Diverse functions of Tribbles homolog 3 in cancers and its potential as a therapeutic target.

Currently, cancer is the second leading cause of death worldwide, and potential targeted drugs and molecular pathways for cancer development and progression have been a hot research topic worldwide. In recent years, the importance of the kinase superfamily in diseases has been well demonstrated by studies on various molecular mechanisms of kinases and the successful application of their inhibitors in diseases. Pseudokinases are members of the kinase superfamily, which have been increasingly documented to play a crucial role in cancers year after year. As a member of pseudokinases, tribbles homolog 3 (TRIB3) also exerts diverse functions in different cancers through different interacting proteins and molecular pathways, especially in tumor immunity, stemness, drug resistance, metabolism, and autophagy. In addition, peptide drugs targeting TRIB3 have high specificity in preclinical studies, which shows great promise for TRIB3 application in diseases including cancers. In this review, we dissect diverse functions played by TRIB3 in different cancers, describing the underlying mechanisms in detail. Notably, inhibitors and agonists currently available for TRIB3 are discussed, indicating the potential for TRIB3 as a therapeutic target.

Adiposity indicators exhibit depot- and sex-specific associations with multimorbidity onset: A cohort study of the UK Biobank.

AIM: This study investigated the depot- and sex-specific associations of adiposity indicators with incident multimorbidity and comorbidity pairs. MATERIALS AND METHODS: We selected 382 678 adults without multimorbidity (≥2 chronic diseases) at baseline from the UK Biobank. General obesity, abdominal obesity and body fat percentage indices were measured. RESULTS: Cox proportional hazard regression analyses of general obesity indices revealed that for every one-unit increase in body mass index, the risk of incident multimorbidity increased by 5.2% (95% confidence interval 5.0%-5.4%). A dose-response relationship was observed between general obesity degrees and incident multimorbidity. The analysis of abdominal obesity indices showed that for every 0.1 increment in waist-to-height ratio and waist-to-hip ratio, the risk of incident multimorbidity increased by 42.0% (37.9%-46.2%) and 27.9% (25.7%-30.0%), respectively. Central obesity, as defined by waist circumference, contributed to a 23.2% increased risk of incident multimorbidity. Hip circumference and hip-to-height ratio had protective effects on multimorbidity onset. Consistent findings were observed for males and females. Body fat percentage elevated 3% (0.2%-5.9%) and 5.3% (1.1%-9.7%) risks of incident multimorbidity in all adults and females, respectively. Arm fat percentages elevated 5.3% (0.8%-9.9%) and 19.4% (11.0%-28.5%) risks of incident multimorbidity in all adults and males, respectively. The general obesity indices, waist circumference, waist-to-height ratio, waist-to-hip ratio and central obesity increased the onset of comorbidity pairs, whereas hip circumference and hip-to-height ratio decreased the onset of comorbidity pairs. These adiposity indicators mainly affect diabetes mellitus-related comorbidity onset in males and hypertensive-related comorbidity onset in females. CONCLUSIONS: Adiposity indicators are predictors of multimorbidity and comorbidity pairs and represent a promising approach for intervention.

Examining the Effects of PrEP Use on Sexual Behaviors and Sexually Transmitted Infections Among Chinese Men who have Sex with Men: A Cross-Sectional Study.

