The translocation activity of Rad54 reduces crossover outcomes during homologous recombination.

Homologous recombination (HR) is a template-based DNA double-strand break repair pathway that requires the selection of an appropriate DNA sequence to facilitate repair. Selection occurs during a homology search that must be executed rapidly and with high fidelity. Failure to efficiently perform the homology search can result in complex intermediates that generate genomic rearrangements, a hallmark of human cancers. Rad54 is an ATP dependent DNA motor protein that functions during the homology search by regulating the recombinase Rad51. How this regulation reduces genomic exchanges is currently unknown. To better understand how Rad54 can reduce these outcomes, we evaluated several amino acid mutations in Rad54 that were identified in the COSMIC database. COSMIC is a collection of amino acid mutations identified in human cancers. These substitutions led to reduced Rad54 function and the discovery of a conserved motif in Rad54. Through genetic, biochemical and single-molecule approaches, we show that disruption of this motif leads to failure in stabilizing early strand invasion intermediates, causing increased crossovers between homologous chromosomes. Our study also suggests that the translocation rate of Rad54 is a determinant in balancing genetic exchange. The latch domain's conservation implies an interaction likely fundamental to eukaryotic biology.

Large-Substrate-Terrace Confined Growth of Arrayed Ultrathin PtSe2 Ribbons on Step-Bunched Vicinal Au(001) Facets Toward Electrocatalytic Applications.

Ultrathin PtSe2 ribbons can host spin-polarized edge states and distinct edge electrocatalytic activity, emerging as a promising candidate for versatile applications in various fields. However, the direct synthesis is still challenging and the growth mechanism is still unclear. Herein, the arrayed growth of ultrathin PtSe2 ribbons on bunched vicinal Au(001) facets, via a facile chemical vapor deposition (CVD) route is reported. The ultrathin PtSe2 flakes can transform from traditional irregular shapes to desired ribbon shapes by increasing the height of bunched and unidirectionally oriented Au steps (with step height hstep) is found. This crossover, occurring at hstep ≈ 3.0 nm, defines the tailored growth from step-flow to single-terrace-confined modes, as validated by density functional theory calculations of the different system energies. On the millimeter-scale single-crystal Au(001) films with aligned steps, the arrayed ultrathin PtSe2 ribbons with tunable width of ≈20-1000 nm, which are then served as prototype electrocatalysts for hydrogen evolution reaction (HER) is achieved. This work should represent a huge leap in the direct synthesis and the mechanism exploration of arrayed ultrathin transition-metal dichalcogenides (TMDCs) ribbons, which should stimulate further explorations of the edge-related physical properties and practical applications.

Global research trend and hotspot in the low FODMAP diet: a bibliometric analysis.

BACKGROUND: According to national guidelines, a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) is a second-line therapy option for irritable bowel syndrome (IBS) and improves functional intestinal symptoms. Numerous noteworthy results have been published in this field over the past fifteen years. This study aims to analyze the global research trend and hotspot of the low FODMAP diet research, and provide a comprehensive perspective and direction for researchers. METHODS: The Science Citation Index-Expanded of the Web of Science Core Collection (WoSCC) was used to identify low FODMAP diet-related articles and reviews. Three bibliometric programs (CiteSpace, VOSviewer, Scimago Graphic) were utilized to analyze and visualize the annual publications, authors, countries, institutions, journals, citations, and keywords. RESULTS: In total, 843 documents related to the low FODMAP diet research were published in 227 journals by 3,343 authors in 1,233 institutions from 59 countries. The United States, which was the most engaged nation in international collaboration, had the largest annual production and the fastest growth. The most productive organization was Monash University, and the most fruitful researcher was Gibson PR. Nutrients ranked first in terms of the number of published documents. The article "A diet low in FODMAPs reduces symptoms of irritable bowel syndrome" (Halmos EP, 2014) received the most co-citations. Keywords that appear frequently in the literature mainly involve two main aspects: the clinical efficacy evaluation and mechanism exploration of the low FODMAP diet. The term "gut microbiota" stands out as the most prominent keyword among the burst keywords that have remained prevalent till date. CONCLUSION: The restriction stage of the low FODMAP diet is superior to other dietary therapies for IBS in terms of symptom response, but it has a negative impact on the abundance of gut Bifidobacteria and diet quality. Identification of biomarkers to predict response to the low FODMAP diet is of great interest and has become the current research hotspot.

