A deep learning model, NAFNet, predicts adverse pathology and recurrence in prostate cancer using MRIs.

We aimed to apply a potent deep learning network, NAFNet, to predict adverse pathology events and biochemical recurrence-free survival (bRFS) based on pre-treatment MRI imaging. 514 prostate cancer patients from six tertiary hospitals throughout China from 2017 and 2021 were included. A total of 367 patients from Fudan University Shanghai Cancer Center with whole-mount histopathology of radical prostatectomy specimens were assigned to the internal set, and cancer lesions were delineated with whole-mount pathology as the reference. The external test set included 147 patients with BCR data from five other institutes. The prediction model (NAFNet-classifier) and integrated nomogram (DL-nomogram) were constructed based on NAFNet. We then compared DL-nomogram with radiology score (PI-RADS), and clinical score (Cancer of the Prostate Risk Assessment score (CAPRA)). After training and validation in the internal set, ROC curves in the external test set showed that NAFNet-classifier alone outperformed ResNet50 in predicting adverse pathology. The DL-nomogram, including the NAFNet-classifier, clinical T stage and biopsy results, showed the highest AUC (0.915, 95% CI: 0.871-0.959) and accuracy (0.850) compared with the PI-RADS and CAPRA scores. Additionally, the DL-nomogram outperformed the CAPRA score with a higher C-index (0.732, P < 0.001) in predicting bRFS. Based on this newly-developed deep learning network, NAFNet, our DL-nomogram could accurately predict adverse pathology and poor prognosis, providing a potential AI tools in medical imaging risk stratification.

Development Trend in Composition Optimization, Microstructure Manipulation, and Strengthening Methods of Die Steels under Lightweight and Integrated Die Casting.

In the general environment of lightweight automobiles, the integrated die-casting technology proposed by Tesla has become the general mode to better achieve weight reduction in automobiles. The die-casting mold required by integrated die-casting technology has the characteristics of large scale and complexity. Hence, higher requirements are put forward for the comprehensive performance of the die steel. Despite the stagnation in the progress of conventional strengthening methods, enhancing the performance of die steel has become increasingly challenging. Indeed, it necessitates exploring novel die steel and optimizing heat treatment and reinforcement technologies. This article summarizes and analyzes the development status of die steel and corresponding heat treatment and microstructure manipulation as well as strengthening methods and elaborates on an excellent nano-strengthening technology. Furthermore, this review will aid researchers in establishing a comprehensive understanding of the development status of die steel and the processes utilized for its strengthening. It will also assist them in developing die steel with improved comprehensive performance to meet the high demand for mold steel in the integrated die-casting technology of the new era.

Multi-integrated approach for unraveling small open reading frames potentially associated with secondary metabolism in Streptomyces.

IMPORTANCE: Due to their small size and special chemical features, small open reading frame (smORF)-encoding peptides (SEPs) are often neglected. However, they may play critical roles in regulating gene expression, enzyme activity, and metabolite production. Studies on bacterial microproteins have mainly focused on pathogenic bacteria, which are importance to systematically investigate SEPs in streptomycetes and are rich sources of bioactive secondary metabolites. Our study is the first to perform a global identification of smORFs in streptomycetes. We established a peptidogenomic workflow for non-model microbial strains and identified multiple novel smORFs that are potentially linked to secondary metabolism in streptomycetes. Our multi-integrated approach in this study is meaningful to improve the quality and quantity of the detected smORFs. Ultimately, the workflow we established could be extended to other organisms and would benefit the genome mining of microproteins with critical functions for regulation and engineering useful microorganisms.

Skeletal Editing of Dibenzolactones to Fluorenes via Ni- or Pd-Catalyzed Decarboxylation.

The skeletal editing of dibenzolactones to fluorenes by Ni- or Pd-catalyzed decarboxylation is reported. In contrast to previously reported intramolecular decarboxylative couplings, inductively electron-withdrawing ortho substituents on the aryl carboxylate moiety and metal additives are not required. The decarboxylation reaction proceeds cleanly and can be applied to the skeletal editing of a natural product analogue. Mechanistic observations are consistent with stabilization of the carboxylate-ligated Ni complex over the Ni-carboxylate ion pair, which is the key factor in promoting the challenging decarboxylation step in the catalytic cycle.

