Knockdown of SlYTHDF2 Accelerates Dark-Induced Tomato Leaf Senescence by Affecting the ABA Pathway.

N6-methyladenosine (m6A) is a widespread post-transcriptional modification in eukaryotic mRNAs. Proteins with the YTH structural domain act as m6A-binding proteins by recognizing the m6A modification and regulating mRNA through this recognition. In this study, SlYTHDF2, a prototypical m6A -binding protein gene in the YTH family was expressed in various tissues, and subcellular localization analyses indicated that the SlYTHDF2 protein was localized in the nucleus and cytoplasm. SlYTHDF2 knockout lines were obtained using CRISPR/Cas9 technology and showed the senesced leaves prematurely increased endogenous ABA accumulation compared with the wild type. Moreover, we found that dark promoted leaf senescence in SlYTHDF2 knockout lines and exogenous ABA further accelerated leaf senescence under dark conditions. The qRT-PCR analysis revealed significant alterations in the expression of genes associated with the ABA pathway. Relative to the wild type, the CR-slythdf2 plants exhibited reduced levels of photosynthetic pigments, higher accumulation of reactive oxygen species, and increased damage to cell membranes. Additionally, we discovered that SlYTHDF2 interacts with the chloroplast-binding protein SlRBCS3 through yeast two-hybrid and BiFC experiments. Overall, our data suggest the important role of SlYTHDF2 in regulating tomato leaf senescence.

The potential of diallyl trisulfide for cancer prevention and treatment, with mechanism insights.

Cancer has become an important public health problem worldwide, and there is currently a lack of effective treatment and prevention strategies. Natural plant active ingredients have been proven to be a safe and highly promising method for preventing and treating cancer. It has been found that diallyl trisulfide have anticancer effects in multiple types of cancer via inhibiting cancer proliferation, enhancing chemotherapy sensitivity, inducing apoptosis/autophagy, suppressing invasion/migration, regulating microenvironment. With the deepening of research on new strategies for cancer prevention and treatment, the role of diallyl trisulfides in cancers occurrence, prognosis, and drug resistance is also receiving increasing attention. In order to better understand the relationship between diallyl trisulfides and various cancer, as well as the role and mechanism of diallyl trisulfides in cancer prevention and treatment, we briefly summarized the role and function of diallyl trisulfide in cancers.

Identification and Characterization of Extrachromosomal Circular DNA in Slimming Grass Carp.

Slimming grass carp is a commercial variety with good body form and meat quality, which is cultured by starving common grass carp in a clean flowing water environment. Compared to common grass carp, slimming grass carp has a far higher economic value. Until now, no molecular study has concentrated on the regulation mechanism of the muscle characteristics of slimming grass carp. This study first reported the gene expression profile of the muscle characteristics of slimming grass carp based on the level of extrachromosomal circular DNAs (eccDNAs). EccDNAs are double-stranded circular DNAs derived from genomic DNAs and play crucial roles in the functional regulation of a wide range of biological processes, none of which have been shown to occur in fish. Here, muscle eccDNAs from slimming grass carp and common grass carp were both generally sequenced, and the information, as well as the expression profile of eccDNAs, were compared and analysed. The findings reveal that 82,238 and 25,857 eccDNAs were detected from slimming grass carp and common grass carp, respectively. The length distribution of eccDNAs was in the range of 1~1000 bp, with two peaks at about 200 bp and 400 bp. When the expression profiles of eccDNAs between slimming grass carp and common grass carp were compared, 3523 up-regulated and 175 down-regulated eccDNAs were found. Enrichment analysis showed that these eccDNA genes were correlated with cellular structure and response, cell immunology, enzyme activity, etc. Certain differentially expressed eccDNAs involved in muscle characteristics were detected, which include myosin heavy chain, myosin light chain, muscle segment homeobox C, calsequestrin, calmodulin, etc., among which the majority of genes were linked to muscle structure and contraction. This indicates that during the process of cultivating from common grass carp to slimming grass carp, the treatment primarily affected muscle structure and contraction, making the meat quality of slimming grass carp different from that of common grass carp. This result provides molecular evidence and new insights by which to elucidate the regulating mechanism of muscle phenotypic characterisation in slimming grass carp and other fish.