Influence of Zr Microalloying on the Microstructure and Room-/High-Temperature Mechanical Properties of an Al-Cu-Mn-Fe Alloy.

Here, 0.3 wt.%Zr was introduced in an Al-4 wt.%Cu-0.5 wt.%Mn-0.1 wt.%Fe alloy to investigate its influence on the microstructure and mechanical properties of the alloy. The microstructures of both as-cast and T6-treated Al-Cu-Mn-Fe (ACMF) and Al-Cu-Mn-Fe-Zr (ACMFZ) alloys were analyzed. The intermetallic compounds formed through the casting procedure include Al2Cu and Al7Cu2Fe, and the Al2Cu phase dissolves into the matrix and re-precipitates as θ' phase during the T6 process. The introduction of Zr results in the precipitation of L12-Al3Zr nanometric precipitates after T6, while the θ' precipitates in ACMFZ alloy are much finer than those in ACMF alloy. The L12-Al3Zr precipitates were found coherently located with θ', which was assumed beneficial for stabilizing the θ' precipitates during the high-temperature tensile process. The tensile properties of ACMF and ACMFZ alloys at room temperature and elevated temperatures (200, 300, and 400 °C) were tested. Especially, the yield strength of ACMFZ alloys can reach 128 MPa and 65 MPa at 300 °C and 400 °C, respectively, which are 31% and 33% higher than those of ACMF alloys. The strengthening mechanisms of grain size, L12-Al3Zr, and θ' precipitates on the tensile properties were discussed. This work may be referred to for designing Al-Cu alloys for application in high-temperature fields.

Chemical vapor deposition growth of graphene and other nanomaterials with 3D architectures towards electrocatalysis and secondary battery-related applications.

Recently, two-dimensional (2D) layered materials, such as graphene and transition metal dichalcogenides (TMDCs), have garnered a lot of attention in energy storage/conversion-related fields due to their novel physical and chemical properties. Constructing flat graphene and TMDCs nanosheets into 3D architectures can significantly increase their exposed surface area and prevent the restacking of adjacent 2D layers, thus dramatically promoting their applications in various energy-related fields. Chemical Vapor Deposition (CVD) is a low-cost, facile, and scalable method, which has been widely employed to produce high-quality graphene and TMDCs nanosheets with 3D architectures. During the CVD process, the morphologies and properties of the 3D architectures of such 2D materials can be designed by selecting substrates with different compositions, stacking geometries, and micro-structures. In this review, we focus on the recent advances in the CVD synthesis of graphene, TMDCs, and their hybrids with 3D architectures on different 3D-structured substrates, as well as their applications in the electrocatalytic hydrogen evolution reaction (HER) and various secondary batteries. In addition, the challenges and future prospects for the CVD synthesis and energy-related applications of these unique layered materials will also be discussed.

Willed Attentional Selection of Visual Features: An EEG Study.

Visual selective attention studies generally tend to apply cuing paradigms to instructively direct observers' attention to certain locations, features or objects. However, in real situations, attention in humans often flows spontaneously without any specific instructions. Recently, a concept named "willed attention" was raised in visuospatial attention, in which participants are free to make volitional attention decisions. Several ERP components during willed attention were found, along with a perspective that ongoing alpha activity may bias the subsequent attentional choice. However, it remains unclear whether similar neural mechanisms exist in feature- or object-based willed attention. Here, we included choice cues and instruct cues in a feature-based selective attention paradigm, allowing participants to freely choose or to be instructed to attend a color for the subsequent target detection task. Pre-cue ongoing alpha oscillations, cue-evoked potentials and target-related steady-state visual evoked potentials (SSVEPs) were simultaneously measured as markers of attentional processing. As expected, SSVEP responses were similarly modulated by attention between choice and instruct cue trials. Similar to the case of spatial attention, a willed-attention component (Willed Attention Component, WAC) was isolated during the cue-related choice period by comparing choice and instruct cues. However, pre-cue ongoing alpha oscillations did not predict the color choice (yellow vs blue), as indicated by the chance level decoding accuracy (50%). Overall, our results revealed both similarities and differences between spatial and feature-based willed attention, and thus extended the understanding toward the neural mechanisms of volitional attention.

Long non-coding RNA PWRN1 affects ovarian follicular development by regulating the function of granulosa cells.

