Efficacy of Traditional Acupuncture Compared to Biofeedback Therapy in Fecal Incontinence: A Randomized Controlled Trial.

BACKGROUND: Fecal incontinence has a devastating impact on quality of life and imposes a substantial socioeconomic burden. Best medical therapy including biofeedback therapy improves mild symptoms, with minimal impact on moderate to severe symptoms. Surgical management for incontinence carries a degree of morbidity resulting in low uptake and acceptability. While acupuncture is common practice in Singapore for numerous medical conditions, its role in fecal incontinence is relatively novel. In our local context, however, acupuncture is accessible, inexpensive, and potentially well-accepted as a treatment strategy. OBJECTIVE: To determine the effectiveness of Traditional Chinese Medicine acupuncture, compared to biofeedback therapy in the treatment of fecal incontinence. The secondary aim is to investigate the differences in quality of life following treatment. DESIGN: Randomized controlled trial. SETTING: Prospective, single institution study. PATIENTS: Patients with ≥2 episodes of fecal incontinence/week, or St Mark's incontinence score of ≥5 were recruited. Patients were randomized into biofeedback therapy which included 3 sessions over 10 weeks, or 30 sessions of acupuncture over 10 weeks. MAIN OUTCOME MEASURES: Incontinence episodes, St. Mark's Score and Fecal Incontinence Quality of Life scale. RESULTS: Eighty-five patients were randomized into biofeedback therapy (n=46) or acupuncture (n = 39). Demographics and baseline clinical characteristics were not different (p > 0.05). Overall median incontinence episodes were reduced in both, with the acupuncture arm reporting significantly fewer at week 15 (p < 0.001). Acupuncture also improved quality of life, with improvement in lifestyle, coping, depression, and embarrassment at week 15 (p < 0.05). While the St. Mark's score was significantly reduced in both arms at week 15 (p < 0.001), the acupuncture arm's score was significantly lower (p = 0.002). LIMITATIONS: Longer follow-up required. CONCLUSIONS: Acupuncture is clinically effective and improves quality of life in patients with fecal incontinence. See Video Abstract. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov: NCT04276350.

Subcellular localization of viral proteins after porcine epidemic diarrhea virus infection and their roles in the viral life cycle.

Porcine epidemic diarrhea virus (PEDV) is one of the most devastating diseases affecting the pig industry globally. Due to the emergence of novel strains, no effective vaccines are available for prevention and control. Investigating the pathogenic mechanisms of PEDV may provide insights for creating clinical interventions. This study constructed and expressed eukaryotic expression vectors containing PEDV proteins (except NSP11) with a 3' HA tag in Vero cells. The subcellular localization of PEDV proteins was examined using endogenous protein antibodies to investigate their involvement in the viral life cycle, including endocytosis, intracellular trafficking, genome replication, energy metabolism, budding, and release. We systematically analyzed the potential roles of all PEDV viral proteins in the virus life cycle. We found that the endosome sorting complex required for transport (ESCRT) machinery may be involved in the replication and budding processes of PEDV. Our study provides insight into the molecular mechanisms underlying PEDV infection. IMPORTANCE: The global swine industry has suffered immense losses due to the spread of PEDV. Currently, there are no effective vaccines available for clinical protection. Exploring the pathogenic mechanisms of PEDV may provide valuable insights for clinical interventions. This study investigated the involvement of viral proteins in various stages of the PEDV lifecycle in the state of viral infection and identified several previously unreported interactions between viral and host proteins. These findings contribute to a better understanding of the pathogenic mechanisms underlying PEDV infection and may serve as a basis for further research and development of therapeutic strategies.

Effects of fresh-salt water interaction on spatial variations of soil organic carbon in reed wetland of Yellow River Estuary.