O-GlcNAc transferase in astrocytes modulates depression-related stress susceptibility through glutamatergic synaptic transmission.

Major depressive disorder is a common and devastating psychiatric disease, and the prevalence and burden are substantially increasing worldwide. Multiple studies of depression patients have implicated glucose metabolic dysfunction in the pathophysiology of depression. However, the molecular mechanisms by which glucose and related metabolic pathways modulate depressive-like behaviors are largely uncharacterized. Uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) is a glucose metabolite with pivotal functions as a donor molecule for O-GlcNAcylation. O-GlcNAc transferase (OGT), a key enzyme in protein O-GlcNAcylation, catalyzes protein posttranslational modification by O-GlcNAc and acts as a stress sensor. Here, we show that Ogt mRNA was increased in depression patients and that astroglial OGT expression was specifically upregulated in the medial prefrontal cortex (mPFC) of susceptible mice after chronic social-defeat stress. The selective deletion of astrocytic OGT resulted in antidepressant-like effects, and moreover, astrocytic OGT in the mPFC bidirectionally regulated vulnerability to social stress. Furthermore, OGT modulated glutamatergic synaptic transmission through O-GlcNAcylation of glutamate transporter-1 (GLT-1) in astrocytes. OGT astrocyte-specific knockout preserved the neuronal morphology atrophy and Ca2+ activity deficits caused by chronic stress and resulted in antidepressant effects. Our study reveals that astrocytic OGT in the mPFC regulates depressive-like behaviors through the O-GlcNAcylation of GLT-1 and could be a potential target for antidepressants.

Transitions in Frailty and 4-Year Mortality Risk in Taiwan Longitudinal Study on Aging.

OBJECTIVES: To explore the associations of (1) the frailty phenotype or frailty index transition with cause-specific mortality, and (2) different combinations of transition in frailty phenotype and frailty index with all-cause mortality. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Data from 3529 respondents aged >50 years who completed the 1999 and 2003 surveys of the Taiwan Longitudinal Study on Aging were analyzed. METHODS: Cox regression and subdistribution hazard models were constructed to investigate frailty phenotype or frailty index transitions (by categories of frailty phenotype, absolute and percentage changes in frailty index, and combined categories of the 2 measurements) and subsequent 4-year all-cause and cause-specific mortality, respectively. RESULTS: Among the frailty phenotype transition groups, the improved frailty group had overall mortality risk comparable to that of the maintained robustness/prefrailty group [hazard ratio (HR): 0.9; 95% CI: 0.7-1.2] and lower risk of mortality due to organ failure (HR: 0.4; 95% CI: 0.2-0.8; P = .015), whereas the worsened frailty group had the highest risk of all-cause mortality and death from infection, malignancy, cardiometabolic/cerebrovascular diseases, and other causes (HR: 1.8-3.7; all P < .03). The rapidly increased frailty index group had significantly higher all-cause and every cause-specific mortality than the decreased frailty index group (HR: 1.8-7.7; all P < .05). When frailty phenotype and frailty index transition groups were combined, participants with worsened frailty/rapidly increased frailty index had increased risk under the same frailty index/frailty phenotype transition condition, particularly for large changes in each factor (HR: 1.5-2.2; P < .01 for worsened frailty; 1.7-4.5, P < .03 for rapidly increased frailty index). CONCLUSIONS AND IMPLICATIONS: We found that considering both frailty phenotype and frailty index provided best mortality prediction. These associations were independent of baseline frailty status and comorbidities. Nevertheless, even capturing transitions in frailty phenotype or frailty index only can provide good mortality prediction, which supported adopting these approaches in different clinical settings.

Early cholecystectomy following percutaneous transhepatic gallbladder drainage is effective for moderate to severe acute cholecystitis in the octogenarians.