RESEARCH QUESTION: What is the role of Prader-Willi region non-protein coding RNA 1 (PWRN1) in ovarian follicular development and its molecular mechanism? DESIGN: The expression and localization of PWRN1 were detected in granulosa cells from patients with different ovarian functions, and the effect of interfering with PWRN1 expression on cell function was detected by culturing granulosa cells in vitro. Furthermore, the effects of interfering with PWRN1 expression on ovarian function of female mice were explored through in-vitro and in-vivo experiments. RESULTS: The expression of PWRN1 was significantly lower in granulosa cells derived from patients with diminished ovarian reserve (DOR) compared with patients with normal ovarian function. By in-vitro culturing of primary granulosa cells or the KGN cell line, the results showed that the downregulation of PWRN1 promoted granulosa cell apoptosis, caused cell cycle arrested in S-phase, generated high levels of autophagy and led to significant decrease in steroidogenic capacity, including inhibition of oestradiol and progesterone production. In addition, SIRT1 overexpression could partially reverse the inhibitory effect of PWRN1 downregulation on cell proliferation. The results of in-vitro culturing of newborn mouse ovary showed that the downregulation of PWRN1 could slow down the early follicular development. Further, by injecting AAV-sh-PWRN1 in mouse ovarian bursa, the oestrous cycle of mouse was affected, and the number of oocytes retrieved after ovulation induction and embryos implanted after mating was significantly reduced. CONCLUSION: This study systematically elucidated the novel mechanism by which lncRNA PWRN1 participates in the regulation of granulosa cell function and follicular development.

Ocular trauma from Lawn mower accidents: Clinical insights, visual outcomes and microbial profiles.

AIMS: To characterize the clinical features of ocular trauma resulting from lawn mower, identify determinants of unfavorable final visual acuity (FVA), and assess the spectrum of microbial in posttraumatic endophthalmitis. METHODS: This retrospective study enrolled patients who experienced ocular trauma due to lawn mower at Zhongshan Ophthalmic Center from January 2013 to August 2021. Demographics, clinical features, isolated microorganisms, risk factors influencing reduced visual acuity, treatment regimens, and utilization of eyewear were collected. RESULTS: The study included 140 participants (140 eyes) (49.47 ± 12.03 years, 95% male). The predominant injury manifestations were penetrating globe injuries (75.7%) and intraocular foreign bodies (51.4%). Endophthalmitis occurred in 35 cases (25%) and Bacillus cereus (23.5%) was the primary pathogen, followed by Staphylococcus epidermidis (11.8%) and Streptococcus species (11.8%). Following the initial assessment, where 77.9% of patients had initial visual acuity (IVA) at grade IV (ranging from light perception to 4/200) and only 0.7% attained grade I (better than 20/40), post-treatment results revealed that 5.7% achieved FVA at grade I, with a concurrent decrease in patients with grade IV vision to 64.3%. Multivariate logistic regression revealed that injury protection (p < 0.001, OR = 0.237, 95% CI = 0.126-0.446), IVA (p = 0.001, OR = 4.102, 95% CI = 1.730-9.729), and retinal detachment (p = 0.042, OR = 8.105, 95% CI = 1.075-61.111) were significant independent risk factors impacting FVA. CONCLUSION: Lawn mower often cause severe ocular injuries, with high-velocity metal foreign bodies that can lead to infections, most commonly caused by Bacillus cereus. Correct use of protective gear, initial vision assessment, and detecting retinal detachment are crucial for visual prognosis.

The transmembrane channel-like 6 (TMC6) in primary sensory neurons involving thermal sensation via modulating M channels.

Introduction: The transmembrane channel-like (TMC) protein family contains eight members, TMC1-TMC8. Among these members, only TMC1 and TMC2 have been intensively studied. They are expressed in cochlear hair cells and are crucial for auditory sensations. TMC6 and TMC8 contribute to epidermodysplasia verruciformis, and predispose individuals to human papilloma virus. However, the impact of TMC on peripheral sensation pain has not been previously investigated. Methods: RNAscope was employed to detect the distribution of TMC6 mRNA in DRG neurons. Electrophysiological recordings were conducted to investigate the effects of TMC6 on neuronal characteristics and M channel activity. Zn2+ indicators were utilized to detect the zinc concentration in DRG tissues and dissociated neurons. A series of behavioural tests were performed to assess thermal and mechanical sensation in mice under both physiological and pathological conditions. Results and Discussion: We demonstrated that TMC6 is mainly expressed in small and medium dorsal root ganglion (DRG) neurons and is involved in peripheral heat nociception. Deletion of TMC6 in DRG neurons hyperpolarizes the resting membrane potential and inhibits neuronal excitability. Additionally, the function of the M channel is enhanced in TMC6 deletion DRG neurons owing to the increased quantity of free zinc in neurons. Indeed, heat and mechanical hyperalgesia in chronic pain are alleviated in TMC6 knockout mice, particularly in the case of heat hyperalgesia. This suggests that TMC6 in the small and medium DRG neurons may be a potential target for chronic pain treatment.