Estuarine wetlands exhibit significant interaction between fresh and salt water, with long-term carbon sequestration capability. We set up 60 sampling sites in the reed wetlands of the fresh-salt water interaction zone of the Yellow River Estuary, covering four different zones of the weak-intensity fresh-salt water interaction zone (WIZ), medium-intensity fresh-salt water interaction zone (MIZ), high-intensity interaction fresh-salt water zone (HIZ) and strong-intensity fresh-salt water interaction zone (SIZ). We investigated how fresh-salt water interaction affected the spatial variation of soil organic carbon (SOC) storage. The results showed that the area of reed wetland accounted for 17.8% of the total area of the fresh-salt water interaction zone the Yellow River Estuary, which mainly distributed in the WIZ and MIZ. The SOC content of reed wetland in the fresh-salt water interaction zone ranged from 1.09 to 3.65 g·kg-1, the SOC density was between 1.85-5.84 kg·m-2, and the SOC storage was (17.32±3.64)×104 t. The SOC content and SOC density decreased with increasing fresh-salt water interaction. There were significant differences in surface SOC content between different subzones of the fresh-salt water interaction zone. The surface SOC content decreased significantly with the increases of fresh-salt water interaction intensity. SOC density was positively correlated with SOC, TN, NH4+-N, and biomass, but negatively correlated with salt ions, soil bulk density, pH, and EC. SOC storage in the 0-30 cm soil layer accounted for 50.9%-64.2% of that in the 0-60 cm soil layer, while SOC storage in the 0-60 cm soil layer occupied 19.1%-37.7% of that in the 0-400 cm soil layer. The results could provide a scientific basis for accurately evaluating SOC storage of estuarine wetlands, improving carbon sink function and wetland management.

The emotional impact of uncomplicated urinary tract infections in women in China and Japan: a qualitative study.

BACKGROUND: Uncomplicated urinary tract infections (uUTIs) are one of the most common community-acquired infections, particularly among women. Common symptoms of UTI include dysuria, urinary urgency and increased frequency, and lower abdominal pain. With appropriate treatment, symptoms may resolve in a few days. However, there is a lack of research on the emotional impact of this disease. We conducted a qualitative, interview-based study to gain a greater understanding of the emotional impact of uUTIs in women in China and Japan. METHODS: A qualitative, exploratory, in-depth, interview-based study was conducted between 19 November 2020 and 25 February 2021. Women aged ≥ 18 years who experienced ≥ 1 uUTI and received antibiotic treatment in the past year were eligible for inclusion. Participants must have experienced ≥ 1 of the following symptoms during a uUTI episode: urinary urgency, frequency, dysuria, or lower abdominal/suprapubic pain. Participants who reported back pain or fever (indicative of complicated UTI) were excluded. Participants with recurrent or sporadic UTIs were included, with specific screening criteria used to ensure capture of both groups. Following a screening call, a structured, in-depth telephone interview (~ 30 min in duration) was conducted by three female external moderators trained in qualitative interviewing, assisted by an interview guide. Interviews were analysed individually and thematically, with the results presented within the identified themes. RESULTS: A total of 65 women with uUTI completed the in-depth telephone interview: 40 (62%) from China and 25 (38%) from Japan. Participants reported that the symptoms of uUTI affected multiple aspects of their lives, and described feelings of embarrassment, frustration, guilt, dread, and loneliness associated with symptoms that interfered with relationships, work and daily activities, and sleep. Participants reported seeking healthcare from several different points of contact, from local pharmacies to hospitals. CONCLUSIONS: Our analysis highlights the profound emotional impact of uUTIs in women in China and Japan, and the journey these participants take before their initial interaction with a healthcare professional. These insights emphasise the need to better understand the full impact of uUTI, and the role of healthcare professionals in improved patient education and support.

Clinical study of electroacupuncture combined with exercise therapy in improving the balance function of patients with knee osteoarthritis / 针灸推拿医学（英文版）