Men who have sex with men (MSM) is a high-risk population for HIV and sexually transmitted infections (STIs). Pre-exposure prophylaxis (PrEP) is effective in HIV prevention. This study aims to examine the differences in sexual behaviors, STI prevalence and HIV/STI testing across subgroups of MSM with various PrEP use. Data were collected via a cross-sectional survey in an MSM community in Xi'an, Shaanxi, from 2022.01 to 2022.09. Participants were categorized as 'PrEP-naïve and unwilling to use', 'PrEP-naïve but willing to use', and 'current or former PrEP users'. Shannon index was used to assess sexual act diversity and multivariate logistic regression analyzed factors associated with PrEP use. Of the 1,131 MSM participants, 23.52% were PrEP-naïve and unwilling, 64.98% were PrEP-naïve but willing, and 11.49% were current or former PrEP users. The PrEP-naïve but willing group had the highest recent STI testing rates at 73.06% and showed greater sexual act diversity (Shannon index 1.61). This group also had the highest syphilis rates (7.49% vs. 6.47% and2.54%, p < 0.01). Younger age (18-30: OR = 0.39 (0.18-0.85); 31-40: OR = 0.43 (0.20-0.96)) and lower education (high school/vocational: OR = 0.15 (0.04-0.58); associate degree: OR = 0.21 (0.06-0.71)) were factors that negatively influenced PrEP use. Current or former PrEP users had the highest oropharyngeal gonorrhea (14.39% vs. 9.68% and 5.80%, p < 0.01) and overall gonorrhea rates (20.86% vs. 17.17% and 8.37%, p < 0.001). 'PrEP-naïve but willing' participants consistently demonstrated high-risk sexual behavior, increased STI testing, and more diverse sexual acts, whereas PrEP users had the highest STI prevalence.

Comparison of clinical outcome after implantation of two toric intraocular lenses with different haptic type: a prospective randomized controlled trial.

OBJECTIVE: To study the effect of astigmatism correction, rotational stability, and related factors of two different haptic type toric intraocular lenses. METHODS: A prospective, randomized, controlled trial. Cataract patients with preoperative corneal astigmatism of > 1 D were randomly implanted with C-loop haptic toric IOL (AcrySof-toric IOL) (group A) or plate-haptic toric IOL (AT TORBI 709 M IOL) (group B). The residual astigmatism, intraocular lens rotation, and visual quality were determined and compared between the two groups at 3 months after surgery. RESULTS: Seventy-nine eyes were included in this study, including 40 eyes in the group A and 39 eyes in the group B. No significant difference in preoperative visual acuity, intraocular pressure, and ophthalmic biological parameters was found between the two groups. There was no significant difference in residual astigmatism between the two groups at 3 months after surgery (P > 0.05). The rotation degree in the group A was 3.85 ± 2.92°, the rotation degree in the group B was 2.33 ± 2.31°, and a significant difference in intraocular lens rotation was identified between the two groups (P < 0.05). Upon exploring the rotation-related factors of the two different haptic type toric intraocular lenses, the rotation after implanting C-loop haptic toric IOL was positively correlated with axial length (Pearson r = 0.522, P = 0.01) and corneal white-to-white distance (Pearson correlation analysis r = 0.356, P = 0.024). CONCLUSIONS: The two different haptic type toric intraocular lenses effectively corrected regular corneal astigmatism and provided a good rotational stability after surgery. But the stability of plate-haptic toric IOL was better than that of C-loop haptic toric IOL. The rotational stability of C-loop haptic toric IOL was often related to axial length and corneal white-to-white distance.

Acoustic Waves Induced by Einstein-de Haas Effect in the Ultrafast Core Reversal of Magnetic Vortex.

The interaction between acoustic wave and magnetization in ferromagnetic thin films has attracted great attention due to its interesting physics and potential applications. However, up to now, the magneto-acoustic interaction has mainly been studied on the basis of magnetostriction. In this Letter, we develop a phase field model of magneto-acoustic interaction based on the Einstein-de Haas effect, and predict the acoustic wave during the ultrafast core reversal of magnetic vortex in a ferromagnetic disk. Because of the Einstein-de Haas effect, the ultrafast change of magnetization at the vortex core leads to a large mechanical angular momentum, which induces a body couple at the vortex core and excites a high-frequency acoustic wave. Moreover, the displacement amplitude of the acoustic wave is highly dependent on the gyromagnetic ratio. The smaller the gyromagnetic ratio is, the larger the displacement amplitude is. The present work not only provides a new mechanism for dynamic magnetoelastic coupling but also sheds new insights on the magneto-acoustic interaction.