Overexpression of SlALC Increases Drought and Salt Tolerance and Affects Fruit Dehiscence in Tomatoes.

The bHLH transcription factors are important plant regulators against abiotic stress and involved in plant growth and development. In this study, SlALC, a gene coding for a prototypical DNA-binding protein in the bHLH family, was isolated, and SlALC-overexpression tomato (SlALC-OE) plants were generated by Agrobacterium-mediated genetic transformation. SlALC transgenic lines manifested higher osmotic stress tolerance than the wild-type plants, estimated by higher relative water content and lower water loss rate, higher chlorophyll, reducing sugar, starch, proline, soluble protein contents, antioxidant enzyme activities, and lower MDA and reactive oxygen species contents in the leaves. In SlALC-OE lines, there were more significant alterations in the expression of genes associated with stress. Furthermore, SlALC-OE fruits were more vulnerable to dehiscence, with higher water content, reduced lignin content, SOD/POD/PAL enzyme activity, and lower phenolic compound concentrations, all of which corresponded to decreased expression of lignin biosynthetic genes. Moreover, the dual luciferase reporter test revealed that SlTAGL1 inhibits SlALC expression. This study revealed that SlALC may play a role in controlling plant tolerance to drought and salt stress, as well as fruit lignification, which influences fruit dehiscence. The findings of this study have established a foundation for tomato tolerance breeding and fruit quality improvement.

The knockout of SlMTC impacts tomato seed size and reduces resistance to salt stress in tomato.

Members of the MT-A70 family are key catalytic proteins involved in m6A methylation modifications in plants. They play diverse roles at the posttranscriptional level by regulating RNA secondary structure, selective splicing, stability, and translational efficiency, which collectively affect plant growth, development, and stress responses. In this study, we explored the function of the gene SlMTC, a Class C member of the MT-A70 family, in tomatoes by using CRISPR/Cas9 technology. Compared with the wild-type (WT), the CR-slmtc mutants exhibited decreased seed size and slower growth rates during the seedling stage, along with weaker salt tolerance and significant downregulation of stress-related genes, such as PR1, PR5, and P5CS. The qRT-PCR results revealed that the expression levels of genes involved in auxin biosynthesis (FZY1, FZY3, and FZY4) and polar transport (PIN1, PIN4, and PIN8) were lower in CR-slmtc plants than in the WT plants. In addition, yeast two-hybrid assays showed that SlMTC could interact with SlMTA, a Class A member of the MT-A70 family, providing insights into the potential mode of action of SlMTC in tomatoes. Overall, our findings indicate the critical role of SlMTC in plant growth and development as well as in response to salt stress.

Novel role of circRNAs in the drug resistance of gastric cancer: regulatory mechanisms and future for cancer therapy.

Cancer, including gastric cancer, has become a serious disease that jeopardizes public life. Currently, the main treatment methods are surgery, radiation therapy, and chemotherapy. One of the primary causes of death for patients with gastric cancer is drug resistance. Several mechanisms of anticancer drugs resistance have been reported, including changes in drugs transport and metabolism, mutations in drug targets, changes in DNA repair systems, inhibition of cell apoptosis and autophagy, gastric cancer stem cells, invasion and migration. It is becoming more widely known that non-coding RNAs, like circRNAs, play a critical role in the resistance of drugs used to treat gastric cancer. CircRNAs have a unique structure and function that is related to gastric cancer resistance, cell proliferation, apoptosis, autophagy, DNA repair systems, migration, and invasion. A clear understanding of the molecular mechanism of circRNAs mediated the resistance of gastric cancer drugs will open a new window for the treatment and management of gastric cancer. Therefore, in this review, we will summarize the current mechanism of drug resistance, and finally discuss the molecular mechanism of circRNAs in regulating the development of drug resistance in gastric cancer.

