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BackgroundObservational studies have reported associations between Barrett's esophagus (BE) and obstructive sleep apnea syndrome (OSAS), but the causal relationship remained unclear due to potential confounding biases. Our study aimed to elucidate this causal relationship by deploying a two-sample Mendelian randomization (MR) methodology.MethodsInstrumental variables (IVs) for Barrett's esophagus were obtained from a public database that comprised 13,358 cases and 43,071 controls. To investigate OSAS, we utilized summary statistics from a comprehensive genome-wide association study (GWAS) encompassing 38,998 cases of OSAS and 336,659 controls. Our MR analyses adopted multiple techniques, including inverse variance weighted (IVW), weighted median, weighted mode, MR-Egger, and simple mode.ResultsThe IVW analysis established a causal relationship between Barrett's esophagus and OSAS, with an odds ratio (OR) of 1.19 and a 95% confidence interval (CI) of 1.11–1.28 (p = 8.88E-07). Furthermore, OSAS was identified as a contributing factor to the onset of Barrett's esophagus, with an OR of 1.44 and a 95% CI of 1.33–1.57 (p = 7.74E-19). Notably, the MR–Egger intercept test found no evidence of directional pleiotropy (p > 0.05).ConclusionThis study identifies a potential association between BE and an increased occurrence of OSAS, as well as the reverse relationship. These insights could influence future screening protocols and prevention strategies for both conditions.

Hemophagocytic lymphohistiocytosis (HLH) is a rare histiocytic disorder characterized by reactive hyperplasia of the mononuclear phagocytic system, which is primarily caused by dysfunction of cytotoxic killer cells and natural killer cells, leading to antigen clearance barriers and the overactivation of the mononuclear phagocytic system due to continuous antigen stimulation. HLH encompasses a group of clinical syndromes marked by the overproduction of inflammatory cytokines. A 68-year-old Chinese man presented with persistent fever, chills, nausea, and vomiting; the patient had no history of any underlying conditions. Laboratory investigations revealed decreased levels of red blood cells, white blood cells, and platelets, along with reduced natural killer cell activity, increased CD25, hyperferritinemia, and the detection of Rickettsia DNA in his blood, meeting the diagnostic criteria of the Histiocyte Society HLH-2004 guidelines. The patient was treated with antibiotics, improving anemia, glucocorticoid therapy, and continuous renal replacement therapy (CRRT), temporarily improving his condition. However, the patient died after 2 years from chronic renal failure caused by septic shock.

BackgroundCandida albicans is a commensal yeast that may cause life-threatening infections. Studies have shown that the cytochrome b-c1 complex subunit 7 gene (QCR7) of C. albicans encodes a protein that forms a component of the mitochondrial electron transport chain complex III, making it an important target for studying the virulence of this yeast. However, to the best of our knowledge, the functions of QCR7 have not yet been characterized.MethodsA QCR7 knockout strain was constructed using SN152, and BALb/c mice were used as model animals to determine the role of QCR7 in the virulence of C. albicans. Subsequently, the effects of QCR7 on mitochondrial functions and use of carbon sources were investigated. Next, its mutant biofilm formation and hyphal growth maintenance were compared with those of the wild type. Furthermore, the transcriptome of the qcr7Δ/Δ mutant was compared with that of the WT strain to explore pathogenic mechanisms.ResultsDefective QCR7 reduced recruitment of inflammatory cells and attenuated the virulence of C. albicans infection in vivo. Furthermore, the mutant influenced the use of multiple alternative carbon sources that exist in several host niches (GlcNAc, lactic acid, and amino acid, etc.). Moreover, it led to mitochondrial dysfunction. Furthermore, the QCR7 knockout strain showed defects in biofilm formation or the maintenance of filamentous growth. The overexpression of cell-surface-associated genes (HWP1, YWP1, XOG1, and SAP6) can restore defective virulence phenotypes and the carbon-source utilization of qcr7Δ/Δ.ConclusionThis study provides new insights into the mitochondria-based metabolism of C. albicans, accounting for its virulence and the use of variable carbon sources that promote C. albicans to colonize host niches.

Resistance to thyroid hormone beta (RTHβ) is an autosomal dominant hereditary disorder that is difficult to diagnose because of its rarity and variable clinical features, which are caused by mutations in the thyroid hormone receptor beta (THRB) gene. Recent studies have indicated a close association between THRB mutations and human cancers, but the mechanistic role of THRB mutations in carcinogenesis is unknown. Herein, we report two cases of RTHβ coexisting with papillary thyroid carcinoma (PTC) and their follow-up results. Two female patients presented with elevated serum thyroid hormone levels and nonsuppressed thyrotropin (TSH). Genetic analysis showed that each patient had a THRB gene mutation (p.P453T and p. R320H). Based on the results of ultrasound-guided fine-needle aspiration biopsy, the thyroid nodules were suspected to be PTC. Intraoperative pathology confirmed that the two patients had PTC with multifocal carcinoma of both lobes. One patient underwent total thyroidectomy and central lymph node dissection, and the other underwent total thyroidectomy alone. Following surgery, large doses of levothyroxine were administered to suppress TSH levels and prevent recurrent or persistent disease. However, it is difficult to continually suppress TSH levels below the upper limit of the normal range. To date, the two patients have experienced no recurrence of PTC on ultrasound.