Objective:To observe the clinical effect of electroacupuncture(EA)combined with exercise therapy on balance function in patients with knee osteoarthritis(KOA). Methods:Seventy patients with KOA were randomly divided into a treatment group and a control group,with 35 cases in each group.The treatment group was treated with EA combined with exercise therapy.EA was applied to Dubi(ST35),Neixiyan(EX-LE4),Xuehai(SP10),Liangqiu(ST34),Yanglingquan(GB34),and Zusanli(ST 36).Exercise therapy(muscle strength training and knee mobility training)was applied after EA.The control group only received the same exercise therapy as the treatment group.The two groups were treated with the same course of treatment,3 times a week for 4 consecutive weeks,12 times in total,and followed up for 1 month.The Pro-Kin254P balance test system was used to measure the balance function parameters at 4 time points,including before treatment,after 1 session of treatment,after 12 sessions of treatment,and at 1-month follow-up after treatment.The visual analog scale(VAS)and the Western Ontario and McMaster Universities osteoarthritis index(WOMAC)scores were recorded. Results:The markedly effective rate and total effective rate in the treatment group were higher than those in the control group(P<0.01).The Romberg area,Romberg length,and VAS scores of the two groups decreased significantly after 1 session of treatment,12 sessions of treatment,and 1 month after treatment,and the differences between different time points in the same group were statistically significant(P<0.01).There were significant differences between the two groups at the same time point(P<0.05).The total WOMAC scores of the two groups after 1 session of treatment,12 sessions of treatment,and 1 month after treatment decreased significantly,and there were significant differences between different time points in the same group(P<0.05),but there was no significant difference between the two groups at the same time point(P>0.05). Conclusion:EA combined with exercise therapy or exercise therapy alone can enhance the balance function,relieve joint pain,and improve joint function in patients with KOA.EA combined with exercise therapy is superior to exercise therapy alone in improving balance function and pain,but the two treatment protocols have similar effects in improving joint function.

The role of C-reactive protein to prealbumin ratio for diagnosis and prognosis evaluation of sepsis / 中国医师进修杂志

Objective:To explore the application of C-reactive protein(CRP) to prealbumin (PA) ratio(CRP/PA) for diagnosis and prognosis evaluation of sepsis.Methods:By a retrospective study, a total of 95 sepsis patients (sepsis group) and 100 local infection patients(non-sepsis group) treated in Dongying People′s Hospital from September 2021 to September 2022 were enrolled. Sepsis patients were divided into survival group(57 cases) and death group (38 cases) according to the 28-day outcome. The clinical data were collected and CRP/PA was calculated. Multivariate Logistic regression and Cox regression were used to analyze the relationship between various indicators and the occurrence and prognosis of sepsis, and receiver operating characteristic (ROC) curve was drawn to evaluate the diagnostic and prognostic value of CRP/PA for sepsis. Kaplan-Meier survival analysis was used to evaluate the prognostic value of different CRP/PA ratios for patients with sepsis.Results:The systolic blood pressure, diastolic blood pressure, prealbumin were lower and heart rate, respiratory rate, CRP, CRP/PA, procalcitonin were higher in the sepsis group compared to the non-sepsis group: (117.27 ± 11.65) mmHg (1 mmHg = 0.133 kPa) vs. (123.26 ± 10.71) mmHg, (69.42 ± 8.58) mmHg vs. (75.44 ± 6.53) mmHg, (174.09 ± 24.77) g/L vs. (207.13 ± 34.31) g/L, (97.87 ± 12.73) bpm vs. (86.90 ± 10.19) bpm, 22.0(20.00, 25.00) times/min vs. 21.00(19.00, 23.00) times/min, (93.96 ± 19.64) mg/L vs. (77.56 ± 22.54) mg/L, 0.54(0.44, 0.65) vs. 0.37(0.28, 0.46), 3.35(2.16, 4.17) μg/L vs. 1.52(0.81, 2.16) μg/L, there were statistical differences ( P<0.05). Multivariate Logistic regression analysis showed that CRP/PA and procalcitonin were risk factors for sepsis ( P<0.05). The results of ROC curve showed that the area under the curve (AUC) of CRP/PA in diagnosis of sepsis was 0.821, the specificity and sensitivity was 76.0% and 93.7%, respectively. The diastolic blood pressure, prealbumin, neutrophil were higher and the heart rate, respiratory rate, CRP, CRP/PA, lymphocytes, procalcitonin were lower in the survival group compared to the death group: (71.76 ± 8.86) mmHg vs. (67.86 ± 8.10) mmHg, (181.46 ± 24.35) g/L vs. (163.05 ± 21.28) g/L, (63.46 ± 9.88) × 10 9/L vs.(57.13 ± 8.64) × 10 9/L, (95.68 ± 13.48) times/min vs. (101.16 ± 10.88) times/min, 22.00(19.50, 24.00) times/min vs. 24.00(20.00, 28.00) times/min, (88.09 ± 19.35) mg/L vs. (102.76 ± 16.75) mg/L, 0.46(0.41, 0.58) vs. 0.63(0.55, 0.72), 21.00(16.00, 30.00) ×10 9/L vs. 29.50(18.00, 37.30) ×10 9/L, 2.94(2.10, 3.97) μg/L vs. 3.82(2.21, 4.77) μg/L, there were statistical differences ( P<0.05). Multivariate Cox regression analysis showed that CRP/PA and procalcitonin were independent risk factors for the prognosis of sepsis ( P<0.05). The AUC of CRP/PA in predicting the prognosis of sepsis was 0.827, the specificity and sensitivity was 92.1% and 63.8%, respectively. Grouped by the cut-off of CRP/PA (0.48), the 28-day mortality rate of patients in the CRP/PA>0.48 was significantly higher than that of patients in the CRP/PA≤0.48, there was statistical difference ( P<0.01). Conclusions:CRP/PA ratio can be used as an index for diagnosis and prognosis evaluation of sepsis.