BACKGROUND: Acute cholecystitis (AC) is a life-threatening infectious/inflammatory disease in older patients. This study aimed to investigate the safety and optimal timing of surgery in patients aged ≥ 80 years with moderate to severe AC who received percutaneous transhepatic gallbladder drainage (PTGBD). METHODS: From January 2008 to February 2021, 152 patients were retrospectively enrolled. Clinical outcomes were compared among patients who received laparoscopic cholecystectomy (LC), open cholecystectomy (OC), and conversion surgery, and between those who received early (< 6 weeks after PTGBD) and delayed cholecystectomy (≥ 6 weeks after PTGBD). Logistic regression analysis was used to identify risk factors for recurrent AC, further biliary events, conversion, and perioperative complications. RESULTS: Sixty-seven patients underwent LC, 62 underwent OC, and 23 underwent conversion surgery. Operation-related complications and mortality rates did not differ among the types of surgery; however, LC group had shorter operative time than the other groups. Eighty-two patients underwent early cholecystectomy, while 70 underwent delayed cholecystectomy. There were no differences in operative time, operation-related complications, and mortality rates between the groups. However, higher rates of recurrent AC and biliary events were observed in the delayed cholecystectomy group (52.9% vs. 4.9% and 57.1% vs. 8.5%, p < 0.001). On multivariate analysis, delayed cholecystectomy was a significant risk factor for recurrent AC (odds ratio [OR] = 19.42, p < 0.001) and further biliary events (OR = 15.95, p < 0.001). CONCLUSIONS: Early cholecystectomy is recommended for patients aged ≥ 80 years with moderate to severe AC following PTGBD.

Targeting CD38 to Suppress Osteoarthritis Development and Associated Pain After Joint Injury in Mice.

OBJECTIVE: This study was undertaken to determine the role of CD38, which can function as an enzyme to degrade NAD+ , in osteoarthritis (OA) development. METHODS: Human knee cartilage from normal donors and OA donors were examined for CD38 expression. "Gain-of-function," through overexpression of CD38 via transient transfection, and "loss-of-function," through pharmacologic inhibition of CD38, approaches were used to assess the effects of CD38 on intracellular NAD+ :NADH ratio and catabolic activity in chondrocytes. We also initiated joint injury-induced OA by surgical destabilization of the medial meniscus (DMM) in CD38 knockout mice and wild-type (WT; C57BL/6) mice and in WT male mice in the presence or absence of apigenin treatment. Cartilage degradation, synovial inflammation, subchondral bone changes, and pain behavior were evaluated after DMM surgery. We also examined expression of CD38 and the neuropeptide calcitonin gene-related peptide (CGRP) in knee sections from these mice. RESULTS: CD38 expression was up-regulated in human knee OA cartilage and in chondrocytes stimulated with the proinflammatory cytokine interleukin-1ß (IL-1ß). Overexpression of CD38 in chondrocytes resulted in reduced cellular NAD+ :NADH ratio and augmented catabolic responses to IL-1ß. These effects were reversed by pharmacologic inhibition of CD38. Cartilage degradation and synovial inflammation, associated with increased CD38 expression in cartilage and synovium, osteophyte formation and subchondral bone sclerosis, and pain-like behavior linked to increased CGRP expression in the synovium were observed in WT mice after joint injury. Such effects were significantly reduced in mice deficient in CD38 through either genetic knockout or pharmacologic inhibition. CONCLUSION: CD38 deficiency exerts OA disease-modifying effects. Inhibition of CD38 has the potential to be a novel therapeutic approach for OA treatment.

Astrocyte dysfunction drives abnormal resting-state functional connectivity in depression.

Major depressive disorder (MDD) is a devastating mental disorder that affects up to 17% of the population worldwide. Although brain-wide network-level abnormalities in MDD patients via resting-state functional magnetic resonance imaging (rsfMRI) exist, the mechanisms underlying these network changes are unknown, despite their immense potential for depression diagnosis and management. Here, we show that the astrocytic calcium-deficient mice, inositol 1,4,5-trisphosphate-type-2 receptor knockout mice (Itpr2-/- mice), display abnormal rsfMRI functional connectivity (rsFC) in depression-related networks, especially decreased rsFC in medial prefrontal cortex (mPFC)-related pathways. We further uncover rsFC decreases in MDD patients highly consistent with those of Itpr2-/- mice, especially in mPFC-related pathways. Optogenetic activation of mPFC astrocytes partially enhances rsFC in depression-related networks in both Itpr2-/- and wild-type mice. Optogenetic activation of the mPFC neurons or mPFC-striatum pathway rescues disrupted rsFC and depressive-like behaviors in Itpr2-/- mice. Our results identify the previously unknown role of astrocyte dysfunction in driving rsFC abnormalities in depression.

