Global burden of lung cancer in women of childbearing age attributable to ambient particulate matter pollution: 1990-2021.

BACKGROUND: This study aimed to evaluate the global burden of lung cancer due to ambient particulate matter (PM) pollution in women of childbearing age from 1990 to 2021. METHODS: This was a secondary analysis utilizing data from the Global Burden of Disease (GBD) 2021, with a focus on the temporal trends of the lung cancer burden attributable to ambient PM2.5 among women of childbearing age. RESULTS: In 2021, the global mortality and disability-adjusted life years (DALYs) number of lung cancer burden attributable to ambient PM2.5 among women of childbearing age were approximately 5205 and 247,211, respectively. The rate of lung cancer attributable to ambient PM2.5 among women of childbearing age increased between 1990 and 2021, with the age-standardized mortality rate (ASMR) increasing from 0.22 (95% uncertainty interval [UI]; 0.13 to 0.33) to 0.25 (95% UI; 0.14 to 0.37; average annual percent change [AAPC] = 0.40) and the age-standardized DALYs rate (ASDR) increasing from 10.39 (95% UI; 5.96 to 15.72) to 12.06 (95% UI; 6.83 to 17.51; AAPC = 0.41). The middle sociodemographic index (SDI) region, East Asia, and China had the heaviest burden, while the high SDI region showed the highest decrease. ASMR and ASDR exhibited an inverted U-shaped relationship with the SDI. CONCLUSIONS: From 1990 to 2021, the lung cancer burden attributable to ambient PM2.5 among women of childbearing age exhibited an increasing trend. Furthermore, increasing attention should be paid to the middle SDI region, East Asia, and China, as ambient PM pollution remains a critical target for intervention.

Intelligent optimal control model of selection pressure for rapid culture of aerobic granular sludge based on machine learning and simulated annealing algorithm.

Aerobic Granular Sludge (AGS) has advantages over Activated sludge (AS) but faces challenges with long granulation periods. In this study, a novel grey-box model is devised to optimize the cultivation of AGS to shorten the formation time. This model is based on an existing white-box model. The modeling process starts with the application of four sensitivity analysis methods to assess the 12 model metrics selected. Subsequently, 12 prediction models were constructed by combining the six Machine learning (ML) algorithms and integrated algorithms, with the best performance selected (R2 = 0.98). Finally, an AGS selection pressure planning model was designed in conjunction with a simulated annealing (SA) algorithm to guide AGS training. The results demonstrate that AGS formation could be achieved within four days under the model's optimal control. Therefore, the establishment of this model provides a new technique for the cultivation of AGS.

Dissociated urethral plate Onlay and standard Onlay urethroplasty for mid-distal hypospadias: A comparative study.

BACKGROUND: Urethral plate (UP) reserved Onlay urethroplasty is currently used widely in mid-distal hypospadias. However, for children with 15-30° residual curvature after degloving, only dorsal tunica albuginea plication is performed to correct penile ventral curvature (VC), and long-term follow-up showed a high recurrence rate of penile curvature. We developed a modified Onlay urethroplasty, which dissociates the UP and completely removes the tissue beneath the UP to fully correct penile curvature. Furthermore, we compared it with the standard Onlay urethroplasty to explore its rationality and feasibility. METHODS: We prospectively collected clinical data from 68 children with hypospadias who underwent standard or modified Onlay urethroplasty between September 2019 and June 2021, and evaluated the interim outcomes to identify the complications between the two groups. Additionally, we conducted histological examination of the tissue beneath the UP. RESULTS: A total of 32 patients underwent modified Onlay urethroplasty. Intraoperative curvature measurements showed that 37.5% (12/32) of the patients had completely straightened their penis after UP dissection and removal of the fibrous tissue beneath it. A total of 36 patients underwent standard Onlay urethroplasty. Totally, five fistulas each were reported in the first and second groups, and the complication rates were 15.6% and 13.9%, respectively (P > 0.05). The histological results showed that the tissue below the UP contains a large amount of collagen, mainly type I collagen. CONCLUSION: The dissociated UP Onlay urethroplasty can maximally remove factors limiting penis growth and completely correct penile curvature, without increasing the incidence of postoperative complications. Therefore, we recommend the application of the improved Onlay urethroplasty in children with mid-distal hypospadias.