BackgroundHand-foot-mouth disease (HFMD) is caused by a group of enteroviruses (EVs) and has a high incidence in children; some subtypes had high mortalities in children. The subtypes of HFMD had a different incidence across seasons. Thereby, we suspect that the infection of HFMD is varied by meteorological factors. However, studies examining serotype-specific associations between meteorological factors and HFMD incidence were rare.MethodsWe obtained all HFMD cases that occurred from 1 January 2010 to 31 December 2018 in Zhejiang province from the China Information System for Disease Control and Prevention (CISDCP). Daily meteorological data for Zhejiang province were provided by the China Methodological Data Sharing Service System and linked to HFMD cases based on residential addresses and dates of onset. The associations between meteorological factors and HFMDs were examined using distributed lag non-linear models (DLNMs) for each serotype.ResultsOverall, the incidences of all HFMD cases were increasing in study years, while the number of severe and fatality cases were decreasing. The dominant serotypes varied by study year. The association between temperature and incidence of both CVA16 and EV71 serotypes showed an inverted U shape. The risk ratio for CVA16 was increasing when temperature is 11–25°C, reaching the maximum RR at 18°C and humidity above 77% can promote the occurrence with CVA16, and temperature between 11 and 32°C with the maximum RR at 21°C and relative humidity above 77% are risk conditions of the occurrence of HFMD associated with EV71. For other enteroviruses causing HFMD, temperature above 11°C and humidity above 76% have a risk effect. CVA16, EV71, and all enteroviruses of HFMD have a maximum effect on lag day 0, and temperature is 35, 34, and 33°C respectively, while the enteroviruses of HFMD other than EV71 and CVA16 has a maximum effect when the temperature is 33°C and the lag time is 7 days.ConclusionThis study shows that meteorological factors have an effect on the occurrence of different HFMD serotypes. Local control strategies for public health should be taken in time to prevent and reduce the risk of HFMD while the weather is getting warmer and wetter.

Climate models often predict that more extreme precipitation events will occur in arid and semiarid regions, where plant phenology is particularly sensitive to precipitation changes. To understand how increases in precipitation affect plant phenology, this study conducted a manipulative field experiment in a desert ecosystem of northwest China. In this study, a long-term in situ water addition experiment was conducted in a temperate desert in northwestern China. The following five treatments were used: natural rain plus an additional 0, 25, 50, 75, and 100% of the local mean annual precipitation. A series of phenological events, including leaf unfolding (onset, 30%, 50%, and end of leaf unfolding), cessation of new branch elongation (30, 50, and 90%), and leaf coloration (80% of leaves turned yellow), of the locally dominant shrub Nitraria tangutorum were observed from 2012 to 2018. The results showed that on average, over the seven-year-study and in all treatments water addition treatments advanced the spring phenology (30% of leaf unfolding) by 1.29–3.00 days, but delayed the autumn phenology (80% of leaves turned yellow) by 1.18–11.82 days. Therefore, the length of the growing season was prolonged by 2.11–13.68 days, and autumn phenology contributed more than spring phenology. In addition, water addition treatments delayed the cessation of new branch elongation (90%) by 5.82–12.61 days, and nonlinear relationships were found between the leaves yellowing (80% of leaves) and the amount of watering. Linear relationships were found between the cessation of new branch elongation (90%), the length of the growing season, and amount of water addition. The two response patterns to water increase indicated that predictions of phenological events in the future should not be based on one trend only.

The stringent regulatory network of cellulase gene expression in the filamentous fungus Trichoderma reesei involves multiple transcriptional regulators. However, identification and mechanistic investigation of these regulators are still insufficient. Here, we identified a novel transcriptional regulator, CLP1, a plant homeo domain (PHD) Protein that participates in regulating T. reesei cellulase gene expression. Phylogenetic analyses demonstrated that CLP1 homologs are widely distributed in filamentous fungi including Trichoderma, Penicillium, Fusarium, Neurospora, and Aspergillus species. We demonstrated that CLP1 is a nuclear protein and lack of CLP1 significantly impaired the induced expression of cellulase genes. ChIP experiments showed CLP1 binding to the cellulase gene promoters specifically under cellulose conditions and compromised XYR1 occupancy on the same promoters in the absence of CLP1 at the early induction stage. XYR1 overexpression fully rescued the defect in cellulase production but not the defect in conidia formation in the clp1 null mutant. Further analysis showed that the PHD is required for the CLP1 appropriate subcellular localization as well as the induced cellulase gene expression and conidiation. Taken together, these data demonstrated an important role of CLP1 in the regulation of cellulase and xylanase gene expression in T. reesei.