Gibberellins regulate masculinization through the SpGAI-SpSTM module in dioecious spinach.

The sex of dioecious plants is mainly determined by genetic factors, but it can also be converted by environmental cues such as exogenous phytohormones. Gibberellic acids (GAs) are well-known inducers of flowering and sexual development, yet the pathway of gibberellin-induced sex conversion in dioecious spinach (Spinacia oleracea L.) remains elusive. Based on sex detection before and after GA3 application using T11A and SSR19 molecular markers, we confirmed and elevated the masculinization effect of GA on a single female plant through exogenous applications of GA3, showing complete conversion and functional stamens. Silencing of GIBBERELLIC ACID INSENSITIVE (SpGAI), a single DELLA family protein that is a central GA signaling repressor, results in similar masculinization. We also show that SpGAI can physically interact with the spinach KNOX transcription factor SHOOT MERISTEMLESS (SpSTM), which is a homolog of the flower meristem identity regulator STM in Arabidopsis. The silencing of SpSTM also masculinized female flowers in spinach. Furthermore, SpSTM could directly bind the intron of SpPI to repress SpPI expression in developing female flowers. Overall, our results suggest that GA induces a female masculinization process through the SpGAI-SpSTM-SpPI regulatory module in spinach. These insights may help to clarify the molecular mechanism underlying the sex conversion system in dioecious plants while also elucidating the physiological basis for the generation of unisexual flowers so as to establish dioecy in plants.

Surf4 collaborates with derlin-2 and derlin-1 to mediate cyclooxygenase-2 translocation to the cytosol for degradation.

Derlin family members participate in the retrotranslocation of endoplasmic reticulum (ER) lumen proteins to the cytosol for ER-associated degradation (ERAD); however, the proteins facilitating this retrotranslocation remain to be explored. Using CRISPR library screening, we have found that derlin-2 and surfeit locus protein 4 (Surf4) are candidates to facilitate degradation of cyclooxygenase-2 (COX-2, also known as PTGS2). Our results show that derlin-2 acts upstream of derlin-1 and that Surf4 acts downstream of derlin-2 and derlin-1 to facilitate COX-2 degradation. Knockdown of derlin-2 or Surf4 impedes the ubiquitylation of COX-2 and the interaction of COX-2 with caveolin-1 (Cav-1) and p97 (also known as VCP) in the cytosol. Additionally, COX-2 degradation is N-glycosylation dependent. Although derlin-2 facilitates degradation of N-glycosylated COX-2, the interaction between derlin-2 and COX-2 is independent of COX-2 N-glycosylation. Derlin-1, Surf4 and p97 preferentially interact with non-glycosylated COX-2, whereas Cav-1 preferentially interacts with N-glycosylated COX-2, regardless of the N-glycosylation pattern. Collectively, our results reveal that Surf4 collaborates with derlin-2 and derlin-1 to mediate COX-2 translocation from the ER lumen to the cytosol. The derlin-2-derlin-1-Surf4-Cav-1 machinery might represent a unique pathway to accelerate COX-2 degradation in ERAD.

Recent Advances in Rechargeable Metal-CO2 Batteries with Nonaqueous Electrolytes.

This review article discusses the recent advances in rechargeable metal-CO2 batteries (MCBs), which include the Li, Na, K, Mg, and Al-based rechargeable CO2 batteries, mainly with nonaqueous electrolytes. MCBs capture CO2 during discharge by the CO2 reduction reaction and release it during charging by the CO2 evolution reaction. MCBs are recognized as one of the most sophisticated artificial modes for CO2 fixation by electrical energy generation. However, extensive research and substantial developments are required before MCBs appear as reliable, sustainable, and safe energy storage systems. The rechargeable MCBs suffer from the hindrances like huge charging-discharging overpotential and poor cyclability due to the incomplete decomposition and piling of the insulating and chemically stable compounds, mainly carbonates. Efficient cathode catalysts and a suitable architectural design of the cathode catalysts are essential to address this issue. Besides, electrolytes also play a vital role in safety, ionic transportation, stable solid-electrolyte interphase formation, gas dissolution, leakage, corrosion, operational voltage window, etc. The highly electrochemically active metals like Li, Na, and K anodes severely suffer from parasitic reactions and dendrite formation. Recent research works on the aforementioned secondary MCBs have been categorically reviewed here, portraying the latest findings on the key aspects governing secondary MCB performances.