Nitrogen reducing mechanism by microporous aeration based on microbial population characteristics: water temperature factor.

The formation of black odour water is primarily attributed to the elevated concentration of organic pollutants, along with an excessive amount of nitrogen and phosphorus, ultimately leading to an anoxic aquatic environment. The water temperature influence mechanism on black-odorous water restoration by microporous aeration is still lacking depth study. This paper selected (15-18) ℃ (spring and autumn), (22-25) ℃ (summer), (8-11) ℃ (winter) as temperature conditions, and investigated temperature influence on nitrogen reduction. Researches showed that: (1) The removal rates of COD, NH4+-N and TN were significantly positively correlated with temperature (r = 0.99, 0.96, 0.97), the lowest removal rates were 83.16%, 95.68%, 58.7% ((8-11) ℃), the highest values were 92.67%, 98.27%, 70.96% ((22-25) ℃), respectively. (2) At a temperature range of 22-25°C, the microbial community exhibited the highest levels of abundance, diversity, and uniformity. Notably, Proteobacteria dominated this temperature range with a relative abundance of 79.72%. Furthermore, temperature positively correlated with the majority of dominant bacterial species, suggesting that conditions at 22-25°C are highly conducive to the growth of most bacterial communities. Among these, Limnohabitans, Alsobacter, and Candidatus_Aquirestis, which possess key functions in denitrification and nitrogen removal, displayed significantly higher abundances. It explains the positive correlation between temperature and removal rates of COD, TN and NH4+-N from microbial population's perspective. Thus, the best temperature for repairing black-smelly water is (22-25) ℃. This study provides technical reference for mechanism research and practical application of microporous aeration.

Ultrafast Synthesis of Transition Metal Phosphides in Air via Pulsed Laser Shock.

Transition metal phosphide nanoparticles (TMP NPs) represent a promising class of nanomaterials in the field of energy; however, a universal, time-saving, energy-efficient, and scalable synthesis method is currently lacking. Here, a facile synthesis approach is first introduced using a pulsed laser shock (PLS) process mediated by metal-organic frameworks, free of any inert gas protection, enabling the synthesis of diverse TMP NPs. Additionally, through thermodynamic calculations and experimental validation, the phase selection and competition behavior between phosphorus and oxygen have been elucidated, dictated by the redox potential and electronegativity. The resulting composites exhibit a balanced performance and extended durability. When employed as electrocatalysts for overall water splitting, the as-constructed electrolyzer achieves a low cell voltage of 1.54 V at a current density of 10 mA cm-2. This laser method for phosphide synthesis provides clear guidelines and holds potential for the preparation of nanomaterials applicable in catalysis, energy storage, biosensors, and other fields.

A metal-free cascaded process for efficient H2O2 photoproduction using conjugated carbonyl sites.

Carbon-based metal-free catalysts are promising green catalysts for photocatalysis and electrocatalysis due to their low cost and environmental friendliness. A key challenge in utilizing these catalysts is identifying their active sites, given their poor crystallinity and complex structures. Here we demonstrate the key structure of the double-bonded conjugated carbon group as a metal-free active site, enabling efficient O2 photoreduction to H2O2 through a cascaded water oxidation - O2 reduction process. Using ethylenediaminetetraacetic acid as a precursor, we synthesized various carbon-based photocatalysts and analyzed their structural evolution. Under the polymerization conditions of 260 °C to 400 °C, an N-ethyl-2-piperazinone-like structure was formed on the surface of the catalyst, resulting in high photocatalytic H2O2 photoproduction (2884.7 µmol g-1h-1) under visible light. A series of control experiments and theoretical calculations further confirm that the double-bond conjugated carbonyl structure is the key and universal feature of the active site of metal-free photocatalysts.

