Differential associations of risk factors with severe and non-severe hypoglycaemia: the Hypoglycaemia Assessment Tool prospective observational study in people with insulin-treated type 1 diabetes and type 2 diabetes.

AIM: To assess the differential association of risk factors with severe and non-severe hypoglycaemia. MATERIALS AND METHODS: The Hypoglycaemia Assessment Tool study evaluated the risk of hypoglycaemia over a 4-week period in patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) on insulin in 24 countries. Negative binomial regressions were applied to examine the associations of several risk factors with severe and non-severe hypoglycaemia. RESULTS: The median age was 41 years in 5949 patients with T1D and 62 years in 12 914 patients with T2D. The 4-week rates of non-severe hypoglycaemic were 5.57 and 1.40 episodes per person in T1D and T2D, respectively; the corresponding rates for severe hypoglycaemia were 0.94 and 0.30. The excess risk was 42% higher for severe than non-severe hypoglycaemia in females versus males with T2D; 27% higher in patients with T2D with versus without a continuous glucose monitoring (CGM); and 47% lower in patients with T1D with versus without an insulin pump. The excess risk also differed across geographical areas and was marginally lower for severe than non-severe hypoglycaemia for higher values of HbA1c in patients with T2D. Associations with severity of hypoglycaemia were not different for age, diabetes and insulin therapy duration, previous hypoglycaemic episodes and insulin regimen. CONCLUSIONS: The risk of severe versus non-severe hypoglycaemia differs in patients with T1D and T2D; sex, the use of a CGM and insulin pump, and geographical areas were differently associated with one type of hypoglycaemia than the other.

Association between childhood trauma and Internet gaming disorder: a moderated mediation analysis with depression as a mediator and psychological resilience as a moderator.

BACKGROUND: The effect of childhood trauma on Internet gaming disorder remains unclear. In this study, we examined this association in Chinese students and explored the possible associated roles of psychological resilience and depression. METHODS: In total, 8,579 students from Hunan Province, China, provided information regarding their sociodemographic factors, history of childhood trauma, any symptoms of depression, psychological resilience, and characteristics of Internet gaming disorder for this cross-sectional study. The impact of childhood trauma on Internet gaming disorder, as well as the extent to which it was mediated by depression and moderated by psychological resilience was evaluated. RESULTS: The influence of childhood trauma on Internet gaming disorder was partially mediated by depression (B = 0.07, 95% CI [0.04, 0.05], p < 0.001), with psychological resilience acting as a mitigating factor (B = -0.002, 95% CI [13.74, 21.72], p < 0.001). Psychological resilience also moderated the association between childhood trauma and depression (B = - 0.003, 95% CI [22.17, 28.10], p < 0.001). Our moderated mediation model elucidated psychosocial mechanisms, revealing the underlying link between childhood trauma and Internet gaming disorder. It also demonstrated the partial mediating role of depression and modulating role of psychological resilience among Chinese students. CONCLUSIONS: Education and interventions, along with effective social support, should be provided to enhance students' psychological resilience and prevent childhood trauma and depression.

Clcn3 deficiency ameliorates high-fat diet-induced obesity and improves metabolism in mice.

Objective: Obesity is defined as excess body fat and is a current health epidemic associated with increased risk for type 2 diabetes and cardiovascular disease. The ClC-3 chloride channel/antiporter, encoded by the Clcn3, is associated with some diseases, like carcinoma, nervous system diseases, and metabolic diseases. To verify the relationship between the Clcn3 and weight including metabolic changes, searching for a new target for metabolic therapy of obesity, we designed the experiment. Methods: The mice were divided into 4 different groups: Clcn3+/+ mice + high-fat diet (HFD), Clcn3-/- mice + HFD, Clcn3+/+ mice + normal diet (ND), Clcn3-/- mice + ND, and fed for 16 weeks. After the glucose tolerance test and insulin tolerance test, peripheral blood and adipose tissues were collected. Moreover, we performed transcriptome sequencing for the epididymal white adipose tissue from Clcn3+/+ and Clcn3-/- mice with the high-fat diet. Western blotting verified the changes in protein levels of relevant metabolic genes. Results: We found that the Clcn3-/- mice had lower body weight and visceral fat, refining glucose and lipid metabolism in HFD-induced mice, but had no effect in normal diet mice. RNA-seq and Western blotting indicated that Clcn3 deficiency may inhibit obesity through the AMPK-UCP1 axis. Conclusion: Modulation of Clcn3 may provide an appealing therapeutic target for obesity and associated metabolic syndrome.