Visual performance and rotational stability of a multifocal toric intraocular lens in myopic eyes.

OBJECTIVE: This study aimed to evaluate the visual performance and rotational stability of the multifocal toric intraocular lens in myopes. METHODS: This prospective, observational study included patients with an axial length of ≥24.5 mm and regular corneal astigmatism of >1 diopter who underwent phacoemulsification cataract surgery and implantation of a multifocal toric intraocular lens (AT LISA toric 909M). The visual acuity, defocus curves, residual astigmatism, rotational stability, higher-order aberrations (HOAs), modulation transfer function (MTF), spectacle dependence and patient satisfaction were evaluated 3 months after surgery. RESULTS: Forty-three eyes from 30 patients were enrolled in this study. Postoperatively, uncorrected distance and near visual acuities (logMAR) were 0.09 ± 0.08 (standard deviation, SD) and 0.14 ± 0.08, respectively. The defocus curve analysis provided a bimodal curve showing two peaks of maximum vision at 0.0 D and at -3.0 D defocus level. The multifocal toric intraocular lens showed excellent rotational stability; the mean rotation was 4.02 ± 2.49 (SD) degrees at 3 months postoperatively. Refractive predictability was excellent with a mean spherical equivalent of 0.19 ± 0.37 (SD) diopters (D) and a mean refractive cylinder of -0.34 ± 0.39 (SD) D. CONCLUSIONS: The diffractive multifocal toric intraocular lens, AT LISA toric 909M, provided effective distance and near visual acuities in myopic eyes. It was a predictable and effective device with good rotational stability for the correction of preexisting astigmatism during cataract surgery. In this study, more than 80% of patients achieved spectacle independence.

Incidence and Risk Factors of Repositioning Surgery to Correct Misalignment of Toric Intraocular Lenses After Cataract Surgery：A Single-Center Retrospective Observational Study.

PURPOSE: To analyze the incidence and outcomes of repositioning surgery to correct misalignment of several toric intraocular lenses (IOLs) after cataract surgery. METHODS: In this retrospective study, patients who underwent repositioning surgery to correct misalignment of toric IOLs following cataract surgery between January 2019 and December 2021 were enrolled. The medical data on patients' age, gender, preoperative axial length, corneal astigmatism, the axis of astigmatism, IOL models, IOL axis, uncorrected distance visual acuity, residual refraction, and postoperative outcomes were analyzed. RESULTS: Among the 1135 eyes implanted with toric IOLs at Qingdao Eye Hospital, 23 (2.026%, 23/1135) underwent repositioning surgery. Univariate analysis revealed that the incidence of repositioning surgery was significantly lower with AcrySof (0.636%, 5/786) than with ZEISS (2.959%, 5/169) and TECNIS (7.222%, 13/180) IOL platforms; The incidence of repositioning surgery with monofocal toric IOLs (1.169%, 11/941) was significantly lower than multifocal toric IOLs (6.186%, 12/194) (P<0.001); Additionally, a significant difference in age was also observed (P=0.002). Multivariate logistic regression analysis showed that IOL platform (P=0.004) and younger age (P=0.006) were independent risk factors for repositioning surgery. CONCLUSION: The incidence of repositioning surgery of toric IOLs after cataract surgery was 2.026%. It was linked to the IOL platform, multifocal toric IOLs, and younger age.

Macular toxicity of low-concentration cefuroxime during cataract surgery in vitrectomized eyes.