Exploring the adaptive leisure activities of classified nursing model in elderly colon cancer patients: a perspective on interactive care.

OBJECTIVE: The aims of the study were first to explore the adaptive leisure activities of classified nursing model from the perspective of nurse-patient interactive care, and to explore its impact on the physical and mental health of patients with colon cancer. METHODS: From September 2017 to March 2022 as the observation time node, 82 patients with colon cancer who met the established inclusion and exclusion criteria were regarded as the research objects through the random number table as the grouping tool. The two groups of patients were named as the research group and the control group, with 41 patients in each group. The control group implemented routine nursing measures, and the research group implemented classified nursing mode and adaptive leisure activity mode. The two groups of patients received 4 weeks of nursing intervention. With the help of self-rating anxiety scale, self-rating depression scale, self-care ability evaluation scale and health status survey brief form, the two groups of patients were compared before intervention and at the end of the 4th week after intervention. RESULTS: After the intervention, the anxiety score (t = 6.656, p < 0.001) and depression score (t = 4.851, p < 0.001) of the research group were lower than those of the control group, and the difference was statistically significant. After the intervention, the self-concept (t = 4.845, p < 0.001), self-responsibility (t = 6.071, p < 0.001), self-care skills (t = 3.341, p < 0.001), health knowledge (t = 3.698, p < 0.001) and total score (t = 9.246, p < 0.001) of the research group were higher than those of the control group, and the difference was statistically significant. After the intervention, physical functioning (t = 8.141, p < 0.001), bodily pain (t = 6.083, p < 0.001), general health (t = 9.424, p < 0.001), role-physical (t = 8.057, p < 0.001), role-emotional (t = 13.252, p < 0.001), mental health (t = 12.565, p < 0.001), social functioning (t = 10.813, p < 0.001) and vitality score (t = 12.890, p < 0.001) of the research group were higher than those of the control group, with significant differences. CONCLUSION: Interactive care through adaptive leisure nursing improves mental well-being, self-management, and psychosocial functioning in elderly colon cancer patients, promoting overall health.

Enantioselective Reductive Cross-Couplings of Olefins by Merging Electrochemistry with Nickel Catalysis.

The merger of electrochemistry and transition metal catalysis has emerged as a powerful tool to join two electrophiles in an enantioselective manner. However, the development of enantioselective electroreductive cross-couplings of olefins remains a challenge. Inspired by the advantages of the synergistic use of electrochemistry with nickel catalysis, we present here a Ni-catalyzed enantioselective electroreductive cross-coupling of acrylates with aryl halides and alkyl bromides, which affords chiral α-aryl carbonyls in good to excellent enantioselectivity. Additionally, this catalytic reaction can be applied to (hetero)aryl chlorides, which is difficult to achieve by other methods. The combination of cyclic voltammetry analysis with electrode potential studies suggests that the NiI species activates aryl halides by oxidative addition and alkyl bromides by single-electron transfer.

[Effects of Water-salt Environment on Freshwater Wetland Soil C, N, and P Ecological Stoichiometric Characteristics in the Yellow River Estuary Wetland].