Ultra-highly sensitive dual gases detection based on photoacoustic spectroscopy by exploiting a long-wave, high-power, wide-tunable, single-longitudinal-mode solid-state laser.

Photoacoustic spectroscopy (PAS) as a highly sensitive and selective trace gas detection technique has extremely broad application in many fields. However, the laser sources currently used in PAS limit the sensing performance. Compared to diode laser and quantum cascade laser, the solid-state laser has the merits of high optical power, excellent beam quality, and wide tuning range. Here we present a long-wave, high-power, wide-tunable, single-longitudinal-mode solid-state laser used as light source in a PAS sensor for trace gas detection. The self-built solid-state laser had an emission wavelength of ~2 µm with Tm:YAP crystal as the gain material, with an excellent wavelength and optical power stability as well as a high beam quality. The wide wavelength tuning range of 9.44 nm covers the absorption spectra of water and ammonia, with a maximum optical power of ~130 mW, allowing dual gas detection with a single laser source. The solid-state laser was used as light source in three different photoacoustic detection techniques: standard PAS with microphone, and external- and intra-cavity quartz-enhanced photoacoustic spectroscopy (QEPAS), proving that solid-state laser is an attractive excitation source in photoacoustic spectroscopy.

Quasi-distributed quartz enhanced photoacoustic spectroscopy sensing based on hollow waveguide micropores.

In this Letter, a quasi-distributed quartz enhanced photoacoustic spectroscopy (QEPAS) gas sensing system based on hollow waveguide micropores (HWGMP) was reported for the first time, to the best of our knowledge. Three micropores were developed on the HWG to achieve distributed detection units. Three self-designed quartz tuning forks (QTFs) with low resonant frequency of 8.7 kHz were selected as the acoustic wave transducer to improve the detection performance. Compared with micro-nano fiber evanescent wave (FEW) QEPAS, the HWGMP-QEPAS sensor has advantages such as strong anti-interference ability, low loss, and low cost. Acetylene (C2H2) was selected as the target gas to verify the characteristics of the reported sensor. The experimental results showed that the three QTFs almost had the same sensing ability and possessed an excellent linear concentration response to C2H2. The minimum detection limits (MDLs) for the three QTFs were determined as 68.90, 68.31, and 66.62 ppm, respectively. Allan deviation analysis indicated that the system had good long-term stability, and the MDL can be improved below 3 ppm in an average time of 1000 s.

Construction of Multi-enzyme Integrated Catalysts for Deracemization of Cyclic Chiral Amines.

Multi-enzyme cascade catalysis has become an important technique for chemical reactions used in manufacturing and scientific study. In this research, we designed a four-enzyme integrated catalyst and used it to catalyse the racemization reaction of cyclic chiral amines, where monoamine oxidase (MAO) catalyses the selective oxidation of 1-methyl-1,2,3,4-tetrahydroisoquinoline (MTQ), imine reductase (IRED) catalyses the selective reduction of 1-methyl-3,4-dihydroisoquinoline (MDQ), formate dehydrogenase (FDH) is used for the cyclic regeneration of cofactors, and catalase (CAT) is used for decomposition of oxidative reactions. The four enzymes were immobilized via polydopamine (PDA)-encapsulated dendritic organosilica nanoparticles (DONs) as carriers, resulting in the amphiphilic core-shell catalysts. The hydrophilic PDA shell ensures the dispersion of the catalyst in water, and the hydrophobic DON core creates a microenvironment with the spatial confinement effect of the organic substrate and the preconcentration effect to enhance the stability of the enzymes and the catalytic efficiency. The core-shell structure improves the stability and reusability of the catalyst and rationally arranges the position of different enzymes according to the reaction sequence to improve the cascade catalytic performance and cofactor recovery efficiency.