SIRT5 safeguards against T-2 toxin induced liver injury by repressing iron accumulation, oxidative stress, and the activation of NLRP3 inflammasome.

T-2 toxin, a highly toxic trichothecene mycotoxin widely found in food and feed, poses a significant threat to human health as well as livestock and poultry industry. Liver, being a crucial metabolic organ, is particularly susceptible to T-2 toxin induced damage characterized by inflammation and oxidative stress. Despite the role of Sirtuin 5 (SIRT5) in mitigating liver injury has been confirmed, its specific impact on T-2 toxin induced liver injury remains to be elucidated. The objective of this study was to investigate the protective role of SIRT5 against T-2 toxin induced liver injury in mice. Following the oral administration of 1 mg/kg.bw of T-2 toxin for 21 consecutive days to SIRT5 knockout (SIRT5-/-) and wild-type (WT) male mice, liver assessments were conducted. Our findings demonstrated that aggravated hepatic pathological injury was observed in SIRT5-/- mice, accompanied by elevated malondialdehyde (MDA) and Fe levels, as well as enhanced expression of glutathione peroxidase 4 (GPX4), NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1, Gasdermin-D (GSDMD), tumour necrosis factor-alpha (TNF-α), and interleukin-1beta (IL-1ß). These results indicated that SIRT5 alleviated hepatic structural damage and dysfunction, while inhibiting oxidative stress, iron accumulation, and NLRP3 inflammasome activation. Analysis revealed a positive correlation among NLRP3 inflammasome activation, iron accumulation, and oxidative stress. Overall, our study demonstrated that SIRT5 mitigated liver injury induced by T-2 toxin through inhibiting iron accumulation, oxidative stress, and NLRP3 inflammasome activation, providing novel insights into the management and prevention of T-2 toxin poisoning.

Single-cell transcriptome profiles the heterogeneity of tumor cells and microenvironments for different pathological endometrial cancer and identifies specific sensitive drugs.

Endometrial cancer (EC) is a highly heterogeneous malignancy characterized by varied pathology and prognoses, and the heterogeneity of its cancer cells and the tumor microenvironment (TME) remains poorly understood. We conducted single-cell RNA sequencing (scRNA-seq) on 18 EC samples, encompassing various pathological types to delineate their specific unique transcriptional landscapes. Cancer cells from diverse pathological sources displayed distinct hallmarks labeled as immune-modulating, proliferation-modulating, and metabolism-modulating cancer cells in uterine clear cell carcinomas (UCCC), well-differentiated endometrioid endometrial carcinomas (EEC-I), and uterine serous carcinomas (USC), respectively. Cancer cells from the UCCC exhibited the greatest heterogeneity. We also identified potential effective drugs and confirmed their effectiveness using patient-derived EC organoids for each pathological group. Regarding the TME, we observed that prognostically favorable CD8+ Tcyto and NK cells were prominent in normal endometrium, whereas CD4+ Treg, CD4+ Tex, and CD8+ Tex cells dominated the tumors. CXCL3+ macrophages associated with M2 signature and angiogenesis were exclusively found in tumors. Prognostically relevant epithelium-specific cancer-associated fibroblasts (eCAFs) and SOD2+ inflammatory CAFs (iCAFs) predominated in EEC-I and UCCC groups, respectively. We also validated the oncogenic effects of SOD2+ iCAFs in vitro. Our comprehensive study has yielded deeper insights into the pathogenesis of EC, potentially facilitating personalized treatments for its varied pathological types.

Gravity-driven membrane integrated with membrane distillation for efficient shale gas produced water treatment.