Effects of Gadolinium Retention in the Brains of Type 2 Diabetic Rats after Repeated Administration of Gadolinium-Based MRI Contrast Agents on Neurobiology and NLRP3 Inflammasome Activation.

BACKGROUND: The neurotoxic potential of gadolinium (Gd)-based contrast agents (GBCAs) retention in the brains of patients with type 2 diabetes mellitus (T2DM) is unclear. PURPOSE: To determine the deposition and clearance of GBCAs in T2DM rats and the mechanism by which Gd enhances nucleotide-binding oligomerization domain-3 (NLRP3) inflammasome activation. STUDY TYPE: Cross-sectional, prospective. ANIMAL MODEL: 104 T2DM male Wistar rats. FIELD STRENGTH/SEQUENCE: 9.4-T, T1-weighted fast spin echo sequence. ASSESSMENT: T2DM (male Wistar rats, n = 52) and control group (healthy, male Wistar rats, n = 52) rats received saline, gadodiamide, Gd-diethylenetriaminepentaacetic acid, and gadoterate meglumine for four consecutive days per week for 7 weeks. The distribution and clearance of Gd in the certain brain were assessed by MRI (T1 signal intensity and relaxation rate R1, on the last day of each week), inductively coupled plasma mass-spectroscopy, ultraperformance liquid chromatography mass spectrometry, and transmission electron microscopy. Behavioral tests, histopathological features, and the effects of GBCAs on neuroinflammation were also analyzed. STATISTICAL TESTS: One-way analysis of variance, bonferroni method, and unpaired t-test. A P-value <0.05 was considered statistically significant. RESULTS: The movement distance and appearance time in the open field test of the T2DM rats in the gadodiamide group were significantly shorter than in the other groups. Furthermore, the expression of NLRP3, Pro-Caspase-1, interleukin-1ß (IL-1ß), and apoptosis-associated speck-like protein containing a CARD protein in neurons was significantly higher in the gadodiamide group than in the saline group, as shown by Western blot. Gadodiamide also induced differentiation of microglia into M1 type, decreased the neuronal mitochondrial membrane potential, and significantly increased neuronal apoptosis from flow cytometry. DATA CONCLUSION: T2DM may affect both the deposition and clearance of GBCAs in the brain. Informed by the T2DM model, gadodiamide could mediate the neuroinflammatory response by NLRP3 inflammasome activation. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 1.

Hydrocarbon adsorption mechanism of modern automobile engines and methods of reducing hydrocarbon emissions during cold start process: A review.

With the global emphasis on environmental protection and increasingly stringent emission regulations for internal combustion engines, there is an urgent need to overcome the problem of large hydrocarbon (HC) emissions caused by unstable engine cold starts. Synergistic engine pre-treatment (reducing hydrocarbon production) as well as after-treatment devices (adsorbing and oxidizing hydrocarbons) is the fundamental solution to emissions. In this paper, the improvement of hydrocarbon emissions is summarized from two aspects: pre-treatment and after-treatment. The pre-treatment for engine cold start mainly focuses on summarizing the intake control, fuel, and engine timing parameters. The after-treatment mainly focuses on summarizing different types of adsorbents and modifications (mainly including different molecular sieve structures and sizes, preparation conditions, silicon aluminum ratio, ion exchange modification, and heterogeneity, etc.), adsorptive catalysts (mainly including optimization of catalytic performance and structure), and catalytic devices (mainly including coupling with thermal management equipment and HC trap devices). In this paper, a SWOT (strength, weakness, opportunity, and threat) analysis of pre-treatment and after-treatment measures is conducted. Researchers can obtain relevant research results and seek new research directions and approaches for controlling cold start HC emissions.

All who wander are not lost: the search for homology during homologous recombination.