Chitosan-puerarin composite hydrogel with magnetic enhanced photothermal properties as sustained antimicrobial coatings for beef preservation.

The bactericidal properties of traditional food coatings mostly depend on the amount of fungicides present, which reduces the sustainability of food packaging. Herein, we proposed a magnetic field to precisely modulate the near-infrared (NIR) absorption activity to enhance antimicrobial coatings sustainability. Inspired by the typical grinding procedure, the assembly of CP/Fe3O4@TA nanofiber hydrogel was proposed as the coating, applying mechanical force and encouraging the collision of effective molecules of puerarin (PUE), chitosan (CS), and Fe3O4@TA NFs. This hydrogel design offers precise control over the physical and chemical properties, including appearance, viscoelasticity, and rheology. Particularly, significant changes in photothermal performance were observed as a result of magnetic regulation of NIR absorption activity. As a result, the CP/Fe3O4@TA coatings achieve effective bacteria killing performance under NIR irradiation, magnetocaloric effect, boric acid adsorption, and aggregation interference. Finally, the hydrogel coating was applied to the beef surface and serves as an effective barrier against the growth of pathogenic bacteria, thereby preserving the freshness and tenderness of the beef. The finding from this work is expected to open up a new way in active nano hydrogel coating for food preservation.

Discovery of Benzothiazol-2-ylthiophenylpyrazole-4-carboxamides as Novel Succinate Dehydrogenase Inhibitors.

Succinate dehydrogenase (SDH) has been considered an ideal target for discovering fungicides. To develop novel SDH inhibitors, in this work, 31 novel benzothiazol-2-ylthiophenylpyrazole-4-carboxamides were designed and synthesized using active fragment exchange and a link approach as promising SDH inhibitors. The findings from the tests on antifungal activity indicated that most of the synthesized compounds displayed remarkable inhibition against the fungi tested. Compound Ig N-(2-(((5-chlorobenzo[d]thiazol-2-yl)thio)methyl)phenyl)-3-(difluoromethyl)-1-methyl-1H-yrazole-4-carboxamide, with EC50 values against four kinds of fungi tested below 10 µg/mL and against Cercospora arachidicola even below 2 µg/mL, showed superior antifungal activity than that of commercial fungicide thifluzamide, and specifically compounds Ig and Im were found to show preventative potency of 90.6% and 81.3% against Rhizoctonia solani Kühn, respectively, similar to the positive fungicide thifluzamide. The molecular simulation studies suggested that hydrophobic interactions were the main driving forces between ligands and SDH. Encouragingly, we found that compound Ig can effectively promote the wheat seedlings and the growth of Arabidopsis thaliana. Our further studies indicated that compound Ig could stimulate nitrate reductase activity in planta and increase the biomass of plants.

Disparities in outcomes of colorectal cancer surgery among adults with intellectual and developmental disabilities.

BACKGROUND: Disparities in colorectal cancer screening have been documented among people with intellectual and developmental disabilities (IDD). However, surgical outcomes in this population have yet to be studied. The present work aimed to evaluate the association of IDD with outcomes following colorectal cancer resection. METHODS: All adults undergoing resection for colorectal cancer in the 2011-2020 National Inpatient Sample were identified. Multivariable linear and logistic regression models were developed to examine the association of IDD with risk factors as well as outcomes including mortality, complications, costs, length of stay (LOS), and non-home discharge. The study is limited by its retrospective nature and did not capture disease staging or time of diagnosis. RESULTS: Among 722,736 patients undergoing colorectal cancer resection, 2,846 (0.39%) had IDD. Compared to patients without IDD, IDD patients were younger and had a higher burden of comorbidities. IDD status was associated with increased odds of non-elective admission (AOR 1.40 [95% CI 1.14-1.73]) and decreased odds of treatment at high-volume centers (AOR 0.64 [95% CI 0.51-0.81]). Furthermore, IDD patients experienced significantly greater LOS (9 vs 6 days, p<0.001) and hospitalization costs ($23,500 vs $19,800, p<0.001) relative to neurotypical patients. Upon risk adjustment, IDD was significantly associated with 2-fold increased odds of mortality (AOR 2.34 [95% CI 1.48-3.71]), 1.4-fold increase in complications (AOR 1.41 [95% CI 1.15-1.74]), and 6.8-fold increase in non-home discharge (AOR 6.83 [95% CI 5.46-8.56]). CONCLUSIONS: IDD patients undergoing colorectal cancer resection experience increased likelihood of non-elective admission, adverse clinical outcomes, and resource use. Our findings highlight the need for more accessible screening and patient-centered interventions to improve quality of surgical care for this at-risk population.

