA3333, circRNA5501), and miR-493-3p (circRNA4995, circRNA5508) was constructed. In addition, conservation analysis revealed that 2,239 circRNAs were conserved between goats and humans. Prediction of translation potential revealed that 154 circRNAs may potentially utilize both N6-methyladenosine (m6A) and internal ribosome entry site (IRES) translation mechanisms. Furthermore, the differential expression and circularization cleavage sites of five circRNAs were validated through RT-qPCR and DNA sequencing. Our study constructed a circRNA map in goat follicle development, offering a theoretical foundation for enhancing goat reproductive performance.

Retrospective assessment of short-term outcomes of robotic- versus laparoscopic-assisted duodenal diamond anastomosis in neonates.

OBJECTIVE: The purpose of this study was to retrospectively compare the short-term outcomes of robotic- (RAD) and laparoscopic-assisted duodenal diamond-shaped anastomosis (LAD) in neonates. METHODS: Neonates who underwent RAD (n = 30) or LAD (n = 38) between January 2019 and December 2022 were analyzed retrospectively. Major patient data were collected, including preoperative, intraoperative, and postoperative information. RESULTS: All patients were neonates below the age of 30 days weighing 4 kg. Thirty (44.1%) neonates underwent RAD and 38 neonates (55.9%) underwent LAD. Compared to the LAD group, the RAD group had a shorter intra-abdominal operation time (RAD, 60.0(50.0 ~ 70.0) min; LAD, 79.9(69.0 ~ 95.3) min; p < 0.001). There were no significant differences in immediate and 30-day complications between the two groups. CONCLUSIONS: RAD is safe and effective in neonates. Compared to traditional LAD, RAD showed comparable results.

Effect of desflurane maintenance on postoperative sleep quality in patients undergoing elective breast surgery: A non-inferiority randomized controlled trial.

BACKGROUND: Postoperative sleep disturbance (PSD) is prevalent in perioperative patients，and has significant impact on postoperative recovery and prognosis. The aim of this study was to investigate the effect of desflurane maintenance on postoperative sleep quality, in order to optimize patients' perioperative sleep management. METHOD: A total of 118 patients undergoing elective breast surgery were randomized to receive either desflurane-based volatile anesthesia (desflurane group) or propofol-based total intravenous anesthesia (propofol group) for anesthesia maintenance. The primary outcome was the quality of sleep, which was assessed by the Pittsburgh Sleep Quality Index (PSQI) on 3 days after operation (POD3). Secondary outcomes were PSQI on postoperative day 7 (POD7) and 30 (POD30), and postoperative anxiety, depression, and pain score, as well as objective sleep parameters including total sleep time (TST), WASO (Wakefulness after sleep onset), REM (Rapid eye movement) and NREM (Non-rapid Eye Movement) measured by Fitbit Charge 2TM during the initial 3 postoperative days. RESULTS: The global PSQI scores on POD3 in the desflurane group was non-inferior to that in the propofol group [mean (SD) 8.47 (3.46) vs. 7.65 (3.16); mean difference (95 % CI) 0.82 (-0.43, 2.07); p < 0.001 for non-inferiority]. There were no significant differences in PSQI scores on POD3 and POD7. In addition, the score of anxiety, depression, and pain on the 3rd, 7th, and 30th day after surgery have no significant differences between the propofol and the desflurane group, respectively. The postoperative NREM was higher in the desflurane group than that in the propofol group. CONCLUSION: The effects of desflurane-based volatile anesthesia maintenance on postoperative sleep quality is not inferior to that of propofol-based total intravenous anesthesia, and these two drugs may have different effects on the sleep structure. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04805775.

Preparation of Indolin-3-one-Containing 1,4-Naphthoquinone Derivatives via Organocatalytic Asymmetric Michael Addition Reaction.

This article explores the asymmetric Michael addition reaction of 2-hydroxy-1,4-naphthoquinone and indole-3-ones catalyzed by cinchona alkaloids. This strategy utilizes 2-hydroxy-1,4-naphthoquinone and easily prepared indole-3-one as substrates, resulting in the synthesis of 23 unprecedented indolin-3-ones bearing a 1,4-naphthoquinone unit at the C2 position of indole under simple and mild reaction conditions, with up to 88% yield, 98% ee, and >20:1 dr.

RNA epigenetic modifications in digestive tract cancers: Friends or foes.