Quercetin inhibits neuronal Ferroptosis and promotes immune response by targeting lipid metabolism-related gene PTGS2 to alleviate breast cancer-related depression.

BACKGROUND: Quercetin, the key ingredient in Xiaoyao Kangai Jieyu Formula, has been previously found to relieve breast cancer-related depression (BCRD). PURPOSE: We want to explore the potential mechanisms and therapeutic targets of quercetin alleviating BCRD. METHODS: BALB/c mice were injected subcutaneously with 4T1 cells and corticosterone (CORT) to create a BCRD mice model. The primary hippocampal neurons were co-induced with 10 µg/ml lipopolysaccharide (LPS) and 200 µM CORT for 6 h to establish an in vitro model of BCRD. Quercetin was applied to explore its effect on disease symptoms, gut microbiota, and lipid metabolism of BCRD mice. Lipid metabolism-related genes were screened based on network pharmacology. Molecular docking was employed to prove whether quercetin bound to prostaglandin-endoperoxide synthase 2 (PTGS2). PTGS2 overexpression was carried out to explore the underlying mechanism of quercetin treatment on BCRD. RESULTS: Quercetin treatment not only altered the composition and abundance of gut microbiota but also alleviated abnormal lipid metabolism in BCRD mice. In particular, quercetin down-regulated BCRD and lipid metabolism-related genes screened by network pharmacology, especially PTGS2. Further, molecular docking verified the stable binding between quercetin and PTGS2. In hippocampal neurons, quercetin promoted proliferation but reduced ferroptosis-related markers (total Fe, Fe2+, MDA, and ROS) levels by targeting PTGS2. In BCRD mice, quercetin reduced the high immobility time and increased the sucrose preference rate and serotonin (5-HT), dopamine (DA), and noradrenaline (NE) levels. Meanwhile, quercetin increased CD4+/CD8+ T cells ratio and IL-2 and IFN-γ levels but reduced CA153 and IL-10 levels to alleviate BCRD development. However, PTGS2 overexpression reversed these effects of quercetin on BCRD. CONCLUSION: Quercetin inhibited neuronal ferroptosis and promoted immune responses in BCRD mice by targeting the lipid metabolism-related gene PTGS2. This provided a reference for quercetin in the treatment of BCRD.

Barriers and facilitators to technology acceptance of socially assistive robots in older adults - A qualitative study based on the capability, opportunity, and motivation behavior model (COM-B) and stakeholder perspectives.

This study aimed to identify barriers and facilitators to older adults' acceptance of socially assistive robots from a stakeholder perspective. We enlisted 36 distinct stakeholders, including older adult, nurses, retirement home managers, and employees from robotics companies. Data collection was conducted through semi-structured interviews. The research findings were mapped onto the Capability, Opportunity, Motivation-Behavior (COM-B) model. We obtained a total of 14 facilitators and barriers. (1) Capability: High technological familiarity (Facilitator); insufficient technical experience and low level of education (Barriers). (2) Motivation: Strong interest in new things, perceived convenience usefulness, and emotional support (Facilitators); concerns about technical reliability, perceived lack of ease of use, inability to establish emotional connection, and low level of need (Barriers). (3) Opportunity: Insufficient policy support and economic capacity, robotics technical problems (Barriers). Collaborative efforts among stakeholders are vital for fostering an environment conducive to socially assistive robot adoption, maximizing its potential to improve older adults' well-being.