Center-level variation in hospitalization costs of pancreaticoduodenectomy for pancreatic cancer.

BACKGROUND: Pancreaticoduodenectomy is a highly morbid operation with significant resource utilization. Using a national cohort, we examined the interhospital variation in pancreaticoduodenectomy hospitalization cost in the United States. METHODS: Adults undergoing elective pancreaticoduodenectomy in the setting of pancreatic cancer were tabulated from the 2016-2020 Nationwide Readmissions Database. A 2-level mixed-effects model was developed to evaluate the interhospital variation in pancreaticoduodenectomy hospitalization costs. Institutions within the top decile of risk-adjusted expenditures were defined as high-cost hospitals. Multivariable regression models were fitted to examine the association between high-cost hospital status and outcomes of interest. To account for the effects of complications on expenditures, a subgroup analysis comprising of patients with no adverse events was conducted. RESULTS: The study included an estimated 24,779 patients with a median hospitalization cost of $38,800. After mixed-effects modeling, 40.9% of the cost variation was attributable to hospital, rather than patient, factors. Multivariable regression models revealed an association between high-cost hospital status and greater odds of complications and longer length of stay. Among patients without an adverse event, interhospital cost variation remained significant at 61.0%, and treatment at high-cost hospitals was similarly linked to longer length of stay. CONCLUSION: Our study identified significant interhospital variation in pancreaticoduodenectomy hospitalization costs in the United States. Although high-cost hospital status was associated with increased odds of complications, variation remained significant even among patients without an adverse event. These results suggest the important role of hospital practices as contributors to expenditures. Further efforts to identify drivers of costs and standardize pancreatic surgical care are warranted.

Dynamic Covalent Hydrogel as a Single-Dose Vaccine Adjuvant for Sustained Antigen Release and Significantly Elevated Humoral Immunity.

Vaccine is the most important way for fighting against infection diseases. However, multiple injections and unsatisfied immune responses are the main obstacles for current vaccine application. Herein, a dynamic covalent hydrogel (DCH) is used as a single-dose vaccine adjuvant for eliciting robust and sustained humoral immunity. By adjusting the mass ratio of the DCH gel, 10-30 d constant release of the loaded recombinant protein antigens is successfully realized, and it is proved that sustained release of antigens can significantly improve the vaccine efficacy. When loading SARS-CoV-2 RBD (Wuhan and Omicron BA.1 strains) antigens into this DCH gel, an over 32 000 times and 8000 times improvement is observed in antigen-specific antibody titers compared to conventional Aluminum adjuvanted vaccines. The universality of this DCH gel adjuvant is confirmed in a Nipah G antigen test as well as a H1N1 influenza virus antigen test, with much improved protection of C57BL/6 mice against H1N1 virus infection than conventional Aluminum adjuvanted vaccines. This sustainably released, single-dose DCH gel adjuvant provides a new promising option for designing next-generation infection vaccines.

Identification of the cytochrome P450 gene AccCYP6A13 in Apis cerana cerana and its response to environmental stress.

