From bench to bed: deep insights the tacrolimus-induced diabetes and gut microbiota dysbiosis.

The gut-liver axis is particularly vulnerable, and the alterations in gut microbiota composition have been linked to post-transplant complications. Liver transplantation is a life-saving procedure for patients with end-stage liver disease, but post-transplant complications are common and can significantly impact long-term outcomes. Tacrolimus is a widely used immunosuppressive agent in liver transplantation, primarily aimed at preventing graft rejection and promoting long-term graft survival.

Development of rare-earth upconversion luminescent nanoprobe for bisulfate sensing and imaging of drug-induced hepatotoxicity.

Abnormal levels of bisulfite in living organisms may cause respiratory diseases, cardiovascular diseases and even cancer. Rare-earth upconversion luminescent nanomaterials have anti-Stokes luminescence characteristics, excellent photostability and high chemical stability, while organic fluorescent probe has the advantages of the specific recognition groups. Thus, the combination of luminescent nanomaterials and an organic fluorescent probe can offer a novel approach to detect the content of HSO.

Genetic Risk and Prognosis of the First Incident Stroke Survivors: Findings from China Kadoorie Biobank and UK Biobank.

Background And Objectives: Stroke is known for its poor prognosis. Although genetic instruments have shown promise in stratifying first stroke risk in the general population, it is unknown whether they are associated with stroke prognosis. Our study aims to explore the role of genetic risk of stroke in the progression from stroke-free to first stroke and then to recurrent stroke, subsequent coronary heart disease (CHD), and death in China and the United Kingdom.

Gitelman syndrome: diagnostic challenges and therapeutic strategies.

Gitelman syndrome (GS), characterized as an autosomal recessive tubulopathy due to SLC12A3 mutations, disrupts the sodium-chloride cotransporter (NCC) within the renal distal convoluted tubule. This condition results in a clinical presentation marked by hypokalemia, hypomagnesemia, metabolic alkalosis, and hypocalciuria. Despite the well-defined biochemical characteristics associated with GS, achieving an accurate diagnosis can be formidable due to the variability in phenotypic expression and the potential for overlapping with other acquired electrolyte disorders.

Design, synthesis, and activity evaluation of Asiatic acid derivatives as Survivin inhibitors.

Asiatic acid, a triterpenoid isolated from Centella asiatica, putatively functions through inhibition of Survivin-a member of the Inhibitor of Apoptosis Protein (IAP) family that modulates tumor survival. Taking GDP366 and LQZ-7I, two Survivin inhibitors of preclinical stage, as reference compounds, two classes of novel Asiatic acid derivatives (24 compounds in total) were designed and synthesized. These compounds demonstrated favorable docking capabilities and binding modes with the three-dimensional crystal structure of Survivin.

Berberine promotes apoptosis and inhibits the migration of oral squamous carcinoma cells through inhibition of the RAGE/PI3K/AKT/mTOR pathway.

Given the high recurrence rate, elevated risk of metastasis, and drug resistance associated with oral squamous cell carcinoma (OSCC), the development of low - toxicity and highly efficient therapeutic agents has emerged as a top research priority. In this study, we conducted an in-depth investigation into the efficacy and underlying mechanism of berberine (BBR), a compound renowned for its broad anticancer activity, in the context of OSCC. Using network pharmacology, we identified 91 potential targets of BBR in OSCC, with SRC, PIK3CA, and CDC42 ranking among the top.

Assessing multiple abilities through process data in computer-based assessments: The multidimensional sequential response model (MSRM).

With the advent of computer-based assessment (CBA), process data have assumed an increasingly pivotal role in estimating examinees' latent abilities by capturing detailed records of their response processes. This study introduces the Multidimensional sequential response model (MSRM), a novel model for assessing multiple abilities through process data in computer-based cognitive and psychological assessments. A Bayesian estimation method for the MSRM is proposed and examined through a Monte Carlo simulation study across varying conditions.

Transcriptomic and Metabolomic Analyses Reveal Response Mechanisms of Sinonovacula Constricta to Saline-Alkalinity Stresses.

The razor clam (Sinonovacula constricta) is a key species in marine aquaculture, known for its wide salinity adaptation, and potential for cultivation in saline-alkaline water. Understanding its response mechanisms is crucial for expanding its farming into these regions. This study reveals the response mechanisms of S.

BiFC and FACS-based CRISPR screening revealed that QKI promotes PABPN1 LLPS in colorectal cancer cells.

Protein liquid-liquid phase separation (LLPS), a pivotal phenomenon intricately linked to cellular processes, is regulated by various other proteins. However, there is still a lack of high-throughput methods for screening protein regulators of LLPS in target proteins. Here, we developed a CRISPR/Cas9-based screening method to identify protein phase separation regulators by integrating bimolecular fluorescence complementation (BiFC) and fluorescence-activated cell sorting (FACS).

Polygenic risk scores for pan-cancer risk prediction in the Chinese population: A population-based cohort study based on the China Kadoorie Biobank.

Background: Polygenic risk scores (PRSs) have been extensively developed for cancer risk prediction in European populations, but their effectiveness in the Chinese population remains uncertain.

Methods And Findings: We constructed 80 PRSs for the 13 most common cancers using seven schemes and evaluated these PRSs in 100,219 participants from the China Kadoorie Biobank (CKB). The optimal PRSs with the highest discriminatory ability were used to define genetic risk, and their site-specific and cross-cancer associations were assessed.

E3 ligase SYVN1-mediated polyubiquitination of CPSF6 promotes alternative polyadenylation and antivirus effects of macrophages.