Probucol mitigates high-fat diet-induced cognitive and social impairments by regulating brain redox and insulin resistance.

Probucol has been utilized as a cholesterol-lowering drug with antioxidative properties. However, the impact and fundamental mechanisms of probucol in obesity-related cognitive decline are unclear. In this study, male C57BL/6J mice were allocated to a normal chow diet (NCD) group or a high-fat diet (HFD) group, followed by administration of probucol to half of the mice on the HFD regimen. Subsequently, the mice were subjected to a series of behavioral assessments, alongside the measurement of metabolic and redox parameters. Notably, probucol treatment effectively alleviates cognitive and social impairments induced by HFD in mice, while exhibiting no discernible influence on mood-related behaviors. Notably, the beneficial effects of probucol arise independently of rectifying obesity or restoring systemic glucose and lipid homeostasis, as evidenced by the lack of changes in body weight, serum cholesterol levels, blood glucose, hyperinsulinemia, systemic insulin resistance, and oxidative stress. Instead, probucol could regulate the levels of nitric oxide and superoxide-generating proteins, and it could specifically alleviate HFD-induced hippocampal insulin resistance. These findings shed light on the potential role of probucol in modulating obesity-related cognitive decline and urge reevaluation of the underlying mechanisms by which probucol exerts its beneficial effects.

Long-Term Follow-Up of Patients Undergoing Thalidomide Therapy for Transfusion-Dependent ß-Thalassaemia: A Single-Center Experience.

Objective: We evaluated the long-term safety and efficacy of thalidomide in the treatment of transfusion-dependent ß-thalassemia (TDT). Methods: Fifty patients with TDT were treated with thalidomide and followed-up for 5 years. Thalidomide at a 50 mg dose was administered once a day after dinner. The dose was increased to 150 mg/d after 3 d if well tolerated. After 1 year of treatment, the hemoglobin (Hb) level was stabilized at its maximum, and thalidomide was gradually reduced and maintained at the minimum dose. The hematological response, transfusion dependence, and haemolytic indicators were assessed. Results: At 9 month of follow-up, 38 (76%) patients achieved an excellent response, 1 (2%) a good response, 4(8%) a minor response, and 7(14%) did not show a response. The overall response rate was 86%. At 9 months, the Hb level increased from 79.0 ± 13.2 g/L at baseline to 99.0 ± 13.7g/L (P<0.001). Patients who achieved excellent response continued to show an increase in Hb levels during follow-up. At 48 months, the mean Hb level was 98.99 ± 10.3g/L; 21 patients (84.0%) became transfusion independent. Thalidomide was reduced and maintained to 25 mg/d in three of these patients. Moreover, five patients completed 60 months of follow-up, and with a mean Hb level of 99.8 ± 6.7g/L. During follow-up, grade 1-2 adverse drug reactions were noted; however, no grade 3 or higher adverse event was reported. However, no decrease in hemolytic indicators was observed. Conclusion: Thalidomide was well tolerated in the long term, while it significantly improved Hb levels and reduced the transfusion burden.

3D Gaussian Splatting as New Era: A Survey.

3D Gaussian Splatting (3D-GS) has emerged as a significant advancement in the field of Computer Graphics, offering explicit scene representation and novel view synthesis without the reliance on neural networks, such as Neural Radiance Fields (NeRF). This technique has found diverse applications in areas such as robotics, urban mapping, autonomous navigation, and virtual reality/augmented reality, just name a few. Given the growing popularity and expanding research in 3D Gaussian Splatting, this paper presents a comprehensive survey of relevant papers from the past year. We organize the survey into taxonomies based on characteristics and applications, providing an introduction to the theoretical underpinnings of 3D Gaussian Splatting. Our goal through this survey is to acquaint new researchers with 3D Gaussian Splatting, serve as a valuable reference for seminal works in the field, and inspire future research directions, as discussed in our concluding section.