Digestive tract cancers are among the most common malignancies worldwide and have high incidence and mortality rates. Thus, the discovery of more effective diagnostic and therapeutic targets is urgently required. The development of technologies to accurately detect RNA modification has led to the identification of numerous RNA chemical modifications in humans (epitranscriptomics) that are involved in the occurrence and development of digestive tract cancers. RNA modifications can cooperatively regulate gene expression to facilitate normal physiological functions of the digestive system. However, the dysfunction of relevant RNA-modifying enzymes ("writers," "erasers," and "readers") can lead to the development of digestive tract cancers. Consequently, targeting dysregulated enzyme activity could represent a potent therapeutic strategy for the treatment of digestive tract cancers. In this review, we summarize the most widely studied roles and mechanisms of RNA modifications (m6A, m1A, m5C, m7G, A-to-I editing, pseudouridine [Ψ]) in relation to digestive tract cancers, highlight the crosstalk between RNA modifications, and discuss their roles in the interactions between the digestive system and microbiota during carcinogenesis. The clinical significance of novel therapeutic methods based on RNA-modifying enzymes is also discussed. This review will help guide future research into digestive tract cancers that are resistant to current therapeutics.

A neuroendocrine tumor arising in a tailgut cyst: Case report and literature review.

INTRODUCTION AND IMPORTANCE: Cystic lesions in the retrorectal space include developmental abnormality, inflammatory process, and tumor-relevant cysts. Among them, the tailgut cyst is the most common lesion which is featured by the complex epithelium lining the wall. It is generally accepted that tailgut cysts are embryonic residues and are mostly benign, but there are also reports about malignant transformation and even metastasis. CASE PRESENTATION: A 44-year-old female complained a sacrococcygeal discomfort more than one year. The imaging diagnosis was an infectious cyst. After surgery, a solid region was defined in a cyst. Morphologically, the region was composed of bland epithelia forming glandular or ribbon-like structure, with round nuclei and fine chromatin. Immunohistochemically, the cells were positive for CK7, CD56 and synaptophysin. The Ki-67-positive cells were about 1 %. The final diagnosis is a low-grade neuroendocrine tumor arising in a tailgut cyst. The patient was living without recurrence by the follow-up of 20 months after surgery. CLINICAL DISCUSSION: By reviewing the previously reported NET arising from tailgut cysts, we summarized 29 cases of neuroendocrine neoplasms that reported detailed information, and the majority are women. We found that the higher-grade tumor presented a higher tendency of distant metastasis or recurrence after surgery. Complete resection and full evaluation by pathologists are necessary to get a correct diagnosis and avoid disease progression. CONCLUSION: We reported the rare case of NET G1 arising from a tailgut cyst and reviewed relevant reports, in order to broaden differential diagnoses when an isolated mass is identified in the retrorectal space.

Multi-omics analysis uncovered systemic lupus erythematosus and COVID-19 crosstalk.

BACKGROUND: Studies have highlighted a possible crosstalk between the pathogeneses of COVID-19 and systemic lupus erythematosus (SLE); however, the interactive mechanisms remain unclear. We aimed to elucidate the impact of COVID-19 on SLE using clinical information and the underlying mechanisms of both diseases. METHODS: RNA-seq datasets were used to identify shared hub gene signatures between COVID-19 and SLE, while genome-wide association study datasets were used to delineate the interaction mechanisms of the key signaling pathways. Finally, single-cell RNA-seq datasets were used to determine the primary target cells expressing the shared hub genes and key signaling pathways. RESULTS: COVID-19 may affect patients with SLE through hematologic involvement and exacerbated inflammatory responses. We identified 14 shared hub genes between COVID-19 and SLE that were significantly associated with interferon (IFN)-I/II. We also screened and obtained four core transcription factors related to these hub genes, confirming the regulatory role of the IFN-I/II-mediated Janus kinase/signal transducers and activators of transcription (JAK-STAT) signaling pathway on these hub genes. Further, SLE and COVID-19 can interact via IFN-I/II and IFN-I/II receptors, promoting the levels of monokines, including interleukin (IL)-6/10, tumor necrosis factor-α, and IFN-γ, and elevating the incidence rate and risk of cytokine release syndrome. Therefore, in SLE and COVID-19, both hub genes and core TFs are enriched within monocytes/macrophages. CONCLUSIONS: The interaction between SLE and COVID-19 promotes the activation of the IFN-I/II-triggered JAK-STAT signaling pathway in monocytes/macrophages. These findings provide a new direction and rationale for diagnosing and treating patients with SLE-COVID-19 comorbidity.

Silk fibroin biohydrogel composites for loading and ordered release of multiple active ingredients with enhanced bioactivity.