Carbon (C), nitrogen (N), and phosphorus (P) are important nutrients, and their ecological stoichiometric characteristics can reflect the quality and fertility capacity of soil, which is critical to understanding the stable mechanisms of estuarine wetland ecosystems. Under global changes, the increase in salinity and flooding caused by sea level rise will lead to changes in biogeochemical processes in estuarine wetlands, which is expected to affect the ecological stoichiometric characteristics of soil C, N, and P and ultimately interfere with the stability of wetland ecosystems. However, it remains unclear how the C, N, and P ecological stoichiometric characteristics respond to the water-salt environment in estuarine wetlands. We differentiated changes in the C, N, and P ecological stoichiometric characteristics through an ex-situ culture experiment for 23 months in the Yellow River Estuary Wetland. The five sites with distinct tidal hydrology were selected to manipulate translocation of soil cores from the freshwater marsh to high-, middle-, and low-tidal flats in June 2019. The results showed that soil water content (SWC); electrical conductivity (EC); and C, N, and P ecological stoichiometric characteristics of freshwater marsh soil significantly changed after translocation for 23 months. SWC decreased on the high- and middle-tidal flats (P<0.05) and increased on the low-tidal flat (P<0.05). EC increased to different degrees on all three tidal flats (P<0.05). Soil total organic carbon (TOC) and total nitrogen (TN) were significantly lower on the high-tidal flat (P<0.05), whereas total phosphorus (TP) was significantly lower on the middle- and high-tidal flats (P<0.05). C:N was decreased on the high- and middle-tidal flats (P<0.05); C:P and N:P were lower on the high-tidal flat; and all C, N, and P ecological stoichiometric characteristics showed no change on the low-tidal flat (P>0.05). Pearson's analysis showed that the ecological stoichiometric characteristics of C, N, and P were related to some properties of soil over the culture sites. The PLS-SEM model showed that the water-salt environment had different effects on soil C:N, C:P, and N:P through the main pathways of negative effects on soil TOC and TP. The results suggest that sea level rise may impact the C, N, and P ecological stoichiometric characteristics in freshwater marsh soil, resulting in some possible changes in the nutrient cycles of estuarine wetlands.

Mediating effect of physical sub-health in the association of sugar-sweetened beverages consumption with depressive symptoms in Chinese college students: A structural equation model.

BACKGROUND: Although previous findings with small samples indicated that sugar-sweetened beverages (SSB) consumption was associated with depressive symptoms in adolescents, the mediating effect of physical sub-health in the association is unknown. METHODS: A survey was conducted among freshmen from 11 provinces in China. A food frequency questionnaire was used to collect dietary behavior, and patient health questionnaire-9 items was used to assess depressive symptoms. A generalized linear model was used to analyze the association between SSB consumption, physical sub-health and depressive symptoms. The structural equation model was used to analyze the mediating effect of physical sub-health. RESULTS: Of the 31,856 participants, 36.5 % had positive depressive symptoms. After adjusting for variables, carbonate beverages (ß = 0.11; 95%CI: 0.07-0.15; P = 0.000) and milk tea (ß = 0.07; 95%CI: 0.01-0.13; P = 0.021) consumption was associated with depressive symptoms in boys. Carbonate beverages (ß = 0.09; 95%CI: 0.05-0.13; P = 0.000), tea beverages (ß = 0.09; 95%CI: 0.04-0.13; P = 0.000), and milk tea (ß = 0.08; 95%CI: 0.04-0.11; P = 0.000) consumption was associated with depressive symptoms in girls. The mediating effect of physical sub-health accounted for 81.3 % of the total effect in the mediating model of SSB associated with depressive symptoms. LIMITATIONS: Retrospective survey has certain information bias. Association observed in the cross-sectional study is uncertain. CONCLUSIONS: The present study suggests that the consumption of SSB associated with depressive symptoms in Chinese college students, and physical sub-health plays a complete mediating role in the association.

Correction: Deng et al. Distinct Roles of Ena ATP Family Proteins in Sodium Accumulation, Invasive Growth, and Full Virulence in Colletotrichum gloeosporioides. J. Fungi 2023, 9, 566.

In the original publication [...].

Parallel paired electrolysis-enabled asymmetric catalysis: simultaneous synthesis of aldehydes/aryl bromides and chiral alcohols.

Metal-catalyzed asymmetric electro-reductive couplings have emerged as a powerful tool for organic synthesis, wherein a sacrificial anode is typically required. Herein, a parallel paired electrolysis (PPE)-enabled asymmetric catalysis has been developed, and the alcohols and ketones could be simultaneously converted to the corresponding aldehydes and chiral tertiary alcohols with high yields and enantioselectivity in an undivided cell. Additionally, this Ni-catalyzed asymmetric reductive coupling can well match the anodic oxidative C-H bond bromination of (hetero)arenes. This protocol opens an alternative avenue for organic synthesis.