Do not stumble over the same "stone" twice: a case series of endogenous endophthalmitis secondary to severe systemic diseases.

BACKGROUND: Endogenous endophthalmitis (EE) is a rare but highly destructive eye emergency secondary to systemic infection. Acute endophthalmitis can lead to irreversible vision impairment or even loss of the whole eye, unless being diagnosed and treated promptly. CASE PRESENTATION: This study reports three typical EE cases of endogenous endophthalmitis secondary to different severe systemic diseases. Patients were recruited from the Department of ophthalmology at Zhongnan hospital of Wuhan University and the Department of ophthalmology at the Second Affiliated Hospital of Fujian Medical University. Patients were followed up for up to 60 days. Among these cases, the eye symptoms is the initial manifestations while secondary to original different special systemic conditions. Patients have been treated under dynamically prompt response undergoing systemic treatment and eye treatment at the same time. Best corrected visual acuity were 20/40, 20/60 and light perception during follow-up evaluation. CONCLUSIONS: Our observation suggest that prompt identification and treatment could save patients' vision from EE.

HtrA3 paves the way for MSC migration and promotes osteogenesis.

Mesenchymal stem cell (MSC) migration determines the healing capacity of bone and is crucial in promoting bone regeneration. Migration of MSCs is highly dependent on degradation of extracellular matrix by proteolytic enzymes. However, the underlying mechanisms of how enzymolysis paves the way for MSCs to migrate from their niche to the defect area is still not fully understood. Here, this study shows that high-temperature requirement A3 (HtrA3) overcomes the physical barrier and provides anchor points through collagen IV degradation, paving the way for MSC migration. HtrA3 is upregulated in MSCs at the leading edge of bone defect during the early stage of healing. HtrA3 degrades the surrounding collagen IV, which increases the collagen network porosity and increases integrin ß1 expression. Subsequently, integrin ß1 enhances the mechanotransduction of MSCs, thus remodeling the cytoskeleton, increasing cellular stiffness and nuclear translocation of YAP, eventually promoting the migration and subsequent osteogenic differentiation of MSCs. Local administration of recombinant HtrA3 in rat cranial bone defects significantly increases new bone formation and further validates the enhancement of MSC migration. This study helps to reveal the novel roles of HtrA3, explore potential targets for regenerative medicine, and offer new insights for the development of bioactive materials.

A retrospective study of an irradiation-based conditioning regimen and chidamide maintenance therapy in T-ALL/LBL.

OBJECTIVES: T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL) are highly malignant and aggressive hematologic tumors for which there is no standard first-line treatment. Chidamide, a novel histone deacetylase inhibitor, shows great promise. We assessed the efficacy and safety of an irradiation-containing conditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT) and post-transplantation chidamide maintenance in patients with T-ALL/LBL. METHODS: We retrospectively analyzed the clinical data of six patients with T-ALL/LBL who underwent allo-HSCT with a radiotherapy-containing pretreatment regimen and post-transplant chidamide maintenance therapy. The endpoints were relapse, graft-versus-host disease (GVHD), transplant-related mortality (TRM), progression-free survival (PFS), overall survival (OS), and adverse events (AEs). RESULTS: All of the patients had uneventful post-transplant hematopoietic reconstitution, and all achieved complete molecular remission within 30 days. All six patients survived, and two relapsed with a median relapse time of 828.5 (170-1335) days. The 1-year OS rate was 100%, the 2-year PFS rate was 66.7%, and the TRM rate was 0%. After transplantation, two patients developed grade I-II acute GVHD (2/6); grade III-IV acute and chronic GVHD were not observed. The most common AEs following chidamide administration were hematological AEs, which occurred to varying degrees in all patients; liver function abnormalities occurred in two patients (grade 2), and symptoms of malaise occurred in one patient (grade 1). CONCLUSION: Chidamide maintenance therapy after T-ALL/LBL transplantation is safe, but the efficacy needs to be further investigated.