OBJECTIVE: The objective of this study was to determine the toxic effect and clinical characteristics of 1 mg/ml cefuroxime sodium on retinas after phacoemulsification in vitrectomized eyes. METHODS: Cataract patients with vitrectomized eyes were studied retrospectively. Phacoemulsification combined with intraocular lens implantation was performed uneventfully. Best Corrected Visual Acuity（BCVA）, intraocular pressure（IOP）, fundus photography, macular central thickness, and angiography were collected and analyzed. They were studied in patients with macular edema to evaluate macular toxicity. RESULTS: 92 cases (92 eyes) were enrolled, including 44 eyes of males and 48 eyes of females with an average age of 55.35 ± 12.32 years. Univariate analysis showed that the intraoperative use of balanced salt solution (BSS) containing 1 mg/ml cefuroxime sodium compound electrolyte and macular involvement in primary vitrectomy were important risk factors for macular edema on the first day after cataract surgery (P < 0.05). In addition, the characteristics of this kind of macular edema were studied; the thickness of macular fovea was significantly high at 1-day follow-up (P < 0.05), but there was no difference between pre-operation and 1-week post-operation (P > 0.05). CONCLUSION: Low-concentration cefuroxime sodium can cause acute macular edema in vitrectomized eyes, which can heal within one week after surgery.

Enhanced nitrogen removal upon the addition of volatile fatty acids from activated sludge by combining calcium peroxide and low-thermal pretreatments.

This study investigated a combined low-thermal and CaO2 pretreatment to enhance the volatile fatty acid (VFA) production from waste activated sludge (WAS). The fermentative product was added to a sequencing batch reactor (SBR) as an external carbon source to enhance nitrogen removal. The results showed that the combined pretreatment improved WAS solubilization, releasing more biodegradable substrates, such as proteins and polysaccharides, from TB-EPS to LB-EPS and S-EPS. The maximum VFA production of 3529 ± 188 mg COD/L was obtained in the combined pretreatment (0.2 g CaO2/g VS + 70 °C for 60 min), which was 2.1 and 1.4-fold of that obtained from the sole low-thermal pretreatment and the control test, respectively. Consequently, when the fermentative liquid was added as an external denitrification carbon source, the effluent total nitrogen decreased to Class A of the discharge standard for pollutants in rural wastewater treatment plants in most areas of China.

IOP-induced regional displacements in the optic nerve head and correlation with peripapillary sclera thickness.

Mechanical insult induced by intraocular pressure (IOP) is likely a driving force in the disease process of glaucoma. This study aimed to evaluate regional displacements in human optic nerve head (ONH) and peripapillary tissue (PPT) in response to acute IOP elevations, and their correlations with morphological characteristics of the posterior eye. Cross-sectional (2D) images of the ONH and PPT in 14 globes of 14 human donors were acquired with high-frequency ultrasound during whole globe inflation from 5 to 30 mm Hg. High-frequency ultrasound has a spatial resolution of tens of micrometers and is capable of imaging through the ONH and PPT thickness. Tissue displacements were calculated using a correlation-based speckle tracking algorithm for a dense matrix of kernels covering the 2D imaging plane. The ONH was manually segmented in the ultrasound B-mode images acquired at 5 mmHg based on echogenicity. The lamina cribrosa (LC) boundaries were visible in eight of the fourteen eyes and the LC region was segmented using a semi-automated superpixel-based method. The ONH had larger radial displacement than the PPT in all tested eyes and the difference increased with increasing IOP. A significant negative correlation was found between ONH-PPT displacement difference and PPT thickness (p < 0.05), while no significant correlations were found between ONH-PPT displacement difference and other morphological parameters including PPT radius of curvature, scleral canal size, LC thickness and anterior LC surface depth. Within the ONH, the radial displacement decreased in the region anterior to and across LC but not in the region posterior to LC. Finite element models using simplified geometry and material properties confirmed the role of LC in reducing the overall ONH radial displacements, but did not predict the displacement gradient change observed experimentally. These results suggested that a thinner PPT may be associated with a larger relative posterior motion of the ONH with respect to the surrounding PPT and the LC may play a major role in preventing excessive posterior displacement of ONH during acute IOP elevations.

Municipal wastewater treatment plants coupled with electrochemical, biological and bio-electrochemical technologies: Opportunities and challenge toward energy self-sufficiency.