Cytochrome P450 plays a crucial role in regulating insect growth, development, and resisting a variety of stresses. Insect metamorphosis and response to external stress are altered by deleting CYP450 genes. In this study, we identified and analyzed a novel gene of CYP450 family, AccCYP6A13, from Apis cerana cerana, and explored its role in the response of Apis cerana cerana to adverse external stressors. It was found that the expression of AccCYP6A13 was spatiotemporal specificity. The expression level increased with age and reached its highest value in the adult stage. The primarily expressiong location were legs, brain, and epidermis of honeybees. Stress conditions can affect the expression of AccCYP6A13 depending on treatment times. RNA interference experiments have shown that knocking down AccCYP6A13 reduces antioxidant activity and deactivates detoxification enzymes, resulting in oxidative damage accumulation and a decline in detoxification capability in bees, as well as inhibiting numerous antioxidant genes. Additionally, knockdown of the AccCYP6A13 gene in Apis cerana cerana resulted in increased sensitivity to pesticides and increased mortality when treated with neonicotinoid pesticides such as thiamethoxam. AccCYP6A13 overexpression in a prokaryotic system further confirmed its role in resistance to oxidative stress. To summarize, AccCYP6A13 may play an essential role in the normal development and response to environmental stress in Apis cerana cerana. Furthermore, this study contributed to the theoretical understanding of bee resistance biology.

A novel host restriction factor MRPS6 mediates the inhibition of PDCoV infection in HIEC-6 cells.

Introduction: Porcine deltacoronavirus (PDCoV) is a zoonotic pathogen with a global distribution, capable of infecting both pigs and humans. To mitigate the risk of cross-species transmission and potential outbreaks, it is crucial to characterize novel antiviral genes, particularly those from human hosts. Methods: This research used HIEC-6 to investigate PDCoV infection. HIEC-6 cells were infected with PDCoV. Samples were collected 48 h postinfection for proteomic analysis. Results: We discovered differential expression of MRPS6 gene at 48 h postinfection with PDCoV in HIEC-6 cells. The gene expression initially increased but then decreased. To further explore the role of MRPS6 in PDCoV infection, we conducted experiments involving the overexpression and knockdown of this gene in HIEC-6 and Caco2 cells, respectively. Our findings revealed that overexpression of MRPS6 significantly inhibited PDCoV infection in HIEC-6 cells, while knockdown of MRPS6 in Caco2 cells led to a significant increase of virus titer. Furthermore, we investigated the correlation between PDCoV infection and the expression of MRPS6. Subsequent investigations demonstrated that MRPS6 exerted an augmentative effect on the production of IFN-ß through interferon pathway activation, consequently impeding the progression of PDCoV infection in cellular systems. In conclusion, this study utilized proteomic analysis to investigate the differential protein expression in PDCoV-infected HIEC-6 cells, providing evidence for the first time that the MRPS6 gene plays a restrictive role in PDCoV virus infection. Discussion: Our findings initially provide the validation of MRPS6 as an upstream component of IFN-ß pathway, in the promotion of IRF3, IRF7, STAT1, STAT2 and IFN-ß production of HIEC-6 via dual-activation from interferon pathway.

Complex Droplet Microreactor for Highly Efficient and Controllable Esterification and Cascade Reactions.

A highly efficient complex emulsion microreactor has been successfully developed for multiphasic water-labile reactions, providing a powerful platform for atom economy and spatiotemporal control of reaction kinetics. Complex emulsions, composing a hydrocarbon phase (H) and a fluorocarbon phase (F) dispersed in an aqueous phase (W), are fabricated in batch scale with precisely controlled droplet morphologies. A biphasic esterification reaction between 2-bromo-1,2-diphenylethane-1-ol (BPO) and perfluoro-heptanoic acid (PFHA) is chosen as a reversible and water-labile reaction model. The conversion reaches up to 100 % under mild temperature without agitation, even with nearly equivalent amounts of reactants. This efficiency surpasses all reported single emulsion microreactors, i. e., 84~95 %, stabilized by various emulsifiers with different catalysts, which typically necessitate continuous stirring, a high excess of one reactant, and/or extended reaction time. Furthermore, over 3 times regulation threshold in conversion rate is attained by manipulating the droplet morphologies, including size and topology, e. g., transition from completely engulfed F/H/W double to partially engulfed (F+H)/W Janus. Addition-esterification, serving as a model for triple phasic cascade reaction, is also successfully implemented under agitating-free and mild temperature with controlled reaction kinetics, demonstrating the versatility and effectiveness of the complex emulsion microreactor.