Exploring miR-21 as a key regulator in two distinct approaches of bone marrow stromal cells differentiation into Schwann-like cells.

The differentiation of bone marrow stromal cells (BMSCs) into Schwann-like cells (SCLCs) has the potential to promote the structural and functional restoration of injured axons. However, the optimal induction protocol and its underlying mechanisms remain unclear. This study aimed to compare the effectiveness of different induction protocols in promoting the differentiation of rat BMSCs into SCLCs and to explore their potential mechanisms. BMSCs were induced using two distinct methods: a composite factor induction approach (Protocol-1) and a conditioned culture medium induction approach (Protocol-2). The expression of Schwann cells (SCs) marker proteins and neurotrophic factors (NTFs) in the differentiated cells was assessed. Cell proliferation and apoptosis were also measured. During induction, changes in miR-21 and Sprouty RTK signaling antagonist 2 (SPRY2) mRNA were analyzed. Following the transfection of BMSCs with miR-21 agomir or miR-21 antagomir, induction was carried out using both protocols, and the expression of SPRY2, ERK1/2, and SCs marker proteins was examined. The results revealed that NTFs expression was higher in Protocol-1, whereas SCs marker proteins expression did not significantly differ between the two groups. Compared to Protocol-1, Protocol-2 exhibited enhanced cell proliferation and fewer apoptotic and necrotic cells. Both protocols showed a negative correlation between miR-21 and SPRY2 expression throughout the induction stages. After induction, the miR-21 agomir group exhibited reduced SPRY2 expression, increased ERK1/2 expression, and significantly elevated expression of SCs marker proteins. This study demonstrates that Protocol-1 yields higher NTFs expression, whereas Protocol-2 results in stronger SCLCs proliferation. Upregulating miR-21 suppresses SPRY2 expression, activates the ERK1/2 signaling pathway, and promotes BMSC differentiation into SCLCs.

Mortality of Patients With Sepsis Administered Piperacillin-Tazobactam vs Cefepime.

Importance: Experimental and observational studies have suggested that empirical treatment for bacterial sepsis with antianaerobic antibiotics (eg, piperacillin-tazobactam) is associated with adverse outcomes compared with anaerobe-sparing antibiotics (eg, cefepime). However, a recent pragmatic clinical trial of piperacillin-tazobactam and cefepime showed no difference in short-term outcomes at 14 days. Further studies are needed to help clarify the empirical use of these agents. Objective: To examine the use of piperacillin-tazobactam compared with cefepime in 90-day mortality in patients treated empirically for sepsis, using instrumental variable analysis of a 15-month piperacillin-tazobactam shortage. Design, Setting, and Participants: In a retrospective cohort study, hospital admissions at the University of Michigan from July 1, 2014, to December 31, 2018, including a piperacillin-tazobactam shortage period from June 12, 2015, to September 18, 2016, were examined. Adult patients with suspected sepsis treated with vancomycin and either piperacillin-tazobactam or cefepime for conditions with presumed equipoise between piperacillin-tazobactam and cefepime were included in the study. Data analysis was conducted from December 17, 2022, to April 11, 2023. Main Outcomes and Measures: The primary outcome was 90-day mortality. Secondary outcomes included organ failure-free, ventilator-free, and vasopressor-free days. The 15-month piperacillin-tazobactam shortage period was used as an instrumental variable for unmeasured confounding in antibiotic selection. Results: Among 7569 patients (4174 men [55%]; median age, 63 [IQR 52-73] years) with sepsis meeting study eligibility, 4523 were treated with vancomycin and piperacillin-tazobactam and 3046 were treated with vancomycin and cefepime. Of patients who received piperacillin-tazobactam, only 152 (3%) received it during the shortage. Treatment groups did not differ significantly in age, Charlson Comorbidity Index score, Sequential Organ Failure Assessment score, or time to antibiotic administration. In an instrumental variable analysis, piperacillin-tazobactam was associated with an absolute mortality increase of 5.0% at 90 days (95% CI, 1.9%-8.1%) and 2.1 (95% CI, 1.4-2.7) fewer organ failure-free days, 1.1 (95% CI, 0.57-1.62) fewer ventilator-free days, and 1.5 (95% CI, 1.01-2.01) fewer vasopressor-free days. Conclusions and Relevance: Among patients with suspected sepsis and no clear indication for antianaerobic coverage, administration of piperacillin-tazobactam was associated with higher mortality and increased duration of organ dysfunction compared with cefepime. These findings suggest that the widespread use of empirical antianaerobic antibiotics in sepsis may be harmful.