Substantial volumes of hazardous shale gas produced water (SGPW) generated in unconventional natural gas exploration. Membrane distillation (MD) is a promising approach for SGPW desalination, while membrane fouling, wetting, and permeate deterioration restrict MD application. The integration of gravity-driven membrane (GDM) with MD process was proposed to improve MD performance, and different pretreatment methods (i.e., oxidation, coagulation, and granular filtration) were systematically investigated. Results showed that pretreatment released GDM fouling and improved permeate quality by enrich certain microbes' community (e.g., Proteobacteria and Nitrosomonadaceae), greatly ensured the efficient desalination of MD. Pretreatment greatly influences GDM fouling layer morphology, leading to different flux performance. Thick/rough/hydrophilic fouling layer formed after coagulation, and thin/loose fouling layer formed after silica sand filtration improved GDM flux by 2.92 and 1.9 times, respectively. Moreover, the beneficial utilization of adsorption-biodegradation effects significantly enhanced GDM permeate quality. 100 % of ammonia and 53.99 % of UV254 were efficiently removed after zeolite filtration-GDM and granular activated carbon filtration-GDM, respectively. Compared to the surged conductivity (41.29 µS/cm) and severe flux decline (>82 %) under water recovery rate of 75 % observed in single MD for SGPW treatment, GDM economically controlled permeate conductivity (1.39-19.9 µS/cm) and MD fouling (flux decline=8.3 %-27.5 %). Exploring the mechanisms, the GDM-MD process has similarity with Janus MD membrane in SGPW treatment, significantly reduced MD fouling and wetting.

Unraveling the Genetic Susceptibility of Irritable Bowel Syndrome: integrative genome-wide analyses in 845,492 individuals: a diagnostic study.

BACKGROUND: Irritable bowel syndrome (IBS) significantly impacts individuals due to its prevalence and negative effect on quality of life. Current genome-wide association studies (GWAS) have only identified a small number of crucial single nucleotide polymorphisms (SNPs), not fully elucidating IBS's pathogenesis. OBJECTIVE: To identify genomic loci at which common genetic variation influence IBS susceptibility. METHODS: Combining independent cohorts that in total comprise 65,840 cases of IBS and 788,652 controls, we performed a meta-analysis of genome-wide association studies (GWAS) of IBS. We also carried out gene mapping and pathway enrichment to gain insights into the underlying genes and pathways through which the associated loci contribute to disease susceptibility. Furthermore, we performed transcriptome analysis to deepen our understanding. IBS risk models were developed by combining clinical/lifestyle risk factors with polygenic risk scores (PRS) derived from the GWAS meta-analysis. We detect the phenotype association for IBS utilizing PRS-based phenome-wide association (PheWAS) analyses, linkage disequilibrium score regression, and Mendelian randomization. RESULTS: The GWAS meta-analysis identified 10 IBS risk loci, seven of which were novel (rs12755507, rs34209273, rs34365748, rs67427799, rs2587363, rs13321176, rs1546559). Multiple methods identified nine promising IBS candidate gene (PRRC2A, COP1, CADM2, LRP1B, SUGT1, MED12L, P2RY14, PHF2, SHISA6) at 10 GWAS loci. Transcriptome validation also revealed differential expression of these genes. Phenome-wide associations between PRS-IBS and nine traits (neuroticism, diaphragmatic hernia, asthma, diverticulosis, cholelithiasis, depression, insomnia, COPD, and BMI) were identified. The six diseases (asthma, diaphragmatic hernia, diverticulosis, insomnia major depressive disorder and neuroticism) were found to show genetic association with IBS and only major depressive disorder and neuroticism were found to show causality with IBS. CONCLUSION: We identified seven novel risk loci for IBS and highlight the substantial influence on genetic risk harboured. Our findings offer novel insights into aetiology and phenotypic association of IBS and lay the foundation for therapeutic targets and interventional strategies.

Wideband finely tunable, ultralow-phase noise microwave generation in a Brillouin cavity.

A novel, to the best of our knowledge, approach to generate frequency-tunable microwave sources with low-phase-noise based on a Brillouin laser frequency comb is proposed and experimentally demonstrated. The Brillouin laser frequency comb is generated by combining stimulated Brillouin scattering, frequency shifting optical injection locking, modulation sideband optical injection locking (MSOIL), and four-wave mixing effects. By beating the generated comb lines, the microwave is generated with an extremely low-level phase noise of -120 dBc/Hz at a 10-kHz offset. The frequency of the microwave signal can be finely tuned in steps of a Brillouin cavity mode spacing (i.e., 2 MHz) and coarsely adjusted to integer times the applied RF signal frequency in the MSOIL unit. Remarkably, the phase noise of the microwave source can be kept at almost the same low level during the whole tuning process over the frequency range of 30-75 GHz. The proposed tunable low-phase-noise microwave generation approach has great potential applications in communications, radars, and metrology.