Homologous recombination (HR) is a template-based DNA double-strand break repair pathway that functions to maintain genomic integrity. A vital component of the HR reaction is the identification of template DNA to be used during repair. This occurs through a mechanism known as the homology search. The homology search occurs in two steps: a collision step in which two pieces of DNA are forced to collide and a selection step that results in homologous pairing between matching DNA sequences. Selection of a homologous template is facilitated by recombinases of the RecA/Rad51 family of proteins in cooperation with helicases, translocases, and topoisomerases that determine the overall fidelity of the match. This menagerie of molecular machines acts to regulate critical intermediates during the homology search. These intermediates include recombinase filaments that probe for short stretches of homology and early strand invasion intermediates in the form of displacement loops (D-loops) that stabilize paired DNA. Here, we will discuss recent advances in understanding how these specific intermediates are regulated on the molecular level during the HR reaction. We will also discuss how the stability of these intermediates influences the ultimate outcomes of the HR reaction. Finally, we will discuss recent physiological models developed to explain how the homology search protects the genome.

Stoichiometry-Tunable Synthesis and Magnetic Property Exploration of Two-Dimensional Chromium Selenides.

Emerging 2D chromium-based dichalcogenides (CrXn (X = S, Se, Te; 0 < n ≤ 2)) have provoked enormous interests due to their abundant structures, intriguing electronic and magnetic properties, excellent environmental stability, and great application potentials in next generation electronics and spintronics devices. Achieving stoichiometry-controlled synthesis of 2D CrXn is of paramount significance for such envisioned investigations. Herein, we report the stoichiometry-controlled syntheses of 2D chromium selenide (CrxSey) materials (rhombohedral Cr2Se3 and monoclinic Cr3Se4) via a Cr-self-intercalation route by designing two typical chemical vapor deposition (CVD) strategies. We have also clarified the different growth mechanisms, distinct chemical compositions, and crystal structures of the two type materials. Intriguingly, we reveal that the ultrathin Cr2Se3 nanosheets exhibit a metallic feature, while the Cr3Se4 nanosheets present a transition from p-type semiconductor to metal upon increasing the flake thickness. Moreover, we have also uncovered the ferromagnetic properties of 2D Cr2Se3 and Cr3Se4 below ∼70 K and ∼270 K, respectively. Briefly, this research should promote the stoichiometric-ratio controllable syntheses of 2D magnetic materials, and the property explorations toward next generation spintronics and magneto-optoelectronics related applications.

Phase and Composition Engineering of Self-Intercalated 2D Metallic Tantalum Sulfide for Second-Harmonic Generation.

Self-intercalation in two-dimensional (2D) materials is significant, as it offers a versatile approach to modify material properties, enabling the creation of interesting functional materials, which is essential in advancing applications across various fields. Here, we define ic-2D materials as covalently bonded compounds that result from the self-intercalation of a metal into layered 2D compounds. However, precisely growing ic-2D materials with controllable phases and self-intercalation concentrations to fully exploit the applications in the ic-2D family remains a great challenge. Herein, we demonstrated the controlled synthesis of self-intercalated H-phase and T-phase Ta1+xS2 via a temperature-driven chemical vapor deposition (CVD) approach with a viable intercalation concentration spanning from 10% to 58%. Atomic-resolution scanning transmission electron microscopy-annular dark field imaging demonstrated that the self-intercalated Ta atoms occupy the octahedral vacancies located at the van der Waals gap. The nonperiodic Ta atoms break the centrosymmetry structure and Fermi surface properties of intrinsic TaS2. Therefore, ic-2D T-phase Ta1+xS2 consistently exhibit a spontaneous nonlinear optical (NLO) effect regardless of the sample thickness and self-intercalation concentrations. Our results propose an approach to activate the NLO response of centrosymmetric 2D materials, achieving the modulation of a wide range of optoelectronic properties via nonperiodic self-intercalation in the ic-2D family.

An attention-based approach for assessing the effectiveness of emotion-evoking in immersive environment.