Impairment of olfactory identification ability in ultra-high risk for psychosis and drug-naïve first episode psychosis.

OBJECTIVE: Patients with psychotic diseases have been reported to exhibit abnormalities in their olfactory discrimination. These alterations have also been identified in people at high genetic or clinical risk for psychosis, suggesting olfactory discrimination dysfunction may be a potential risk factor for developing psychosis. Thus, the purpose of our study is to explore the difference in olfactory discrimination ability in the prosal stage and early stage of psychosis and to explore the potential risk factor of developed psychosis. METHODS: We compared olfactory identification and cognitive function in 89 ultra-high-risk (UHR) individuals, 103 individuals with Drug-naïve first-episode schizophrenia (FES), 81 genetic high-risk (GHR) individuals, and 97 healthy controls (HC). Additionally, we compared olfactory identification and cognitive function between two groups; UHR individuals who later transitioned to psychosis (UHR-T; n = 33) and those who did not transition (UHR-NT; n = 42)). Furthermore, we analyzed the correlations between olfactory discrimination ability and cognitive function and symptoms and compared the olfactory function between men and women. RESULTS: Patients with first-episode schizophrenia (FES) and those at ultra-high risk (UHR) for psychosis exhibited more significant deficits in olfactory identification than healthy controls (HC), while no differences in olfactory identification dysfunction were observed between the genetic high risk (GHR) and HC groups. Notably, individuals in the UHR group who later developed psyhchosis displayed a steeper marked decline in their baseline olfactory identification ability than that of those in the UHR group who did not develop psychosis. Cognitive dysfunction is widely observed in both the FES and UHR groups, with a distinct correlation identified between olfactory discrimination function and cognitive performance. Finally, overall, women exhibit significantly superior olfactory function than men. CONCLUSION: In conclusion, these findings suggest that impairment of olfactory identification exists in the early stage of psychosis. Olfactory identification dysfunction may therefore be a potential marker of predicting the transition to schizophrenia.

The potential of machine learning models to identify malnutrition diagnosed by GLIM combined with NRS-2002 in colorectal cancer patients without weight loss information.

BACKGROUND & AIMS: The key step of the Global Leadership Initiative on Malnutrition (GLIM) is nutritional risk screening, while the most appropriate screening tool for colorectal cancer (CRC) patients is yet unknown. The GLIM diagnosis relies on weight loss information, and bias or even failure to recall patients' historical weight can cause misestimates of malnutrition. We aimed to compare the suitability of several screening tools in GLIM diagnosis, and establish machine learning (ML) models to predict malnutrition in CRC patients without weight loss information. METHODS: This multicenter cohort study enrolled 4487 CRC patients. The capability of GLIM diagnoses combined with four screening tools in predicting survival probability was compared by Kaplan-Meier curves, and the most accurate one was selected as the malnutrition reference standard. Participants were randomly assigned to a training cohort (n = 3365) and a validation cohort (n = 1122). Several ML approaches were adopted to establish models for predicting malnutrition without weight loss data. We estimated feature importance and reserved the top 30% of variables for retraining simplified models. The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity were calculated to assess and compare model performance. RESULTS: NRS-2002 was the most suitable screening tool for GLIM diagnosis in CRC patients, with the highest hazard ratio (1.59; 95% CI, 1.43-1.77). A total of 2076 (46.3%) patients were malnourished diagnosed by GLIM combined with NRS-2002. The simplified random forest (RF) model outperformed other models with an AUC of 0.830 (95% CI, 0.805-0.854), and accuracy, sensitivity and specificity were 0.775, 0.835 and 0.742, respectively. We deployed an online application based on the simplified RF model to accurately estimate malnutrition probability in CRC patients without weight loss information (https://zzuwtt1998.shinyapps.io/dynnomapp/). CONCLUSIONS: Nutrition Risk Screening 2002 was the optimal initial nutritional risk screening tool in the GLIM process. The RF model outperformed other models, and an online prediction tool was developed to properly identify patients at high risk of malnutrition.