Municipal wastewater treatment plants (WWTPs) will face challenges in the coming decades including reducing energy consumption and decreasing carbon emissions. These challenges can be addressed by combining electrochemical, biological, and bio-electrochemical technologies within existing WWTPs. The results from this review indicate that electrochemical technology is an effective advanced treatment method for WWTPs. However, electrochemical technology is not yet economically suitable as a stand-alone unit for treating wastewater because it consumes energy in the operation process. Electricity generation from biological and bio-electrochemical technologies can provide the power supply needed for WWTP electrochemical processes while reducing greenhouse gas emissions. WWTPs coupled with electrochemical, biological, and bio-electrochemical technologies can increase electricity recovery in WWTPs, impart energy self-sufficiency to the WWTPs, and decrease greenhouse gas emissions.

Chitinophaga caeni sp. nov., isolated from activated sludge.

A novel Gram-stain-negative, non-motile, non-spore-forming, rod-shaped, strictly aerobic bacterium, designated strain 13T, was isolated from an activated sludge wastewater treatment plant in Beijing, China. 16S rRNA gene sequence analysis placed this organism within the genus Chitinophaga of the class Bacteroidetes, with Chitinophaga skermanii CC-SG1B (92.4 % gene sequence similarity) and Chitinophaga rupis CS5-B1 (91.2 %) as its closest relatives. This isolate contained meso-diaminopimelic acid as the diagnostic diamino acid and the whole-cell hydrolysate was ribose. Phosphatidylethanolamine was the predominant polar lipid. The major cellular fatty acids were iso-C15 : 0, C16 : 1ω5c and iso-C17 : 0 3-OH. Menaquinone-7 was the only isoprenoid quinone present. The complete genome of the novel strain was sequenced; the size of the genome was 5.28 Mb and the genomic DNA G+C content was 42.5 mol%. The phenotypic, chemotaxonomic and phylogenetic data showed that strain 13T represents a novel species of the genus Chitinophaga, for which the name Chitinophaga caeni sp. nov. is proposed. The type strain is 13T (=CICC 24262T=KCTC 62265T).

COPS5 inhibition arrests the proliferation and growth of serous ovarian cancer cells via the elevation of p27 level.

The fifth component of the COP9 signalosome complex (COPS5), which plays an essential role in ubiquitin-mediated protein degradation, has been found as a prognostic biomarker for multiple cancers, however, the role of COPS5 in serous ovarian cancer (SOC) remain to be clarified. In this study, we found that COPS5 expression was significantly increased in SOC cells and tissues compared with those controls. Mechanistically, COPS5 and p27was proved to interact with each other, with COPS5 acts as a negative regulator of p27. SOC cells with COPS5 depletion were arrested in G1/G0-phase and exhibited a reduced proliferation ability and an increased cytoplasmic p27 expression. Whereas, the cells were stuck at S-phase accompanied with an elevation of nucleus p27 expression after knocking down COPS6 or blocking COPS5 by CSN5i-3. Furthermore, inhibition of COPS5 resulted in an elevation of Akt expression and sensitized SOC cells to Akt inhibitor MK2206. Suppression of COPS5 and Akt offers a potential strategy for the treatment of SOC.

Incentivizing Verifiable Privacy-Protection Mechanisms for Offline Crowdsensing Applications.

Incentive mechanisms of crowdsensing have recently been intensively explored. Most of these mechanisms mainly focus on the standard economical goals like truthfulness and utility maximization. However, enormous privacy and security challenges need to be faced directly in real-life environments, such as cost privacies. In this paper, we investigate offline verifiable privacy-protection crowdsensing issues. We firstly present a general verifiable privacy-protection incentive mechanism for the offline homogeneous and heterogeneous sensing job model. In addition, we also propose a more complex verifiable privacy-protection incentive mechanism for the offline submodular sensing job model. The two mechanisms not only explore the private protection issues of users and platform, but also ensure the verifiable correctness of payments between platform and users. Finally, we demonstrate that the two mechanisms satisfy privacy-protection, verifiable correctness of payments and the same revenue as the generic one without privacy protection. Our experiments also validate that the two mechanisms are both scalable and efficient, and applicable for mobile devices in crowdsensing applications based on auctions, where the main incentive for the user is the remuneration.