Recurrent Occupational Hantavirus Infections Linked to Feeder Rodent Breeding Farm, Taiwan, 2022.

We investigated 2 acute cases and 1 previous case of Seoul hantavirus infection in workers in a feeder rodent breeding farm in Taiwan. Prevalence of hantavirus IgG among the tested feeder rats was 37.5%. Appropriate prevention measures, including using disinfection protocols and personal protective equipment, are crucial to lowering risk.

Increased Apolipoprotein A1 Expression Correlates with Tumor-Associated Neutrophils and T Lymphocytes in Upper Tract Urothelial Carcinoma.

An increased neutrophil-to-lymphocyte ratio (NLR) is a poor prognostic biomarker in various types of cancer, because it reflects the inhibition of lymphocytes in the circulation and tumors. In urologic cancers, upper tract urothelial carcinoma (UTUC) is known for its aggressive features and lack of T cell infiltration; however, the association between neutrophils and suppressed T lymphocytes in UTUC is largely unknown. In this study, we examined the relationship between UTUC-derived factors and tumor-associated neutrophils or T lymphocytes. The culture supernatant from UTUC tumor tissue modulated neutrophils to inhibit T cell proliferation. Among the dominant factors secreted by UTUC tumor tissue, apolipoprotein A1 (Apo-A1) exhibited a positive correlation with NLR. Moreover, tumor-infiltrating neutrophils were inversely correlated with tumor-infiltrating T cells. Elevated Apo-A1 levels in UTUC were also inversely associated with the population of tumor-infiltrating T cells. Our findings indicate that elevated Apo-A1 expression in UTUC correlates with tumor-associated neutrophils and T cells. This suggests a potential immunomodulatory effect on neutrophils and T cells within the tumor microenvironment, which may represent therapeutic targets for UTUC treatment.

Activation of STING by the novel liposomal TLC388 enhances the therapeutic response to anti-PD-1 antibodies in combination with radiotherapy.

Current immune checkpoint inhibiters (ICIs) have contrasting clinical results in poorly immunogenic cancers such as microsatellite-stable colorectal cancer (MSS-CRC). Therefore, understanding and developing the combinational therapeutics for ICI-unresponsive cancers is critical. Here, we demonstrated that the novel topoisomerase I inhibitor TLC388 can reshape the tumor immune landscape, corroborating their antitumor effects combined with radiotherapy as well as immunotherapy. We found that TLC388 significantly triggered cytosolic single-stranded DNA (ssDNA) accumulation for STING activation, leading to type I interferons (IFN-Is) production for increased cancer immunogenicity to enhance antitumor immunity. TLC388-treated tumors were infiltrated by a vast number of dendritic cells, immune cells, and costimulatory molecules, contributing to the favorable antitumor immune response within the tumor microenvironment. The infiltration of cytotoxic T and NK cells were more profoundly existed within tumors in combination with radiotherapy and ICIs, leading to superior therapeutic efficacy in poorly immunogenic MSS-CRC. Taken together, these results showed that the novel topoisomerase I inhibitor TLC388 increased cancer immunogenicity by ssDNA/STING-mediated IFN-I production, enhancing antitumor immunity for better therapeutic efficacy in combination with radiotherapy and ICIs for poorly immunogenic cancer.

Therapeutic efficacy of humanized monoclonal antibodies targeting dengue virus nonstructural protein 1 in the mouse model.

Dengue virus (DENV) which infects about 390 million people per year in tropical and subtropical areas manifests various disease symptoms, ranging from fever to life-threatening hemorrhage and even shock. To date, there is still no effective treatment for DENV disease, but only supportive care. DENV nonstructural protein 1 (NS1) has been shown to play a key role in disease pathogenesis. Recent studies have shown that anti-DENV NS1 antibody can provide disease protection by blocking the DENV-induced disruption of endothelial integrity. We previously demonstrated that anti-NS1 monoclonal antibody (mAb) protected mice from all four serotypes of DENV challenge. Here, we generated humanized anti-NS1 mAbs and transferred them to mice after DENV infection. The results showed that DENV-induced prolonged bleeding time and skin hemorrhage were reduced, even several days after DENV challenge. Mechanistic studies showed the ability of humanized anti-NS1 mAbs to inhibit NS1-induced vascular hyperpermeability and to elicit Fcγ-dependent complement-mediated cytolysis as well as antibody-dependent cellular cytotoxicity of cells infected with four serotypes of DENV. These results highlight humanized anti-NS1 mAb as a potential therapeutic agent in DENV infection.