The roles and mechanisms of SREBP1 in cancer development and drug response.

Cancer occurrence and development are closely related to increased lipid production and glucose consumption. Lipids are the basic component of the cell membrane and play a significant role in cancer cell processes such as cell-to-cell recognition, signal transduction, and energy supply, which are vital for cancer cell rapid proliferation, invasion, and metastasis. Sterol regulatory element-binding transcription factor 1 (SREBP1) is a key transcription factor regulating the expression of genes related to cholesterol biosynthesis, lipid homeostasis, and fatty acid synthesis. In addition, SREBP1 and its upstream or downstream target genes are implicated in various metabolic diseases, particularly cancer. However, no review of SREBP1 in cancer biology has yet been published. Herein, we summarized the roles and mechanisms of SREBP1 biological processes in cancer cells, including SREBP1 modification, lipid metabolism and reprogramming, glucose and mitochondrial metabolism, immunity, and tumor microenvironment, epithelial-mesenchymal transition, cell cycle, apoptosis, and ferroptosis. Additionally, we discussed the potential role of SREBP1 in cancer prognosis, drug response such as drug sensitivity to chemotherapy and radiotherapy, and the potential drugs targeting SREBP1 and its corresponding pathway, elucidating the potential clinical application based on SREBP1 and its corresponding signal pathway.

Optimal Treatment Parameters for Ultrasound-Stimulated Microbubbles in Upregulating Proliferation and Stemness of Bone Marrow Mesenchymal Stem Cells.

OBJECTIVES: Ultrasound-targeted microbubble disruption (UTMD) is a widely used technique to improve the differentiation and proliferation capacity of mesenchymal stem cells (MSCs), but the optimal therapeutic parameters for UTMD are unclear. In this study, we aimed to find the appropriate peak negative pressure (PNP), which is a key parameter for enhancing the stemness properties and proliferation of MSCs. METHODS: Experiments were performed in UTMD group, ultrasound (US) group under different PNP exposure conditions (0.5, 1.0, and 1.5 MPa), and control group. Apoptosis safety was analyzed by flow cytometry and MSC proliferation was measured at 12, 24, and 36 hours after irradiation by cell counting kit 8. The expression of the stemness genes NANOG, OCT-4, and SOX-2 were determined by enzyme-linked immunosorbent assay (ELISA) or reverse transcription polymerase chain reaction. RESULTS: The results showed that the 1.5 MPa UTMD-treated group had the highest proliferation capacity of MSCs at 24 hours. ELISA or quantitative reverse transcription polymerase chain reaction results showed that UTMD treatment of the 1.5 MPa group significantly upregulated the expression of the stemness genes NANOG, SOX-2, and OCT-4. CONCLUSIONS: In conclusion, the appropriate peak PNP value of UTMD was 1.5 MPa, and 1.5 MPa-mediated UTMD group obviously promoted MSCs proliferation and maintained stemness by upregulating the expression of stemness genes.