MUS81 is associated with cell proliferation and cisplatin sensitivity in serous ovarian cancer.

The dysfunction of DNA damage repair (DDR) pathway contributes to tumorigenesis and drug-resistance in cancer. MUS81 is a member of the conserved xeroderma pigmentosum group F (XPF) family protein of endonucleases, which is important to the DDR pathway. However, the role of MUS81 in the development of ovarian cancer remains uncertain. To explore the expression of MUS81 and its association to serous ovarian cancer (SOC), 43 biopsies of SOC patients were detected by qRT-PCR, and 29 specimens were further performed by immunohistochemistry analysis. Here, we observed that MUS81 was over-expressed in SOC tissues at both transcript and protein levels, and the expression level of MUS81 protein in ovarian cancer cell lines was also higher than that in human normal ovarian surface epithelial cell line (HOSEpiC). We also found that down-regulation of MUS81 expression in ovarian cancer cells inhibited cell proliferation and colony formation ability, and influenced cell cycle progression. Moreover, inhibition of MUS81 expression induced cellular senescence and enhanced the antitumor effect of cisplatin. Down-regulation of MUS81 expression could suppress the growth and development of SOC. These results indicate that MUS81 might play important roles in the progression of SOC and influence the antitumor effect of cisplatin.

ß-cell dedifferentiation in HOMA-ßlow and HOMA-ßhigh subjects.

CONTEXT: ß-cell dedifferentiation ratio is increased in type 2 diabetes; but its direct link to in vivo ß-cell function in human remains unclear. OBJECTIVE: The present study was designed to investigate whether ß-cell dedifferentiation in situ was closely associated with ß-cell function in vivo and to identify targets crucial for ß-cell dedifferentiation/function in human. METHODS: We acquired HOMA-ß values, calculated the number of hormone-negative endocrine cells and evaluated important markers and novel candidates for ß-cell dedifferentiation/function on paraneoplastic pancreatic tissues from 13 patients with benign pancreatic cystic neoplasm (PCN) or intrapancreatic accessory spleen. RESULTS: Both ß-cell dedifferentiation ratio and dedifferentiation marker (Aldh1a3) were inversely related with in vivo ß-cell function (HOMA-ß) and in situ ß-cell functional markers Glut2 and Ucn3 in human. Moreover, the islets from HOMA-ßlow subjects were manifested as 1) increased ß-cell dedifferentiation ratio, 2) enriched dedifferentiation maker Aldh1a3, and 3) lower expression of Glut2 and Ucn3, compared to those from HOMA-ßhigh subjects. We found that basic leucine zipper transcription factor 2 (Bach2) expression was significantly induced in islets from HOMA-ßlow patients and was positively correlated with the ratio of ß-cell dedifferentiation in human. CONCLUSIONS: Our findings emphasize the contribution of ß-cell dedifferentiation to ß-cell dysfunction in human. The Bach2 induction in ß-cells with higher frequency of dedifferentiation observed in HOMA-ßlow subjects reinforce its distinctive role as a pharmaceutical target of ß-cell dedifferentiation for the treatment of human diabetes.

Notch signaling and targeted therapy in non-small cell lung cancer.

The Notch signaling pathway plays pivotal roles in cell proliferation, stemness and invasion of non-small cell lung cancer (NSCLC). The human Notch family consists of four receptors, namely Notch1, Notch2, Notch3, and Notch4. These receptors are transmembrane proteins that play crucial roles in various cellular processes. Notch1 mostly acts as a pro-carcinogenic factor in NSCLC but sometimes acts as a suppressor. Notch2 has been demonstrated to inhibit the growth and progression of NSCLC, whereas Notch3 facilitates these biological behaviors of NSCLC. The role of Notch4 in NSCLC has not been fully elucidated, but it is evident that Notch4 promotes tumor progression. At present, drugs targeting the Notch pathway are being explored for NSCLC therapy, a majority of which are already in the stage of preclinical research and clinical trials, with bright prospects in the clinical treatment of NSCLC.