Distinct Roles of Ena ATP Family Proteins in Sodium Accumulation, Invasive Growth, and Full Virulence in Colletotrichum gloeosporioides.

Colletotrichum gloeosporioides, a significant fungal pathogen of crops and trees, causes large economic losses worldwide. However, its pathogenic mechanism remains totally unclear. In this study, four Ena ATPases (Exitus natru-type adenosine triphosphatases), homology of yeast Ena proteins, were identified in C. gloeosporioides. Gene deletion mutants of ΔCgena1, ΔCgena2, ΔCgena3, and ΔCgena4 were obtained through the method of gene replacement. First, a subcellular localization pattern indicated that CgEna1 and CgEna4 were localized in the plasma membrane, while the CgEna2 and CgEna3 were distributed in the endoparasitic reticulum. Next, it was found that CgEna1 and CgEna4 were required for sodium accumulation in C. gloeosporioides. CgEna3 was required for extracellular ion stress of sodium and potassium. CgEna1 and CgEna3 were involved in conidial germination, appressorium formation, invasive hyphal development, and full virulence. The mutant of ΔCgena4 was more sensitive to the conditions of high concentrations of ion and the alkaline. Together, these results indicated that CgEna ATPase proteins have distinct roles in sodium accumulation, stress resistance, and full virulence in C. gloeosporioides.

Case report: Acne vulgaris treatment with 5-Aminolaevulinic acid photodynamic therapy and adalimumab: a novel approach.

Acne vulgaris is a common skin condition that affects a large proportion of teenagers and young adults. Despite the availability of various treatment options, many patients experience inadequate relief or intolerable side effects. Photodynamic therapy (PDT) is a growing interest in the treatment of acne vulgaris, with 5-Aminolaevulinic acid (ALA) being one of the most commonly used photosensitizers. Adalimumab is a biologic medication used to treat inflammatory skin conditions such as Psoriasis and Hidradenitis suppurativa (HS), which targets TNF-α. Combining different therapies, such as ALA-PDT and adalimumab, can often provide more effective and longer-lasting results. This report presents the case of a patient with severe and refractory acne vulgaris who was treated with a combination of ALA-PDT and adalimumab, resulting in significant improvement in the condition. The literature review highlights the significant comorbidity associated with acne, emphasizing the need for potential of TNF-α inhibitors for its effective treatments that address physical symptoms and ALA-PDT is known to treat scar hyperplasia, and to prevent or minimize the formation of post-acne hypertrophic scars. The combination of TNF inhibitors and ALA-PDT or adalimumab has shown promising results in treating inflammatory skin conditions, including severe and refractory acne vulgaris, as per recent studies.

High-power, multi-junction, 905†nm vertical-cavity surface-emitting laser with an AlGaAsSb electron-blocking layer.

We report high-power multi-junction vertical-cavity surface-emitting lasers (VCSELs) with a significantly suppressed carrier leakage issue under high injection current and temperature. By carefully optimizing the energy band structure of quaternary AlGaAsSb, we obtained a 12-nm-thick AlGaAsSb electron-blocking layer (EBL) with a high effective barrier height (∼122 meV), a low compressive strain (∼0.99%), and a reduced electronic leakage current. The resulting three-junction (3J) 905 nm VCSEL with the proposed EBL exhibits an improved maximum output power (∼46.4 mW) and power conversion efficiency (PCE; ∼55.4%) during room-temperature operation. Also, it was found from thermal simulation that the optimized device shows more advantages over the original device during high-temperature operation. The type-II AlGaAsSb EBL provided an excellent electron-blocking effect and would be a promising strategy for multi-junction VCSELs to realize high-power applications.

Nickel/biimidazole-catalyzed electrochemical enantioselective reductive cross-coupling of aryl aziridines with aryl iodides.

Here, we report an asymmetric electrochemical organonickel-catalyzed reductive cross-coupling of aryl aziridines with aryl iodides in an undivided cell, affording ß-phenethylamines in good to excellent enantioselectivity with broad functional group tolerance. The combination of cyclic voltammetry analysis of the catalyst reduction potential as well as an electrode potential study provides a convenient route for reaction optimization. Overall, the high efficiency of this method is credited to the electroreduction-mediated turnover of the nickel catalyst instead of a metal reductant-mediated turnover. Mechanistic studies suggest a radical pathway is involved in the ring opening of aziridines. The statistical analysis serves to compare the different design requirements for photochemically and electrochemically mediated reactions under this type of mechanistic manifold.