Cardiac and renal outcomes of direct oral anticoagulants in patients with atrial fibrillation.

BACKGROUND: Oral anticoagulation therapy with warfarin or direct oral anticoagulants (DOACs) is the mainstay for stroke prevention in patients with non-valvular atrial fibrillation (AF). The DOACs might have a lower risk of declining renal function than warfarin. This study aimed to compare renal outcomes among rivaroxaban, edoxaban, dabigatran, and warfarin. METHOD: This cohort study identified 2203 adults with AF who started anticoagulation therapy between 1 July 2013 and 31 December 2020, in a clinical database at a single centre. Inverse probability of treatment weighting was adopted to balance baseline characteristics among four anticoagulants treatment groups. The primary outcome was a composite of cardiac and renal outcomes, involving a ≥30% decline in estimated glomerular filtration rate (eGFR), renal failure and cardiovascular death. RESULTS: After propensity score weighting, dabigatran was associated with significantly lower risks of a ≥30% decline in eGFR (hazard ratio [HR]: .69, 95% confidence interval [CI]: .497-.951, p = .0237), doubling of the serum creatinine level (HR: .49, 95% CI: .259-.927, p = .0282) and the cardiac and renal outcome composite (HR: .67, 95% CI: .485-.913, p = .0115) than warfarin. Rivaroxaban and edoxaban did not show significant protective effects on renal outcomes compared to warfarin. CONCLUSION: In this study, patients treated with dabigatran had significantly reduced risks of declining renal function and composite cardiac and renal events than those treated with warfarin. However, rivaroxaban and edoxaban were not associated with lower risks of any renal outcomes than warfarin. More studies are warranted to investigate and compare the impact of renal function between different DOACs in patients with AF.

Outcomes of different pulmonary rehabilitation protocols in patients under mechanical ventilation with difficult weaning: a retrospective cohort study.

BACKGROUND: The endeavor of liberating patients from ventilator dependence within respiratory care centers (RCCs) poses considerable challenges. Multiple factors contribute to this process, yet establishing an effective regimen for pulmonary rehabilitation (PR) remains uncertain. This retrospective study aimed to evaluate existing rehabilitation protocols, ascertain associations between clinical factors and patient outcomes, and explore the influence of these protocols on the outcomes of the patients to shape suitable rehabilitation programs. METHODS: Conducted at a medical center in northern Taiwan, the retrospective study examined 320 newly admitted RCC patients between January 1, 2015, and December 31, 2017. Each patient received a tailored PR protocol, following which researchers evaluated weaning rates, RCC survival, and 3-month survival as outcome variables. Analyses scrutinized differences in baseline characteristics and prognoses among three PR protocols: protocol 1 (routine care), protocol 2 (routine care plus breathing training), and protocol 3 (routine care plus breathing and limb muscle training). RESULTS: Among the patients, 28.75% followed protocol 1, 59.37% protocol 2, and 11.88% protocol 3. Variances in age, body-mass index, pneumonia diagnosis, do-not-resuscitate orders, Glasgow Coma Scale scores (≤ 14), and Acute Physiology and Chronic Health Evaluation II (APACHE) scores were notable across these protocols. Age, APACHE scores, and abnormal blood urea nitrogen levels (> 20 mg/dL) significantly correlated with outcomes-such as weaning, RCC survival, and 3-month survival. Elevated mean hemoglobin levels linked to increased weaning rates (p = 0.0065) and 3-month survival (p = 0.0102). Four adjusted models clarified the impact of rehabilitation protocols. Notably, the PR protocol 3 group exhibited significantly higher 3-month survival rates compared to protocol 1, with odds ratios (ORs) ranging from 3.87 to 3.97 across models. This association persisted when comparing with protocol 2, with ORs between 3.92 and 4.22. CONCLUSION: Our study showed that distinct PR protocols significantly affected the outcomes of ventilator-dependent patients within RCCs. The study underlines the importance of tailored rehabilitation programs and identifies key clinical factors influencing patient outcomes. Recommendations advocate prospective studies with larger cohorts to comprehensively assess PR effects on RCC patients.