Current Status of Contralateral Prophylactic Mastectomy: Investigating Structural Racial Disparity.

BACKGROUND: Contralateral prophylactic mastectomy (CPM) remains a personal decision, influenced by psychosocial factors, including cosmesis and peace of mind. Although use of CPM is disproportionately low among Black patients, the degree to which these disparities are driven by patient- vs hospital-level factors remains unknown. STUDY DESIGN: Patients undergoing mastectomy for nonmetastatic ductal or lobular breast cancer were tabulated using the National Cancer Database from 2004 to 2020. The primary endpoint was receipt of CPM. Multivariable logistic regression models were constructed with interaction terms between Black-serving hospital (BSH) status and patient race to evaluate associations with CPM. Cox proportional hazard models were used to evaluate long-term survival. RESULTS: Of 597,845 women studied, 70,911 (11.9%) were Black. After multivariable adjustment, Black race (adjusted odds ratio 0.65, 95% CI 0.64 to 0.67) and treatment at BSH (adjusted odds ratio 0.84, 95% CI 0.83 to 0.85) were independently linked to lower odds of CPM. Although predicted probability of CPM was universally lower at higher BSH, Black patients faced a steeper reduction compared with White patients. Receipt of CPM was linked to improved survival (hazard ratio [HR] 0.84, 95% CI 0.83 to 0.86), whereas Black race was associated with a greater HR of 10-year mortality (HR 1.14, 95% CI 1.12 to 1.17). CONCLUSIONS: Hospitals serving a greater proportion of Black patients are less likely to use CPM, suggestive of disparities in access to CPM at the institutional level. Further research and education are needed to characterize surgeon-specific and institutional practices in patient counseling and shared decision-making that shape disparities in access to CPM.

Interhospital Transfer for Emergency General Surgery: A Contemporary National Analysis.

BACKGROUND: Patients undergoing emergency general surgery (EGS) often require complex management and transfer to higher acuity facilities, especially given increasing national efforts aimed at centralizing care. We sought to characterize factors and evaluate outcomes associated with interhospital transfer using a contemporary national cohort. METHODS: All adult hospitalizations for EGS (appendectomy, cholecystectomy, laparotomy, lysis of adhesions, small/large bowel resection, and perforated ulcer repair) ≤2 days of admission were identified in the 2016-2020 National Inpatient Sample. Patients initially admitted to a different institution and transferred to the operating hospital comprised the Transfer cohort (others: Non-Transfer). Multivariable models were developed to consider the association of Transfer with outcomes of interest. RESULTS: Of ∼1 653 169 patients, 107 945 (6.5%) were considered the Transfer cohort. The proportion of patients experiencing interhospital transfer increased from 5.2% to 7.7% (2016-2020, P < .001). On average, Transfer was older, more commonly of White race, and of a higher Elixhauser comorbidity index. After adjustment, increasing age, living in a rural area, receiving care in the Midwest, and decreasing income quartile were associated with greater odds of interhospital transfer. Following risk adjustment, Transfer remained linked with increased odds of in-hospital mortality (AOR 1.64, CI 1.49-1.80), as well as any perioperative complication (AOR 1.33, CI 1.27-1.38; Reference: Non-Transfer). Additionally, Transfer was associated with significantly longer duration of hospitalization (ß + 1.04 days, CI + .91-1.17) and greater costs (ß+$3,490, CI + 2840-4140). DISCUSSION: While incidence of interhospital transfer for EGS is increasing, transfer patients face greater morbidity and resource utilization. Novel interventions are needed to optimize patient selection and improve post-transfer outcomes.