Visual stimuli within an immersive virtual environment impact human perception and behavior in notably different ways compared to the real world. Previous studies have presented evidence indicating that individuals in various emotional states exhibit an unconscious attentional bias toward either positive or negative stimuli. However, whether these findings can be replicated within an immersive virtual environment remains uncertain. In this study, we devised an attention-based experiment to explore whether the correlation between participants' emotional states and the valence of visual stimuli influences their attentional bias. Participants (n=28) viewed 360-degree videos with varying valence levels (positive and negative) to evoke emotions. Subsequently, we utilized standard emotional human faces as stimuli to assess how the consistency in video valence and emotional faces affects reaction time (RT) in Go tasks and error rates in No-go tasks. We employed the Ex-Gaussian approach to analyze the RT data. The parameters-mu (µ), sigma (σ), and tau (τ)-were computed to denote response speed and attentional lapses, respectively. Our findings revealed a significant increase in tau (τ) when the valence of the video and emotional faces aligned. This suggests that the Go/No-go paradigm is effective in evaluating the impact of emotion-evoking stimuli within an immersive environment.

Tunable Adhesion for All-Dry Transfer of 2D Materials Enabled by the Freezing of Transfer Medium.

The real applications of chemical vapor deposition (CVD)-grown graphene films require the reliable techniques for transferring graphene from growth substrates onto application-specific substrates. The transfer approaches that avoid the use of organic solvents, etchants, and strong bases are compatible with industrial batch processing, in which graphene transfer should be conducted by dry exfoliation and lamination. However, all-dry transfer of graphene remains unachievable owing to the difficulty in precisely controlling interfacial adhesion to enable the crack- and contamination-free transfer. Herein, through controllable crosslinking of transfer medium polymer, the adhesion is successfully tuned between the polymer and graphene for all-dry transfer of graphene wafers. Stronger adhesion enables crack-free peeling of the graphene from growth substrates, while reduced adhesion facilitates the exfoliation of polymer from graphene surface leaving an ultraclean surface. This work provides an industrially compatible approach for transferring 2D materials, key for their future applications, and offers a route for tuning the interfacial adhesion that would allow for the transfer-enabled fabrication of van der Waals heterostructures.

Exploring the potential mechanism of Heng-Gu-Gu-Shang-Yu-He-Ji therapy for osteoporosis based on network pharmacology and transcriptomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Heng-Gu-Gu-Shang-Yu-He-Ji (Osteoking, OK) is a well-known formula for fracture therapy. In clinic, OK is effective in treating fractures while alleviating osteoporosis (OP) symptoms. However, active components of OK and the associated molecular mechanisms remain not fully elucidated. AIM OF THE STUDY: This study aims to systematically evaluate the anti-osteoporosis efficacy of OK and for the first time combine network pharmacology with high-throughput whole gene transcriptome sequencing to study its underlying mechanism. MATERIALS AND METHODS: In this study, the osteoporosis model was established by the castration of both ovaries. The level of serum bone turnover factor was detected by enzyme-linked immunosorbent assay. Micro-CT and HE staining were used to observe the changes of bone histopathology, and nano-indentation technique was used to detect the biomechanical properties of rat bone. The main active Chemical components of OK were identified using UPLC-DAD. Efficacy verification and mechanism exploration were conducted by network pharmacology, molecular docking, whole gene transcriptomics and in vivo experiments. RESULTS: In our study, OK significantly improved bone microarchitecture and bone biomechanical parameters in OVX rats, reduced osteoclast indexes such as C-telopeptide of type I collage (CTX-I) and increased Osteoprotegerin (OPG)/Receptor activator of NF-κB ligand (RANKL) levels. Mechanistically, PI3K/AKT pathway was a common pathway for genome enrichment analysis (KEGG) of both network pharmacology and RNA-seq studies. G protein-ß-like protein (GßL), Ribosomal-protein S6 kinase homolog 2 (S6K2), and Phosphoinositide 3-kinase (PI3K) appeared differentially expression in the PI3K-AKT signaling pathway. These results were also confirmed by qRT-PCR and immunohistochemistry. CONCLUSIONS: OK may be used to treat osteoporosis, at least partly by activating PI3K/AKT/mTORC1 signaling pathway.

Association of RPS26 gene polymorphism with different types of diabetes in Chinese individuals.