Prevalence of swallowing disorder in different dementia subtypes among older adults: a meta-analysis.

BACKGROUND: Ageing process and abnormal protein accumulation in dementia damage neural pathways affecting the swallowing process and leading to swallowing disorder. OBJECTIVE: To estimate the prevalence of swallowing disorder among older adults with different dementia subtypes. METHODS: We conducted a systematic search across multiple databases, including PubMed, Embase, Scopus, Web of Science and OVID Medline. The meta-analysis employed R (version 4.0.2) and utilised a generalised linear mixed model with a random-effect approach to estimate the pooled prevalence of swallowing disorder among older adults, considering various dementia subtypes. The quality of included studies was assessed using Hoy's criteria. Heterogeneity was identified through Cochrane's Q and I2 statistics. To further explore heterogeneity, moderator analysis was performed to identify the contributing variables among the included studies. RESULTS: Eighteen studies with 12,532 older adults with different dementia subtypes were enrolled in our meta-analysis. The pooled prevalence of swallowing disorder among older adults with dementia was 58%, with 46.5% for Alzheimer's dementia, 34.9% for Parkinson's dementia, 18.8% for vascular dementia, 16.3% for mixed dementia and 12.2% for Lewy body dementia. According to assessment tools, Alzheimer's dementia had the highest prevalence, with 58% in instrumental assessments and 39% in clinical assessments. Medical history, Alzheimer's dementia, moderate-to-severe Clinical Dementia Rating, delayed oral phase, delayed pharyngeal phase and poor tongue motility contributed to the heterogeneity of the included studies. CONCLUSIONS: More than half of older adults with dementia demonstrate to have swallowing disorder. Our findings offer valuable insights to healthcare professionals for the identification of swallowing disorder in ageing population with dementia.

Effect of cervical Bishop score on induction of labor at term in primiparas using Foley catheter balloon: a retrospective study.

BACKGROUND: Previous studies had found that the mechanical methods were as effective as pharmacological methods in achieving vaginal delivery. However, whether balloon catheter induction is suitable for women with severe cervical immaturity and whether it will increase the related risks still need to be further explored. RESEARCH AIM: To evaluate the efficacy and safety of Foley catheter balloon for labor induction at term in primiparas with different cervical scores. METHODS: A total of 688 primiparas who received cervical ripening with a Foley catheter balloon were recruited in this study. They were divided into 2 groups: Group 1 (Bishop score ≤ 3) and Group 2 (3 < Bishop score < 7). Detailed medical data before and after using of balloon were faithfully recorded. RESULTS: The cervical Bishop scores of the two groups after catheter placement were all significantly higher than those before (Group 1: 5.49 ± 1.31 VS 2.83 ± 0.39, P<0.05; Group 2: 6.09 ± 1.00 VS 4.45 ± 0.59, P<0.05). The success rate of labor induction in group 2 was higher than that in group 1 (P<0.05). The incidence of intrauterine infection in Group 1 was higher than that in Group 2 (18.3% VS 11.3%, P<0.05). CONCLUSION: The success rates of induction of labor by Foley catheter balloon were different in primiparas with different cervical conditions, the failure rate of induction of labor and the incidence of intrauterine infection were higher in primiparas with severe cervical immaturity.

The application of the ICD-10 for antepartum stillbirth patients in a referral centre of Eastern China: a retrospective study from 2015 to 2022.