The complete genome sequence of the planctomycetotal bacterium Bremerella sp. P1 with abundant genes involved in polysaccharide degradation.

Isolated from intertidal sediment of the Yellow Sea, China, Bremerella sp. P1 putatively represents a novel species within the genus Bremerella of the family Pirellulaceae in the phylum Planctomycetota. The complete genome of strain P1 comprises a single circular chromosome with a size of 6,955,728 bp and a GC content of 55.26%. The genome contains 5772 protein-coding genes, 80 tRNA and 6 rRNA genes. A total of 147 CAZymes and 128 sulfatases have been identified from the genome of strain P1, indicating that the strain has the capability to degrade a wide range of polysaccharides. Moreover, a gene cluster related to bacterial microcompartments (BMCs) formation containing genes encoding the shell proteins and related enzymes to metabolize fucose or rhamnose is also found in the genome of strain P1. The genome of strain P1 represents the second complete one in the genus Bremerella, expanding the understanding of the physiological and metabolic characteristics, interspecies diversity, and ecological functions of the genus.

Immobilizing Ordered Oxophilic Indium Sites on Platinum Enabling Efficient Hydrogen Oxidation in Alkaline Electrolyte.

Addressing the sluggish kinetics in the alkaline hydrogen oxidation reaction (HOR) is a pivotal yet challenging step toward the commercialization of anion-exchange membrane fuel cells (AEMFCs). Here, we have successfully immobilized indium (In) atoms in an orderly fashion into platinum (Pt) nanoparticles supported by reduced graphene oxide (denoted as O-Pt3In/rGO), significantly enhancing alkaline HOR kinetics. We have revealed that the ordered atomic matrix enables uniform and optimized hydrogen binding energy (HBE), hydroxyl binding energy (OHBE), and carbon monoxide binding energy (COBE) across the catalyst. With a mass activity of 2.3066 A mg-1 at an overpotential of 50 mV, over 10 times greater than that of Pt/C, the catalyst also demonstrates admirable CO resistance and stability. Importantly, the AEMFC implementing this catalyst as the anode catalyst has achieved an impressive power output compared to Pt/C. This work not only highlights the significance of constructing ordered oxophilic sites for alkaline HOR but also sheds light on the design of well-structured catalysts for energy conversion.

Integrated metagenomic and metabolomic analysis reveals distinctive stage-specific gut-microbiome-derived metabolites in intracranial aneurysms.

OBJECTIVE: Our study aimed to explore the influence of gut microbiota and their metabolites on intracranial aneurysms (IA) progression and pinpoint-related metabolic biomarkers derived from the gut microbiome. DESIGN: We recruited 358 patients with unruptured IA (UIA) and 161 with ruptured IA (RIA) from two distinct geographical regions for conducting an integrated analysis of plasma metabolomics and faecal metagenomics. Machine learning algorithms were employed to develop a classifier model, subsequently validated in an independent cohort. Mouse models of IA were established to verify the potential role of the specific metabolite identified. RESULTS: Distinct shifts in taxonomic and functional profiles of gut microbiota and their related metabolites were observed in different IA stages. Notably, tryptophan metabolites, particularly indoxyl sulfate (IS), were significantly higher in plasma of RIA. Meanwhile, upregulated tryptophanase expression and indole-producing microbiota were observed in gut microbiome of RIA. A model harnessing gut-microbiome-derived tryptophan metabolites demonstrated remarkable efficacy in distinguishing RIA from UIA patients in the validation cohort (AUC=0.97). Gut microbiota depletion by antibiotics decreased plasma IS concentration, reduced IA formation and rupture in mice, and downregulated matrix metalloproteinase-9 expression in aneurysmal walls with elastin degradation reduction. Supplement of IS reversed the effect of gut microbiota depletion. CONCLUSION: Our investigation highlights the potential of gut-microbiome-derived tryptophan metabolites as biomarkers for distinguishing RIA from UIA patients. The findings suggest a novel pathogenic role for gut-microbiome-derived IS in elastin degradation in the IA wall leading to the rupture of IA.