Immunoglobulin Y Specific for SARS-CoV-2 Spike Protein Subunits Effectively Neutralizes SARS-CoV-2 Infectivity and Ameliorates Disease Manifestations In Vivo.

(Background) The coronavirus disease 2019 (COVID-19) that is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) carries high infectivity and mortality. Efficient intervention strategies are urgently needed. Avian immunoglobulin Y (IgY) showed efficacy against viral infection whereas the in vivo efficacy remains unclear. (Methods) We immunized laying hens with S1, S1 receptor-binding domain (S1-RBD), or S2 subunits of the SARS-CoV-2 spike (S) protein. After immunization, IgYs were collected and extracted from the egg yolks. The neutralization potential of IgYs was examined by the plaque reduction neutralization test (PRNT). The bioutility of IgYs was examined in Syrian hamsters in vivo. (Results) IgYs exhibited typical banding patterns in SDS-PAGE and Western blot and were immunoreactive against S1, S1-RBD, and S2 subunits. The plaque reduction neutralization test (PRNT) showed that all purified IgYs potently neutralized different SARS-CoV-2 strains in vitro. In Syrian hamsters, the combination of IgYs for S1-RBD and S2 subunits administered before or after SARS-CoV-2 infection effectively restored body weight loss and reduced intrapulmonary lesions and the amount of immunoreactive N protein-positive cells, which were caused by SARS-CoV-2 infection. (Conclusions) Collectively, IgYs specific for S protein subunits effectively neutralized SARS-CoV-2 in vitro and in vivo and may serve as prophylactic or therapeutic antibodies in the prevention or treatment of COVID-19.

Effects of the Short-Foot Exercise on Foot Alignment and Muscle Hypertrophy in Flatfoot Individuals: A Meta-Analysis.

This study aimed to conduct a meta-analysis of randomized controlled trials to examine the effects of the short-foot exercise (SFE) compared to foot orthosis or other types of interventions. Eligibility criteria involved participants with flatfoot engaging in the SFE compared to other forms of intervention or control groups without specific intervention. Relevant studies published before the end of June 2022 were identified from databases. A meta-analysis was performed by calculating the mean differences (MD) and standard MD (SMD) using the random effects model. Six trials with 201 patients (out of 609 records) that met selection criteria were reviewed. Five of the six trials implemented distinct interventions in the control group such as shoe insoles and muscle strengthening exercises, while in the remaining trial, controls received no intervention. The SFE group significantly reduced the navicular drop test (NDT) values (MD: -0.23; 95% confidence interval: -0.45 to -0.02; p = 0.04) and the foot posture index (FPI-6) score (MD: -0.67; 95% confidence interval: -0.98 to -0.36; p < 0.0001) when compared to the control group. The muscle hypertrophy did not differ significantly between the groups. The SFE may contribute more benefits than other intervention as it affects flatfoot individuals' foot alignment. Hence, the SFE is recommended as a beneficial dynamic support when facing flatfoot problems.

An observational study of acupuncture and complementary treatments for major depression: Case series from a preliminary study of proposed collaborative care model.