BACKGROUND: The causes of some stillbirths are unclear, and additional work must be done to investigate the risk factors for stillbirths. OBJECTIVE: To apply the International Classification of Disease-10 (ICD-10) for antepartum stillbirth at a referral center in eastern China. METHODS: Antepartum stillbirths were grouped according to the cause of death according to the International Classification of Disease-10 (ICD-10) criteria. The main maternal condition at the time of antepartum stillbirth was assigned to each patient. RESULTS: Antepartum stillbirths were mostly classified as fetal deaths of unspecified cause, antepartum hypoxia. Although more than half of the mothers were without an identified condition at the time of the antepartum stillbirth, where there was a maternal condition associated with perinatal death, maternal medical and surgical conditions and maternal complications during pregnancy were most common. Of all the stillbirths, 51.2% occurred between 28 and 37 weeks of gestation, the main causes of stillbirth at different gestational ages also differed. Autopsy and chromosomal microarray analysis (CMA) were recommended in all stillbirths, but only 3.6% received autopsy and 10.5% underwent chromosomal microarray analysis. CONCLUSIONS: The ICD-10 is helpful in classifying the causes of stillbirths, but more than half of the stillbirths in our study were unexplained; therefore, additional work must be done. And the ICD-10 score may need to be improved, such as by classifying stillbirths according to gestational age. Autopsy and CMA could help determine the cause of stillbirth, but the acceptance of these methods is currently low.

The expression profiles of cyp19a1, sf-1, esrs and gths in the brain-pituitary during gonadal sex differentiation in juvenile Japanese eels.

Eels are gonochoristic species whose gonadal differentiation initiates at the yellow eel stage and is influenced by environmental factors. We revealed some sex-related genes were sex dimorphically expressed in gonads during gonadal sex differentiation of Japanese eel (Anguilla japonica); however, the expression of sex-related genes in the brain-pituitary during gonadal sex differentiation in eels is still unclear. This study aimed to investigate the sex-related gene expressions in the brain-pituitary and tried to clarify their roles in the brain and gonads during gonadal sex differentiation. Based on our previous histological study, the control eels developed as males, and estradiol-17ß (E2) was used for feminization. Our results showed that during testicular differentiation, the brain cyp19a1 transcripts and aromatase proteins were increased significantly; moreover, the cyp19a1, sf-1, foxl2s, and esrs (except gperb) transcripts in the midbrain/pituitary also were increased significantly. Forebrain gnrh1 transcripts increased slightly during gonadal differentiation of both sexes, but the gnrhr1b and gnrhr2 transcripts in the midbrain/pituitary were stable during gonadal differentiation. The expression levels of gths and gh in the midbrain/pituitary were significantly increased during testicular differentiation and were much higher in males than in E2-feminized females. These results implied that endogenous estrogens might play essential roles in the brain/pituitary during testicular differentiation, sf-1, foxl2s, and esrs may have roles in cyp19a1 regulation in the midbrain/pituitary of Japanese eels. For the GnRH-GTH axis, gths, especially fshb, may be regulated by esrs and involved in regulating testicular differentiation and development in Japanese eels.

A Web-Based Resilience-Enhancing Program to Improve Resilience, Physical Activity, and Well-being in Geriatric Population: Randomized Controlled Trial.

BACKGROUND: Resilience is a protective factor in healthy aging, helping to maintain and recover physical and mental functions. The Resilience in Illness Model has proven effective in fostering resilience and well-being. Physical activity is crucial for older adults' independence and well-being, even as aging causes a progressive decline. Additionally, older adults face challenges such as spousal loss and physical disability, making preventive intervention strategies necessary. OBJECTIVE: This study aims to develop and evaluate a web-based program to enhance resilience, physical activity, and well-being among community-dwelling older adults. Additionally, we aim to gather feedback on the program's strengths and limitations. METHODS: A 4-week resilience-enhancing program was created, incorporating role-play and talk-in-interaction and focusing on 3 key skills: coping, control belief, and manageability. The program included scenarios such as becoming widowed and suffering a stroke, designed to engage older adults. A pilot test preceded the intervention. As a result of the COVID-19 pandemic, the program shifted from in-person to web-based sessions. A single-blind, parallel-group, randomized controlled trial was conducted. Participants aged over 65 years were recruited offline and randomly assigned to either an intervention or control group. A certified resilience practitioner delivered the program. Outcomes in resilience, physical activity, and well-being were self-assessed at baseline (T0), 4 weeks (T1), and 12 weeks (T2) after the program. A mixed methods approach was used to evaluate feedback. RESULTS: A web-based participatory program enhancing 3 skills-coping, control belief, and manageability for resilience-was well developed. Among 96 participants, 63 were randomized into the intervention group (n=31) and the control group (n=32). The mean age in the intervention group was 69.27 (SD 3.08) years and 74.84 (SD 6.23) years in the control group. Significant between-group differences at baseline were found in age (t45.6=-4.53, P<.001) and physical activity at baseline (t61=2.92, P=.005). No statistically significant between-group differences over time were observed in resilience (SE 7.49, 95% CI -10.74 to 18.61, P=.60), physical activity (SE 15.18, 95% CI -24.74 to 34.74, P=.74), and well-being (SE 3.74, 95% CI -2.68 to 11.98, P=.21) after controlling for baseline differences. The dropout rate was lower in the intervention group (2/31, 6%) compared with the control group (5/32, 16%). Moreover, 77% (24/31) of participants in the intervention group completed the entire program. Program feedback from the participants indicated high satisfaction with the web-based format and mentorship support. CONCLUSIONS: This study demonstrated that a web-based resilience-enhancing program is appropriate, acceptable, feasible, and engaging for community-dwelling older adults. The program garnered enthusiasm for its potential to optimize resilience, physical activity, and well-being, with mentorship playing a crucial role in its success. Future studies should aim to refine program content, engagement, and delivery methods to effectively promote healthy aging in this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT05808491; https://clinicaltrials.gov/ct2/show/NCT05808491.