Transcriptome-wide alternative polyadenylation (APA) is involved in both innate and adaptive immune responses of immune cells. Downregulation of the CPSF6 protein, one of the 3' end-processing factors, mediates APA in macrophages with responses to virus infection and plays an important role in its anti-virus effect. However, the signaling pathway and molecular mechanism underlying the downregulation of the CPSF6 protein remain elusive.

USP4-mediated CENPF deubiquitylation regulated tumor metastasis in colorectal cancer.

Metastasis is a major challenge for colorectal cancer (CRC) treatment. In this study, we identified autophagy activation as a prognostic indicator in CRC and observed that the expression of key autophagy proteins is elevated in metastatic and recurrent cases. Our subsequent goal was to identify potential genes associated with the autophagy panel and assess their prognostic significance, biological roles, and mechanisms in CRC metastasis.

Effect of Long-Term Fine Particulate Matter Exposure on Lung Cancer Incidence and Mortality in Chinese Nonsmokers.

The association between fine particulate matter (particulate matter ⩽2.5 μm in aerodynamic diameter, PM) and lung cancer incidence in nonsmokers (LCINS) remains inconsistent. To investigate the association between long-term PM exposure and LCINS in a Chinese population and to assess the modifying effect of genetic factors.

Involvement of Melatonin, Oxidative Stress, and Inflammation in the Protective Mechanism of the Carotid Artery over the Torpor-Arousal Cycle of Ground Squirrels.

Hibernating mammals experience severe hemodynamic changes over the torpor-arousal cycle, with oxygen consumption reaching peaks during the early stage of torpor to re-enter arousal. Melatonin (MT) can improve mitochondrial function and reduce oxidative stress and inflammation. However, the regulatory mechanisms of MT action on the vascular protective function of hibernators are still unclear.

Effect of micro-granular activated carbon on bacteriophage MS2 removal and fouling control in flat-plate MBR.

Pathogenic microorganisms pose a severe risk to the aquatic environment and human health. Membrane bioreactors (MBRs) have attracted much attention due to their simultaneous biological treatment and virus retention, but membrane fouling is the main obstacle. This study explored the effect of micro-granular activated carbon (μGAC) on bacteriophage MS2 removal efficiency and membrane fouling in a flat-plate MBR.

A near-infrared frequency upconversion fluorescent probe for rapid and sensitive visual detection of sulfur dioxide.

Inflammation is a complex physiological response involving various cellular and molecular events. Sulfur dioxide (SO), which is usually in the form of HSO and SO under physiological conditions, plays a crucial role in the regulation of inflammation and diseases. Frequency upconversion luminescence (FUCL) can realize the unique anti-Stokes process of long-wavelength excitation to short-wavelength emission; thus, it is a highly promising optical method for imaging due to its deep tissue penetration, low photo-damage, .

Role of lifestyle factors on the development and long-term prognosis of pneumonia and cardiovascular disease in the Chinese population.

Background: Whether adherence to a healthy lifestyle is associated with a lower risk of developing pneumonia and a better long-term prognosis remains unclear. This study aimed to investigate associations of individual and combined lifestyle factors (LFs) with the incidence risk and long-term prognosis of pneumonia hospitalization.

Methods: Using data from the China Kadoorie Biobank study, we used the multistate models to investigate the role of five high-risk LFs, including smoking, excessive alcohol drinking, unhealthy dietary habits, physical inactivity, and unhealthy body shape, alone or in combination in the transitions from a generally healthy state at baseline to pneumonia hospitalization or cardiovascular disease (CVD, regarded as a reference outcome), and subsequently to mortality.

BAP1-mediated MAFF deubiquitylation regulates tumor growth and is associated with adverse outcomes in colorectal cancer.

Background: Despite improvements in colorectal cancer (CRC) treatment, the prognosis for advanced CRC patients remains poor. Disruption of protein stability is one of the important factors in cancer development and progression. In this study, we aim to identify and analyze novel dysregulated proteins in CRC, assessing their significance and the mechanisms.

Male Germ Cell Specification in Plants.

Germ cells (GCs) serve as indispensable carriers in both animals and plants, ensuring genetic continuity across generations. While it is generally acknowledged that the timing of germline segregation differs significantly between animals and plants, ongoing debates persist as new evidence continues to emerge. In this review, we delve into studies focusing on male germ cell specifications in plants, and we summarize the core gene regulatory circuits in germ cell specification, which show remarkable parallels to those governing meristem homeostasis.

Biothiols-activated near-infrared frequency up-conversion luminescence probe for early evaluation of drug-induced hepatotoxicity.

A novel biothiols-sensitive near-infrared (NIR) fluorescent probe RhDN based on a rhodamine skeleton was developed for early detection of drug-induced hepatotoxicity in living mice. RhDN can be used not only as a conventional large stokes shift fluorescent (FL) probe, but also as a kind of anti-Stokes frequency upconversion luminescence (FUCL) molecular probe, which represents a long wavelength excitation (808 nm) to short wavelength emission (760 nm), and response to Cys/Hcy/GSH with high sensitivity. Compared with traditional FL methods, the FUCL method exhibited a lower detection limit of Cys, Hcy, and GSH in 75.

Disruption of PABPN1 phase separation by SNRPD2 drives colorectal cancer cell proliferation and migration through promoting alternative polyadenylation of CTNNBIP1.

Generally shortened 3' UTR due to alternative polyadenylation (APA) is widely observed in cancer, but its regulation mechanisms for cancer are not well characterized. Here, with profiling of APA in colorectal cancer tissues and poly(A) signal editing, we firstly identified that the shortened 3' UTR of CTNNIBP1 in colorectal cancer promotes cell proliferation and migration. We found that liquid-liquid phase separation (LLPS) of PABPN1 is reduced albeit with higher expression in cancer, and the reduction of LLPS leads to the shortened 3' UTR of CTNNBIP1 and promotes cell proliferation and migration.