Porcine Enteric Alphacoronavirus Entry through Multiple Pathways (Caveolae, Clathrin, and Macropinocytosis) Requires Rab GTPases for Endosomal Transport.

Porcine enteric alphacoronavirus (PEAV) is a new bat HKU2-like porcine coronavirus, and its endemic outbreak has caused severe economic losses to the pig industry. Its broad cellular tropism suggests a potential risk of cross-species transmission. A limited understanding of PEAV entry mechanisms may hinder a rapid response to potential outbreaks. This study analyzed PEAV entry events using chemical inhibitors, RNA interference, and dominant-negative mutants. PEAV entry into Vero cells depended on three endocytic pathways: caveolae, clathrin, and macropinocytosis. Endocytosis requires dynamin, cholesterol, and a low pH. Rab5, Rab7, and Rab9 GTPases (but not Rab11) regulate PEAV endocytosis. PEAV particles colocalize with EEA1, Rab5, Rab7, Rab9, and Lamp-1, suggesting that PEAV translocates into early endosomes after internalization, and Rab5, Rab7, and Rab9 regulate trafficking to lysosomes before viral genome release. PEAV enters porcine intestinal cells (IPI-2I) through the same endocytic pathway, suggesting that PEAV may enter various cells through multiple endocytic pathways. This study provides new insights into the PEAV life cycle. IMPORTANCE Emerging and reemerging coronaviruses cause severe human and animal epidemics worldwide. PEAV is the first bat-like coronavirus to cause infection in domestic animals. However, the PEAV entry mechanism into host cells remains unknown. This study demonstrates that PEAV enters into Vero or IPI-2I cells through caveola/clathrin-mediated endocytosis and macropinocytosis, which does not require a specific receptor. Subsequently, Rab5, Rab7, and Rab9 regulate PEAV trafficking from early endosomes to lysosomes, which is pH dependent. The results advance our understanding of the disease and help to develop potential new drug targets against PEAV.

cFLIPL Alleviates Myocardial Ischemia-Reperfusion Injury by Inhibiting Endoplasmic Reticulum Stress.

PURPOSE: Endoplasmic reticulum stress (ERS) plays a crucial role in myocardial ischemia-reperfusion injury (MIRI). Cellular FLICE-inhibitory protein (cFLIP) is an essential regulator of apoptosis and plays a major role in regulating ERS. The present study aimed to investigate the effects of long isoform cFLIP (cFLIPL) on endogenous apoptosis and the mechanism of ERS in MIRI. METHODS: The cFLIPL recombinant adenovirus vector was used to infect H9c2 cells and Sprague-Dawley (SD) rats. After infection for 72 h, ischemia was induced for 30 min, and reperfusion was then performed for 2 h to establish the MIRI model in SD rats. H9c2 cells were hypoxic for 4 h and then reoxygenated for 12 h to simulate ischemia/reperfusion (I/R) injury. Model parameters were evaluated by assessing cardiomyocyte viability, cell death (apoptosis), and ERS-related protein expression. In addition, tunicamycin (TM), an ERS agonist, was also added to the medium for pretreatment. Coimmunoprecipitation (Co-IP) of cFLIPL and p38 MAPK protein was performed. RESULTS: cFLIPL expression was decreased in I/R injury and hypoxia/reoxygenation (H/R) injury, and cFLIPL overexpression reduced myocardial infarction in vivo and increased the viability of H9c2 cells in vitro. I/R and H/R upregulated the protein expression of GRP78, IRE-1, and PERK to induce ERS and apoptosis. Interestingly, overexpression of cFLIPL significantly inhibited ERS and subsequent apoptosis, which was reversed by an agonist of ERS. Moreover, Co-IP showed that cFLIPL attenuated ERS and was associated with inhibiting the activation of p38 protein. CONCLUSION: The expression of cFLIPL is significantly downregulated in MIRI, and it is accompanied by excessive ERS and apoptosis. Upregulated cFLIPL suppresses ERS to reduce myocardial apoptosis, which is associated with inhibiting the activity of p38 MAPK. Therefore, cFLIPL may be a potential intervention target for MIRI.