Assessing the Clinical Effectiveness of an Exergame-Based Exercise Training Program Using Ring Fit Adventure to Prevent and Postpone Frailty and Sarcopenia Among Older Adults in Rural Long-Term Care Facilities: Randomized Controlled Trial.

BACKGROUND: Frailty and sarcopenia are geriatric syndromes of increasing concern and are associated with adverse health outcomes. They are more prevalent among long-term care facility (LTCF) users than among community dwellers. Exercise, especially multicomponent and progressive resistance training, is essential for managing these conditions. However, LTCFs, particularly in rural areas, face challenges in implementing structured exercise programs due to health care professional shortages. Moreover, older adults often become bored with repetitive exercise training and may lose interest over time. The Nintendo Switch Ring Fit Adventure (RFA) exergame is a novel exergame that combines resistance, aerobic, and balance exercises and offers a potential solution by boosting motivation in an immersive manner and reducing staff intervention needs. OBJECTIVE: We aimed to evaluate the clinical effectiveness of an exergame-based exercise training program delivered via RFA (exergame-RFA) in improving muscle mass and functional performance among older adult LTCF users. METHODS: This was a randomized controlled trial conducted from August 2022 to September 2023 and involved older adult LTCF users (aged ≥60 y) in rural southern Taiwan. Participants were randomized into an intervention group (exergame-RFA plus standard care) or a control group (standard care alone). The intervention, conducted seated with arm fit skills and trunk control exercises using the RFA, lasted 30 minutes twice weekly over 12 weeks. The primary outcomes measured were the Study of Osteoporotic Fractures index (serving as an indicator of frailty status) and the diagnostic criteria for sarcopenia (appendicular skeletal muscle mass index, handgrip strength, and gait speed). The secondary outcomes included functional performance (box and block test as well as maximum voluntary isometric contraction of the dominant upper extremity), muscle condition (muscle thickness measured using ultrasonography), activities of daily living (Kihon checklist), health-related quality of life (Short Form Health Survey-36), and cognitive function (brain health test). We used an intention-to-treat analysis, incorporating a simple imputation technique in statistical analysis. A mixed ANOVA, with time as a within-participant factor and intervention as a between-participant factor, was used to compare the training effects on outcomes. RESULTS: We recruited 96 individuals, of whom 60 (62%) underwent randomization. Of these 60 participants, 55 (92%) completed the study. Significant group×time interactions were observed in the intervention group in all primary outcomes (all P<.001, except P=.01 for handgrip strength) and most secondary outcomes, including maximum voluntary isometric contraction of the biceps (P=.004) and triceps brachii (P<.001) muscles, biceps muscle thickness measured using ultrasonography (P<.001), box and block test (P<.001), Kihon checklist (physical function: P=.01, mood status: P=.003, and total: P=.003), and brain health test (P<.001). CONCLUSIONS: The exergame-RFA intervention significantly improved muscle mass, strength, and functional performance among older adult users of rural LTCFs, offering a novel approach to addressing frailty and sarcopenia. TRIAL REGISTRATION: ClinicalTrials.gov NCT05360667; https://clinicaltrials.gov/study/NCT05360667. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.3389/fmed.2022.1071409.