Strain-mediated multistate skyrmion for neuron devices.

Magnetic skyrmions are potential candidates for neuromorphic computing because of their inherent topological stability, low drive current density and nanoscale size. However, an artificial neuron device based on current-driven skyrmion motion cannot satisfy the requirement of energy efficiency and integration density due to hundreds of millions of interconnected neurons and synapses present in the deep networks. Here, we present a compact and energy efficient skyrmion-based artificial neuron consisting of ferromagnetic/heavy metal/ferroelectric layers which uses strain-mediated voltage manipulation of skyrmion states to mimic the Integrate-and-Fire (IF) function of biological neurons. By implementation of a spiking neural network (SNN) based on the proposed skyrmionic neuronal devices, it can achieve a high accuracy of 95.08% on a modified National Institute of Standards and Technology (MNIST) handwritten digit dataset, as well as a low power consumption of ∼46.8 fJ per epoch per neuron. The present work suggests a novel way to realize energy-efficient and high-density neuromorphic computing.

Association Between Geriatric Nutrition Risk Index and 90-Day Mortality in Older Adults with Chronic Obstructive Pulmonary Disease: a Retrospective Cohort Study.

Background: Malnutrition adversely affects prognosis in various medical conditions, but its implications in older adults with Chronic Obstructive Pulmonary Disease (COPD) in the ICU are underexplored. The geriatric nutritional risk index (GNRI) is a novel tool for assessing malnutrition risk. This study investigates the association between GNRI and 90-day mortality in this population. Methods: We selected older adults with COPD admitted to the ICU from Medical Information Mart for Intensive Care (MIMIC)-IV 2.2 database. A total of 666 patients were categorized into four groups based on their GNRI score: normal nutrition (>98), mild malnutrition (92-98), moderate malnutrition (82-91), and severe malnutrition (≤81) groups. We employed a restricted cubic spline (RCS) analysis to assess the presence of a curved relationship between them and to investigate any potential threshold saturation effect. Results: In multivariate Cox regression analyses, compared with individuals had normal nutrition (GNRI in Q4 >98), the adjusted HR values for GNRI in Q3 (92-98), Q2 (82-91), and Q1 (≤81) were 1.81 (95% CI: 1.27-2.58, p=0.001), 1.23 (95% CI: 0.84-1.79, p=0.296), 2.27 (95% CI: 1.57-3.29, p<0.001), respectively. The relationship between GNRI and 90-day mortality demonstrates an L-shaped curve (p=0.016), with an approximate inflection point at 101.5. Conclusion: These findings imply that GNRI is a useful prognostic tool in older adults with COPD in the ICU. An L-shaped relationship was observed between GNRI and 90-day mortality in these patients.

Spatiotemporal role of SETD2-H3K36me3 in murine pancreatic organogenesis.

Pancreas development is tightly controlled by multilayer mechanisms. Despite years of effort, large gaps remain in understanding how histone modifications coordinate pancreas development. SETD2, a predominant histone methyltransferase of H3K36me3, plays a key role in embryonic stem cell differentiation, whose role in organogenesis remains elusive. Here, by combination of cleavage under targets and tagmentation (CUT&Tag), assay for transposase-accessible chromatin using sequencing (ATAC-seq), and bulk RNA sequencing, we show a dramatic increase in the H3K36me3 level from the secondary transition phase and decipher the related transcriptional alteration. Using single-cell RNA sequencing, we define that pancreatic deletion of Setd2 results in abnormalities in both exocrine and endocrine lineages: hyperproliferative tip progenitor cells lead to abnormal differentiation; Ngn3+ endocrine progenitors decline due to the downregulation of Nkx2.2, leading to insufficient endocrine development. Thus, these data identify SETD2 as a crucial player in embryonic pancreas development, providing a clue to understanding the dysregulation of histone modifications in pancreatic disorders.