Background: Major depressive disorder is identified as a mood disorder characterized by episodically recurring and potentially life-threatening negative symptoms. It is currently important for study, as it involves high morbidity, mortality and prevalence, as well as unsatisfactory treatment results. Aim: Establish an outpatient model from an integrative approach promoting the diversified development of traditional Chinese and Western medicine cooperation, leading to a holistic intervention for patients with depression. Experimental procedure: Fifteen participants with moderate to severe depression were followed up for eight weeks in the Acupuncture Department of the China Medical University Hospital in Taichung, Taiwan, under a collaborative outpatient model that combined Western psychiatry and traditional Chinese medicine (TCM). Interdisciplinary Intervention included manual acupuncture twice a week (16 sessions), tai chi, yoga meditation, and nutritional assessment. Symptomatology was measured with primary outcomes (self-reporting via questionnaires) and secondary outcomes (heart rate variability [HRV] and blood samples to measure inflammation via high-sensitivity C-reactive protein [hs-CRP]). Results: The response rate was 80% (12/15 participants), with a statistically and clinically significant decrease in depression severity according to the 21-question Hamilton depression rating scale (HDRS21) (p < 0.001), the Beck Depression Inventory (BDI) (p < 0.003), and quality of life (QoL) questionnaires (p < 0.002). We found body constitution heterogeneity in the participants with major depressive disorder (MDD), predominantly blood stagnation and Qi stagnation (in 70% of participants). Conclusion: An interdisciplinary outpatient treatment method of complementary therapies can be applied successfully with pharmacological treatment in clinical practice to reduce depression symptomatology. Section: Physical/Mental practices. Taxonomy: Major Depressive Disorder, Collaborative healthcare Treatment, Observational study.

A booster dose of Delta × Omicron hybrid mRNA vaccine produced broadly neutralizing antibody against Omicron and other SARS-CoV-2 variants.

BACKGROUND: With the continuous emergence of new SARS-CoV-2 variants that feature increased transmission and immune escape, there is an urgent demand for a better vaccine design that will provide broader neutralizing efficacy. METHODS: We report an mRNA-based vaccine using an engineered "hybrid" receptor binding domain (RBD) that contains all 16 point-mutations shown in the currently prevailing Omicron and Delta variants. RESULTS: A booster dose of hybrid vaccine in mice previously immunized with wild-type RBD vaccine induced high titers of broadly neutralizing antibodies against all tested SARS-CoV-2 variants of concern (VOCs). In naïve mice, hybrid vaccine generated strong Omicron-specific neutralizing antibodies as well as low but significant titers against other VOCs. Hybrid vaccine also elicited CD8+/IFN-γ+ T cell responses against a conserved T cell epitope present in wild type and all VOCs. CONCLUSIONS: These results demonstrate that inclusion of different antigenic mutations from various SARS-CoV-2 variants is a feasible approach to develop cross-protective vaccines.

In Vivo Validation of Diffuse Optical Imaging with a Dual-Direction Measuring Module of Parallel-Plate Architecture for Breast Tumor Detection.

We demonstrate a working prototype of an optical breast imaging system involving parallel-plate architecture and a dual-direction scanning scheme designed in combination with a mammography machine; this system was validated in a pilot study to demonstrate its application in imaging healthy and malignant breasts in a clinical environment. The components and modules of the self-developed imaging system are demonstrated and explained, including its measuring architecture, scanning mechanism, and system calibration, and the reconstruction algorithm is presented. Additionally, the evaluation of feature indices that succinctly demonstrate the corresponding transmission measurements may provide insight into the existence of malignant tissue. Moreover, five cases are presented including one subject without disease (a control measure), one benign case, one suspected case, one invasive ductal carcinoma, and one positive case without follow-up treatment. A region-of-interest analysis demonstrated significant differences in absorption between healthy and malignant breasts, revealing the average contrast between the abnormalities and background tissue to exceed 1.4. Except for ringing artifacts, the average scattering property of the structure densities was 0.65-0.85 mm-1.

Glucocorticoid Receptor-Dependent Astrocytes Mediate Stress Vulnerability.