Phenethyl isothiocyanate and irinotecan synergistically induce cell apoptosis in colon cancer HCT 116 cells in vitro.

Irinotecan (IRI), an anticancer drug to treat colon cancer patients, causes cytotoxic effects on normal cells. Phenethyl isothiocyanate (PEITC), rich in common cruciferous plants, has anticancer activities (induction of cell apoptosis) in many human cancer cells, including colon cancer cells. However, the anticancer effects of IRI combined with PEITC on human colon cancer cells in vitro were unavailable. Herein, the aim of this study is to focus on the apoptotic effects of the combination of IRI and PEITC on human colon cancer HCT 116 cells in vitro. Propidium iodide (PI) exclusion and Annexin V/PI staining assays showed that IRI combined with PEITC decreased viable cell number and induced higher cell apoptosis than that of IRI or PEITC only in HCT 116 cells. Moreover, combined treatment induced higher levels of reactive oxygen species (ROS) and Ca2+ than that of IRI or PEITC only. Cells pre-treated with N-acetyl-l-cysteine (scavenger of ROS) and then treated with IRI, PEITC, or IRI combined with PEITC showed increased viable cell numbers than that of IRI or PEITC only. IRI combined with PEITC increased higher caspase-3, -8, and -9 activities than that of IRI or PEITC only by flow cytometer assay. IRI combined with PEITC induced higher levels of ER stress-, mitochondria-, and caspase-associated proteins than that of IRI or PEITC treatment only in HCT 116 cells. Based on these observations, PEITC potentiates IRI anticancer activity by promoting cell apoptosis in the human colon HCT 116 cells. Thus, PEITC may be a potential enhancer for IRI in humans as an anticolon cancer drug in the future.

Allyl isothiocyanate induces DNA damage and inhibits DNA repair-associated proteins in a human gastric cancer cells in vitro.

Allyl isothiocyanate (AITC) is abundant in cruciferous vegetables and it present pharmacological activity including anticancer activity in many types of human cancer cells in vitro and in vivo. Currently, no available information to show AITC affecting DNA damage and repair-associated protein expression in human gastric cancer cells. Therefore, in the present studies, we investigated AITC-induced cytotoxic effects on human gastric cancer in AGS and SNU-1 cells whether or not via the induction of DNA damage and affected DNA damage and repair associated poteins expressions in vitro. Cell viability and morphological changes were assayed by flow cytometer and phase contrast microscopy, respectively, the results indicated AITC induced cell morphological changes and decreased total viable cells in AGS and SNU-1 cells in a dose-dependently. AITC induced DNA condensation and damage in a dose-dependently which based on the cell nuclei was stained by 4', 6-diamidino-2-phenylindole present in AGS and SNU-1 cells. DNA damage and repair associated proteins expression in AGS and SNU-1 cells were measured by Western blotting. The results indicated AITC decreased nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase-1 (HO-1), glutathione, and catalase, but increased superoxide dismutase (SOD (Cu/Zn)), and nitric oxide synthase (iNOS) in AGS cells, however, in SNU-1 cells are increased HO-1. AITC increased DNA-dependent protein kinase (DNA-PK), phosphorylation of gamma H2A histone family member X on Ser139 (γH2AXpSer139 ), and heat shock protein 90 (HSP90) in AGS cells. AITC increased DNA-PK, mediator of DNA damage checkpoint protein 1 (MDC1), γH2AXpSer139 , topoisomerase II alpha (TOPIIα), topoisomerase II beta (TOPIIß), HSP90, and heat shock protein 70 (HSP70) in SNU-1 cells. AITC increased p53, p53pSer15 , and p21 but decreased murine double minute 2 (MDM2)pSer166 and O6 -methylguanine-DNA methyltransferase (MGMT) in AGS cells; however, it has a similar effect of AITC except increased ataxia telangiectasia and Rad3 -related protein (ATR)pSer428 , checkpoint kinase 1 (CHK1), and checkpoint kinase 2 (CHK2) in SNU-1 cells. Apparently, both cell responses to AITC are different, nonetheless, all of these observations suggest that AITC inhibits the growth of gastric cancer cells may through induction off DNA damage in vitro.