Bioactive hydrogels are currently receiving significant attention. In this study, silk fibroin tyramine-modified gelatin hydrogels (SF-TG) with varying degrees of tyramine root substitution were explored. The physicochemical property and biocompatibility of low degree of substitution tyramine-modified gelatin hydrogel (SF-LTG) and high degree of substitution tyramine-modified gelatin hydrogel (SF-HTG) were compared. The results showed that SF-LTG possessed better mechanical property and higher biocompatibility. Thus, SF-LTG was selected as a bioactive matrix and loaded with basic fibroblast growth factor (bFGF); subsequently, curcumin-coupled chitosan rods (CCCRs-EGF) enriched with epidermal growth factor (EGF) were added to obtain SF-LTG-bFGF@CCCRs-EGF hydrogels. The results showed that SF-LTG-bFGF@CCCRs-EGF retained the basic structural and mechanical properties of the SF-LTG matrix gel material and underwent multiple loading and orderly release with different activities while displaying antioxidant, anti-inflammatory, antimicrobial, and pro-cellular proliferation activities and orderly regulation of activity during wound healing. Therefore, the SF-LTG-bFGF@CCCRs-EGF hydrogel is of great value in healing complex wounds.

Clinical characteristics, treatment and efficacy of calcaneal osteomyelitis: A systematic review with synthesis analysis 1118 reported cases.

BACKGROUND: Calcaneal osteomyelitis (CO) still poses great challenges to orthopaedic surgeons due to unique anatomic and functional features of the calcaneus. This study summarized the current data regarding clinical characteristics, treatment and efficacy of CO, based on an analysis of literature-reported cases. MATERIALS AND METHODS: We searched the PubMed, Embase, and Cochrane Library databases to find English and Chinese studies reporting on CO patients between 2000 and 2021, with available data for synthesis analysis. The quality of the included studies was evaluated by the National Institutes of Health (NIH) assessment scale. Effective data were extracted and pooled for analysis. RESULTS: Altogether 198 studies involving 1118 patients were included, with a male-to-female ratio of 2.3 (724 males and 310 females). The median age at CO diagnosis was 46 years, with a median symptom duration of 3 months. Injury-related infections (524 cases) and diabetic foot infections (336 cases) were the two most common causes, with ulcer (468 cases) and wound sinus or exudation (209 cases) being the predominant symptoms. The overall positive culture rate was 80.2%, with polymicrobial infections accounting for 18.1%. Staphylococcus aureus was the most frequently detected pathogen (42.7%), with fungal-related infections isolated in 17 cases. Although most patients received surgical interventions (96.9%), the recurrence rate was 20.1%. The incidence of infection relapse following partial calcanectomy, total calcanectomy, debridement with implantation of local antibiotics, and debridement with or without flap or skin coverage were 31.7%, 45.0%, 16.8%, and 15.1%, respectively. The overall incidence of limb amputation was 12.4%, with all-cause and CO-related mortalities of 2.8% and 0.2%, separately. CONCLUSIONS: CO shared similar characteristics with extremity chronic osteomyelitis, primarily affecting young males, with trauma and diabetic foot as the leading causes and Staphylococcus aureus as the most frequently detected pathogen. Despite surgery being the primary treatment modality, clinical outcomes remained unsatisfactory, marked by high rates of infection recurrence and limb amputation.

SIG: Graph-Based Cancer Subtype Stratification With Gene Mutation Structural Information.

Somatic tumors have a high-dimensional, sparse, and small sample size nature, making cancer subtype stratification based on somatic genomic data a challenge. Current methods for improving cancer clustering performance focus on dimension reduction, integrating multi-omics data, or generating realistic samples, yet ignore the associations between mutated genes within the patient-gene matrix. We refer to these associations as gene mutation structural information, which implicitly includes cancer subtype information and can enhance subtype clustering. We introduce a novel method for cancer subtype clustering called SIG(Structural Information within Graph). As cancer is driven by a combination of genes, we establish associations between mutated genes within the same patient sample, pair by pair, and use a graph to represent them. An association between two mutated genes corresponds to an edge in the graph. We then merge these associations among all mutated genes to obtain a structural information graph, which enriches the gene network and improves its relevance to cancer clustering. We integrate the somatic tumor genome with the enriched gene network and propagate it to cluster patients with mutations in similar network regions. Our method achieves superior clustering performance compared to SOTA methods, as demonstrated by clustering experiments on ovarian and LUAD datasets. The code is available at https://github.com/ChangSIG/SIG.git.