BACKGROUND: Major depressive disorder is a devastating psychiatric illness that affects approximately 17% of the population worldwide. Astrocyte dysfunction has been implicated in its pathophysiology. Traumatic experiences and stress contribute to the onset of major depressive disorder, but how astrocytes respond to stress is poorly understood. METHODS: Using Western blotting analysis, we identified that stress vulnerability was associated with reduced astrocytic glucocorticoid receptor (GR) expression in mouse models of depression. We further investigated the functions of astrocytic GRs in regulating depression and the underlying mechanisms by using a combination of behavioral studies, fiber photometry, biochemical experiments, and RNA sequencing methods. RESULTS: GRs in astrocytes were more sensitive to stress than those in neurons. GR absence in astrocytes induced depressive-like behaviors, whereas restoring astrocytic GR expression in the medial prefrontal cortex prevented the depressive-like phenotype. Furthermore, we found that GRs in the medial prefrontal cortex affected astrocytic Ca2+ activity and dynamic ATP (adenosine 5'-triphosphate) release in response to stress. RNA sequencing of astrocytes isolated from GR deletion mice identified the PI3K-Akt (phosphoinositide 3-kinase-Akt) signaling pathway, which was required for astrocytic GR-mediated ATP release. CONCLUSIONS: These findings reveal that astrocytic GRs play an important role in stress response and that reduced astrocytic GR expression in the stressed subject decreases ATP release to mediate stress vulnerability.

Predicting neuropsychiatric symptoms of persons with dementia in a day care center using a facial expression recognition system.

BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) affect 90% of persons with dementia (PwD), resulting in various adverse outcomes and aggravating care burdens among their caretakers. This study aimed to explore the potential of artificial intelligence-based facial expression recognition systems (FERS) in predicting BPSDs among PwD. METHODS: A hybrid of human labeling and a preconstructed deep learning model was used to differentiate basic facial expressions of individuals to predict the results of Neuropsychiatric Inventory (NPI) assessments by stepwise linear regression (LR), random forest (RF) with importance ranking, and ensemble method (EM) of equal importance, while the accuracy was determined by mean absolute error (MAE) and root-mean-square error (RMSE) methods. RESULTS: Twenty-three PwD from an adult day care center were enrolled with ≥ 11,500 FERS data series and 38 comparative NPI scores. The overall accuracy was 86% on facial expression recognition. Negative facial expressions and variance in emotional switches were important features of BPSDs. A strong positive correlation was identified in each model (EM: r = 0.834, LR: r = 0.821, RF: r = 0.798 by the patientwise method; EM: r = 0.891, LR: r = 0.870, RF: r = 0.886 by the MinimPy method), and EM exhibited the lowest MAE and RMSE. CONCLUSIONS: FERS successfully predicted the BPSD of PwD by negative emotions and the variance in emotional switches. This finding enables early detection and management of BPSDs, thus improving the quality of dementia care.

A new bioactive isocoumarin from the mangrove-derived fungus Penicillium sp. TGM112.

A new isocoumarin, penicimarin N (1), along with five known compounds (2-6), were isolated from the mangrove-derived fungus Penicillium sp. TGM112. The structure of 1 was elucidated on the basis of extensive spectroscopic data analysis, and the absolute configuration of 1 was determined by comparison of their circular dichroism (CD) spectra with the literature. The structures of known compounds were determined by comparison with the literature data. All the isolated compounds were examined for their antioxidant and α-glucosidase activities. Compound 1 showed strong antioxidant activity with the IC50 value of 1.0 mM, and 1 also exhibited moderate inhibitory activity against α-glucosidase with the IC50 value of 620 µM.

Longitudinal changes of frailty in 8 years: comparisons between physical frailty and frailty index.