Understanding Healthcare Providers' Care for Patients with Medications Treating Opioid Use Disorder in the Emergency Department: A Scoping Review.

BACKGROUND: There is limited research exploring the changing clinical practices among healthcare providers (HPs) care for patients with Emergency Department (ED)-initiated Medication for Opioid Use Disorder (MOUD). METHODS: This scoping review followed the methodological framework of Arksey and O'Malley to map relevant evidence and synthesize the findings. We searched PubMed, EMBASE, CINAHL, Web of Science, and Scopus for related studies from inception through October 12, 2022. Following the application of inclusion and exclusion criteria, 16 studies were included. Subsequently, they were charted and analyzed thematically based on ecological systems theory. RESULTS: The main determinants in the four ecological systems were generated as follows: (1) microsystem: willingness and attitude, professional competence, readiness, and preference; (2) mesosystem: ED clinical practices, departmental factors; (3) exosystem: multidisciplinary approaches, discharge planning, and (4) macrosystem: stigma, health insurance, policy. The findings have implications for HPs and researchers, as insufficient adoption, implementation, and retention of MOUD in the ED affect clinical practices. CONCLUSIONS: Across the four ecological systems, ED-initiated MOUD is shaped by multifaceted determinants. The microsystem underscores pivotal patient-HP trust dynamics, while the mesosystem emphasizes interdepartmental synergies. Exosystemically, resource allocation and standardized training remain paramount. The macrosystem reveals profound effects of stigma, insurance disparities, and evolving policies on treatment access and efficacy. Addressing these interconnected barriers is crucial for optimizing patient outcomes in the context of MOUD.

Melanocyte transplantation to skin prepared by controlled PUVA-induced sunburn-like blistering for vitiligo treatment - A pilot clinical trial.

Vitiligo is a common acquired disease of pigment loss. In lesions recalcitrant to non-invasive treatment, transplantation of cultured autologous melanocytes is an emerging choice. Conventionally, the recipient site is often prepared by laser-mediated or mechanical dermabrasion. Such preparation procedures have disadvantages including prolonged transplantation duration, long period for reepithelialization and potential scarring. We propose a method of preparing recipient sites by psoralen and controlled ultraviolet A (PUVA)-induced blistering followed by transplanting suspended melanocytes. We introduced this method in 10 patients with segmental vitiligo on their recipient site 3 to 5 days before transplantation and blistering developed in 2 to 3 days afterwards. On the day of transplantation, the blister roof could be peeled off easily without bleeding and the recipient site preparation could be completed in 20 min. The recipient site became reepithelialized within 1 week. Progressive repigmentation was observed for up to 6 months, with an average of 65.06% repigmentation in the recipient site without scarring at the end of follow-up. Hence, preparation of the recipient site by controlled PUVA-induced sunburn-like blistering can potentially facilitate melanocyte transplantation and prevent scarring.

Data-Fusion-Based Quality Enhancement for HR Measurements Collected by Wearable Sensors.

The advancements of Internet of Things (IoT) technologies have enabled the implementation of smart and wearable sensors, which can be employed to provide older adults with affordable and accessible continuous biophysiological status monitoring. The quality of such monitoring data, however, is unsatisfactory due to excessive noise induced by various disturbances, such as motion artifacts. Existing methods take advantage of summary statistics, such as mean or median values, for denoising, without taking into account the biophysiological patterns embedded in data. In this research, a functional data analysis modeling method was proposed to enhance the data quality by learning individual subjects' diurnal heart rate (HR) patterns from historical data, which were further improved by fusing newly collected data. This proposed data-fusion approach was developed based on a Bayesian inference framework. Its effectiveness was demonstrated in an HR analysis from a prospective study involving older adults residing in assisted living or home settings. The results indicate that it is imperative to conduct personalized healthcare by estimating individualized HR patterns. Furthermore, the proposed calibration method provides a more accurate (smaller mean errors) and more precise (smaller error standard deviations) HR estimation than raw HR and conventional methods, such as the mean.