AIMS/INTRODUCTION: Different types of diabetes show distinct genetic characteristics, but the specific genetic susceptibility factors remain unclear. Our study aimed to explore the associations between the ribosomal protein S26 (RPS26) gene rs1131017 polymorphisms and susceptibility to type 1 diabetes mellitus, latent autoimmune diabetes in adults (LADA) and type 2 diabetes mellitus in the Chinese Han population, and their correlations with clinical features. MATERIALS AND METHODS: Genotyping of the rs1131017 variant was carried out for 1,006 type 1 diabetes mellitus patients, 210 LADA patients, 642 type 2 diabetes mellitus patients and 2,099 control individuals. RESULTS: We found that the rs1131017 C allele was a risk locus for both type 1 diabetes mellitus and LADA (odds ratio [OR] 1.50, 95% confidence interval [CI] 1.33-1.69, P < 0.001; OR 1.31, 95% CI 1.04-1.64, P = 0.021, respectively). Nevertheless, this association was not found for type 2 diabetes mellitus. Carrying the C allele genotype was associated with a lower postprandial C-peptide for type 1 diabetes mellitus (OR 1.41, 95% CI 1.11-1.80, P = 0.006) and lower fasting C-peptide for LADA (OR 1.55, 95% CI 1.01-2.38, P = 0.047). Interestingly, a lower GC frequency was noted for LADA than for type 1 diabetes mellitus, regardless of classification based on age at diagnosis, C-peptide or glutamic acid decarboxylase antibody positivity. CONCLUSIONS: The RPS26 polymorphism was associated with susceptibility and clinical characteristics of type 1 diabetes mellitus and LADA in the Chinese population, but was not related to type 2 diabetes mellitus. Thus, it might serve as a novel biomarker for particular types of diabetes.

Hepatocyte nuclear factor 1B deletion, but not intragenic mutation, might be more susceptible to hypomagnesemia.

AIMS: HNF1B syndrome is caused by defects in the hepatocyte nuclear factor 1B (HNF1B) gene, which leads to maturity-onset diabetes of the young type 5 and congenital organ malformations. This study aimed to identify a gene defect in a patient presenting with diabetes and severe diarrhea, while also analyzing the prevalence of hypomagnesemia and its correlation with the HNF1B genotype. MATERIALS AND METHODS: Whole exome sequencing was used to identify responsible point mutations and small indels in the proband and their family members. Multiplex ligation-dependent probe amplification was carried out to identify HNF1B deletions. Furthermore, an analysis of published data on 539 cumulative HNF1B cases, from 29 literature sources, was carried out to determine the correlation between the HNF1B genotype and the phenotype of serum magnesium status. RESULTS: Using multiplex ligation-dependent probe amplification, we identified a de novo heterozygous HNF1B deletion in the patient, who showed dorsal pancreas agenesis and multiple kidney cysts, as detected by magnetic resonance imaging. Magnesium supplementation effectively alleviated the symptoms of diarrhea. Hypomagnesemia was highly prevalent in 192 out of 354 (54.2%) patients with HNF1B syndrome. Compared with patients with intragenic mutations, those with HNF1B deletions were more likely to suffer from hypomagnesemia, with an odds ratio of 3.1 (95% confidence interval 1.8-5.4). CONCLUSIONS: Hypomagnesemia is highly prevalent in individuals with HNF1B syndrome, and those with HNF1B deletion are more susceptible to developing hypomagnesemia compared with those with intragenic mutations. The genotype-phenotype associations in HNF1B syndrome have significant implications for endocrinologists in terms of genotype detection, treatment decisions and prognosis assessment.

The effect of perceived stress on social isolation in young and middle-aged maintenance haemodialysis patients: A polynomial regression and response surface analysis.

Patients on maintenance haemodialysis (MHD) face social isolation due to the far-reaching effects of their disease and treatment. Based on the Transactional Model of Stress and Coping, we analysed the relationship between perceived stress and social isolation in patients, and the mediating role of internal health-related locus of control (IHLC) from the perspective of co-existence of perceived helplessness (HEL) and perceived self-efficacy (SEL). We used structured questionnaires to investigate 332 cases of young and middle-aged MHD patients in four tertiary hospitals in Guangdong, China. Polynomial regression and response surface analysis were conducted, along with tests of mediating effects on the data. The research was based on STROBE guidelines. The results showed that perceived stress is significantly and positively associated with social isolation. When the HEL and SEL of perceived stress were congruent, the joint effect of the two was in a positive curvilinear relationship to social isolation, when the two were incongruent, the risk of social isolation was lower for "low HEL-high SEL" patients compared to the "high HEL-low SEL" combination. The more congruent in HEL -SEL, the lower the risk of social isolation for the patients, with the IHLC playing a mediating role in this association. This study reveals that the coexistence of perceived stress's HEL and SEL affects social isolation through congruent and incongruent matching mechanism, providing additional explanations for the mechanism of occurrence of patients' social isolation.