BACKGROUND: Few studies have made longitudinal comparisons between frailty phenotype (FP) and frailty index (FI) changes. We aimed to investigate frailty status changes defined by FP and FI concurrently, and to compare the associated factors and incident disability among different combination of FI and FP trajectory groups. METHODS: Data on respondents aged over 50 who completed the 1999, 2003 and 2007 Taiwan Longitudinal Study on Aging (TLSA) surveys (n = 2807) were excerpted. Changes of FI, FP and major time-dependent variables were constructed by group-based trajectory modeling. Logistic regression was used to investigate the associated factors and relationships with incident disability among different frailty trajectories. RESULTS: We identified four FP trajectories - stably robust, worsened frailty, improved frailty, and stably frail and three FI trajectories - stable FI, moderate increase FI and rapid increase FI. Lower self-rated health, mobility impairment, and depressed mood were associated with unfavorable FP and FI changes (all p < 0.001). Regardless of FP trajectory groups, the moderate and rapid increase FI group had significantly more comorbidities than the stable FI group, and more visual, hearing, oral intake impairment, more difficulty in meeting living expenses, and poorer cognitive function in ≥65-year-olds (all p < 0.05). In addition, the worsened frailty, improved frailty, and stably frail groups had ORs for incident disability of 10.5, 3.0, and 13.4, respectively, compared with the stably robust group (all p < 0.01); the moderate and rapid increase FI groups had 8.4-fold and 77.5-fold higher risk than the stable FI group (both p < 0.001). When combining FI and FP trajectories, risk increased with FI trajectory steepness, independent of FP change (all p < 0.01 in rapid increase FI vs stable FI). CONCLUSIONS: Four FP trajectories (stably robust, worsened frailty, improved frailty, and stably frail) and three FI trajectories (stable FI, moderate increase FI and rapid increase FI) were identified. Lower self-rated health, mobility impairment, and depressed mood were associated with both unfavorable FP and FI trajectories. Nevertheless, even for individuals in stably robust or improved frailty FP groups, moderate or rapid increase in FI, either due to comorbidities, sensory impairment, cognitive deficits, or financial challenges, may still increase the risk of incident disability.

Toward instantaneous frequency of respiration to investigate the risk of internet gaming disorder.

With the development of Internet, the number of people with symptoms of Internet gaming disorder (IGD) has increased. In the past, psychologists used retrospective questionnaires to diagnose IGD. However, it is difficult to diagnose IGD symptoms instantaneously using retrospective questionnaires due to the requirement of an Internet gaming experience of greater than 6 months and the limitations of retrospective memory. Observing the physiological regulation system might instantaneously diagnose IGD. However, observation of instantaneous physiological response is limited due to the lack of appropriate techniques. Our previous study successfully combined complimentary ensemble empirical mode decomposition and normalized direct quadrature to obtain respiratory instantaneous frequency (IF) to overcome this limitation. This study uses game-related films as stimulus materials to observe the difference in respiratory IF response per second of gamers with high-risk IGD (HIGD) and low-risk IGD (LIGD). The result showed that the respiratory IF of gamers with HIGD is lower than those of gamers with LIGD at the time of stimulation. In addition, the study also observes the dynamic change in respiratory IF per second (IFdiff). The results showed that the instant at which a significant difference is observed in IFdiff between HIGD and LIGD can be matched to the stimulation of the films. In summary, this study demonstrated that the IFdiff of gamers with HIGD and LIGD are different when stimulated. Therefore, this suggests that IFdiff might be used as a potential physiological marker to instantaneously distinguish and diagnosis the risk of IGD.Clinical Relevance- This study investigates the dynamically psychophysiological response regulation by analyzing the respiratory IF of gamers diagnosed with IGD.

Influence of Chymosin on Physicochemical and Hydrolysis Characteristics of Casein Micelles and Individual Caseins.

The effects of chymosin on the physicochemical and hydrolysis characteristics of casein micelles and individual caseins were investigated. Adding 0.03 units of chymosin/mL led to the casein micelles in skim milk coagulating after a 3 h incubation period at 30 °C. SDS-PAGE investigation showed that ß-CN, κ-CN, αs-CN, and a portion of ß-lactoglobulin (ß-LG) in the milk supernatant fraction (MSF) were precipitated into the milk pellet fraction (MPF). The mean particle size of the MSF with chymosin decreased from 254.4 nm to 179.2 nm after a 3 h incubation period. Mass spectrometry and SDS-PAGE analysis suggested that chymosin hydrolyzed individual ß-CN, κ-CN, and αs-CN, but not ß-LG. Chymosin hydrolysis led to a decrease in the molecular weights of the hydrolyzed ß-CN, κ-CN, and αs-CN. Particle size analysis indicated that there was no difference in the particle size distribution of hydrolyzed ß-CN and αs-CN. Moreover, our outcomes demonstrated that the hydrolysis of κ-CN by chymosin occurs before that of ß-CN and αs-CN.