Strain- and Electron Doping-Induced In-Plane Spin Orientation at Room Temperature in Single-Layer CrTe2.

Ferromagnets with a Curie temperature surpassing room temperature (RT) are highly sought after for advancing planar spintronics. The ultrathin CrTe2 is proposed as a promising two-dimensional (2D) ferromagnet with a Curie temperature above 300 K. However, its single-layer film is highly susceptible to specific external perturbations, leading to variable magnetic features depending on the environment. The magnetic ordering of single-layer CrTe2 remains a topic of debate, and experimental confirmation of ferromagnetic order at RT is still pending. In our study, we utilized molecular beam epitaxy to create a single-layer 1T-CrTe2 on bilayer graphene, demonstrating ferromagnetism above 300 K with in-plane magnetization through superconducting quantum interference devices (SQUID) measurements. Our density functional theory (DFT) calculations suggest that the ferromagnetic properties stem from epitaxial strain, which increases the distance between adjacent Cr atoms within the layer by about 1.6% and enhances the Cr-Te-Cr angle by approximately 1.6°. Due to its interaction with the graphene substrate, the magnetic moment transitions from an out-of-plane to an in-plane orientation, while electronic doping exceeds 1.5 e/u.c. Combining DFT calculations with in situ scanning tunneling microscopy (STM) characterizations allowed us to determine the configuration of the CrTe2 single layer on graphene. This discovery presents the first experimental proof of ferromagnetic order in single-layer CrTe2 with a Curie temperature above RT, laying the groundwork for future applications of CrTe2 single-layer-based spintronic devices.

Linearly Polarized Broadband Emission and Multiwavelength Lasing in Solution-Processed Quantum Dots.

A miniature laser with linear polarization is a long sought-after component of photonic integrated circuits. In particular, for multiwavelength polarization lasers, it supports simultaneous access to multiple, widely varying laser wavelengths in a small spatial region, which is of great significance for advancing applications such as optical computing, optical storage, and optical sensing. However, there is a trade-off between the size of small-scale lasers and laser performance, and multiwavelength co-gain of laser media and multicavity micromachining in the process of laser miniaturization remain as significant challenges. Herein, room-temperature linearly polarized multiwavelength lasers in the visible and near-infrared wavelength ranges are demonstrated, by fabricating random cavities scattered with silica in an Er-doped Cs2Ag0.4Na0.6In0.98Bi0.02Cl6 double-perovskite quantum dots gain membrane. By regulating the local symmetry and enabling effective energy transfer in nanocrystals, multiwavelength lasers with ultralow thresholds are achieved at room temperature. The maximum degree of polarization reaches 0.89. With their advantages in terms of miniaturization, ultralow power consumption, and adaptability for integration, these lasers offer a prospective light source for future photonic integrated circuits aimed at high-capacity optical applications.

Alert for pharynx-centered gastrointestinal and respiratory cross-infection and cryptic cross-transmission routes of 2019-nCoV.

We proposed that the pharynx, as a common organ of the respiratory and digestive tracts, may be a respiratory and digestive tract cross cryptic transmission pathway for 2019-nCoV infection from the nasal cavities to the pharynx and lung, then to nasal cavities by aerosol (respiratory route) to the pharynx and the gastrointestinal tract, then to the oral cavity by feces (fecal-oral route) and to pharynx, lungs, or gastrointestinal tract.

Investigating shared genetic architecture between inflammatory bowel diseases and primary biliary cholangitis.

Background & Aims: Inflammatory bowel disease (IBD) is commonly associated with extraintestinal complications, including autoimmune liver disease. The co-occurrence of IBD and primary biliary cholangitis (PBC) has been increasingly observed, but the underlying relationship between these conditions remains unclear. Methods: Using summary statistics from genome-wide association studies (GWAS), we investigated the causal effects between PBC and IBD, including Crohn's disease (CD) and ulcerative colitis (UC). We also analyzed the shared genetic architecture between IBD and PBC using data from GWAS, bulk-tissue RNA sequencing, and single cell RNA sequencing, and explored potential functional genes. Result: There was a strong positive genetic correlation between PBC and IBD (linkage disequilibrium score regression: rg = 0.2249, p = 3.38 × 10-5). Cross-trait analysis yielded 10 shared-risk single nucleotide polymorphisms (SNPs), as well as nine novel SNPs, which were associated with both traits. Using Mendelian randomization, a stable causal effect was established of PBC on IBD. Genetically predicted PBC was found to have a risk effect on IBD (1.105; 95% CI: 1.058-1.15; p = 1.16 × 10-10), but not vice versa. Shared tissue-specific heritability enrichment was identified for PBC and IBD (including CD and UC) in lung, spleen, and whole-blood samples. Furthermore, shared enrichment was observed of specific cell types (T cells, B cells, and natural killer cells) and their subtypes. Nine functional genes were identified based on summary statistics-based Mendelian randomization. Conclusions: This study detected shared genetic architecture between IBD and PBC and demonstrated a stable causal relationship of genetically predicted PBC on the risk of IBD. These findings shed light on the biological basis of comorbidity between IBD and PBC, and have important implications for intervention and treatment targets of these two diseases simultaneously. Impact and Implications: The discovery of novel shared single nucleotide polymorphisms (SNPs) and functional genes provides insights into the common targets between inflammatory bowel disease (IBD) and primary biliary cholangitis (PBC), serving as a basis for new drug development and contributing to the study of disease pathogenesis. Additionally, the established significant causality and genetic correlation underscore the importance of clinical intervention in preventing the comorbidity of IBD and PBC. The enrichment of SNP heritability in specific tissues and cell types reveals the role of immune factors in the potential disease mechanisms shared between IBD and PBC. This stimulates further research on potential interventions and could lead to the development of new targets for immune-based therapies.

Parathyroid Hormone is Negatively Correlated with Glycated Hemoglobin in Newly Diagnosed Type 2 Diabetic Patients.

Objective: The growing evidence shows that parathyroid hormone (PTH) may affect glucose metabolism. However, the relationship between them is still controversial among diabetic patients. The current study aimed to investigate the relationship between PTH and glucose metabolism in the patients with newly diagnosed type 2 diabetes (T2D). Methods: A total of 532 participants, including 387 patients with newly diagnosed T2D and 145 healthy controls, were recruited in the present study. PTH and metabolic parameters were measured in all participants. Results: The PTH levels were significantly lower in the newly diagnosed T2D patients compared with the control group (35.10 (25.90, 47.20) vs. 47.15 (35.83, 58.65) pg/ml, P < 0.001). The T2D patients with a higher glycated hemoglobin (HbA1c) tertile had lower PTH levels than the patients with a lower HbA1c tertile (32.90 (24.85, 41.40) vs. 37.50 (26.10, 54.55) pg/ml, P < 0.001). Spearman correlation analysis showed that PTH was positively correlated with the body mass index (BMI), fasting insulin (FINS), homeostasis model assessment of ß-cell function (HOMA-ß), and homeostasis model assessment of insulin resistance (HOMA-IR) and negatively correlated with HbA1c, blood calcium (Ca), blood phosphorus (P), and 25-hydroxyvitamin D3 (25-OH-D3). Multiple linear regression analysis demonstrated that PTH was significantly associated with HbA1c (ß = -1.475, P=0.003) and HOMA-ß (ß = 0.090, P=0.001) after adjusting for age, sex, BMI, season, 25-OH-D3, Ca, and P. Conclusion: PTH was negatively correlated with HbA1c in the newly diagnosed T2D patients. Our results suggested that the PTH level within the reference range is related to islet ß-cell function and hyperglycemia.