Income-Based Disparities in Outcomes Following Pediatric Appendectomy: A National Analysis.

BACKGROUND: Appendectomy remains a common pediatric surgical procedure with an estimated 80,000 operations performed each year. While prior work has reported the existence of racial disparities in postoperative outcomes, we sought to characterize potential income-based inequalities using a national cohort. METHODS: All non-elective pediatric (<18 years) hospitalizations for appendectomy were tabulated in the 2016-2020 National Inpatient Sample. Only those in the highest (HI) and lowest income (LI) quartiles were considered for analysis. Multivariable regression models were developed to assess the independent association of income and postoperative major adverse events (MAE). RESULTS: Of an estimated 87,830 patients, 36,845 (42.0%) were HI and 50,985 (58.0%) were LI. On average, LI patients were younger (11 [7-14] vs 12 [8-15] years, P < .001), more frequently insured by Medicaid (70.7 vs 27.3%, P < .05), and more commonly of Hispanic ethnicity (50.8 vs 23.4%, P < .001). Following risk adjustment, the LI cohort was associated with greater odds of MAE (adjusted odds ratio [AOR] 1.30 95% confidence interval [CI] 1.06-1.64). Specifically, low-income status was linked with increased odds of infectious (AOR 1.65, 95% CI 1.12-2.42) and respiratory (AOR 1.67, 95% CI 1.06-2.62) complications. Further, LI was associated with a $1670 decrement in costs ([2220-$1120]) and a +.32-day increase in duration of stay (95% CI [.21-.44]). CONCLUSION: Pediatric patients of the lowest income quartile faced increased risk of major adverse events following appendectomy compared to those of highest income. Novel risk stratification methods and standardized care pathways are needed to ameliorate socioeconomic disparities in postoperative outcomes.

Association of substance-use disorder with outcomes of major elective abdominal operations: A contemporary national analysis.

Background: Affecting >20million people in the U.S., including 4 % of all hospitalized patients, substance use disorder (SUD) represents a growing public health crisis. Evaluating a national cohort, we aimed to characterize the association of concurrent SUD with perioperative outcomes and resource utilization following elective abdominal operations. Methods: All adult hospitalizations entailing elective colectomy, gastrectomy, esophagectomy, hepatectomy, and pancreatectomy were tabulated from the 2016-2020 National Inpatient Sample. Patients with concurrent substance use disorder, comprising alcohol, opioid, marijuana, sedative, cocaine, inhalant, hallucinogen, or other psychoactive/stimulant use, were considered the SUD cohort (others: nSUD). Multivariable regression models were constructed to evaluate the independent association between SUD and key outcomes. Results: Of ∼1,088,145 patients, 32,865 (3.0 %) comprised the SUD cohort. On average, SUD patients were younger, more commonly male, of lowest quartile income, and of Black race. SUD patients less frequently underwent colectomy, but more often pancreatectomy, relative to nSUD.Following risk adjustment and with nSUD as reference, SUD demonstrated similar likelihood of in-hospital mortality, but remained associated with increased odds of any perioperative complication (Adjusted Odds Ratio [AOR] 1.17, CI 1.09-1.25). Further, SUD was linked with incremental increases in adjusted length of stay (ß + 0.90 days, CI +0.68-1.12) and costs (ß + $3630, CI +2650-4610), as well as greater likelihood of non-home discharge (AOR 1.54, CI 1.40-1.70). Conclusions: Concurrent substance use disorder was associated with increased complications, resource utilization, and non-home discharge following major elective abdominal operations. Novel interventions are warranted to address increased risk among this vulnerable population and address significant disparities in postoperative outcomes.

Transcriptomic Analysis of PDCoV-Infected HIEC-6 Cells and Enrichment Pathways PI3K-Akt and P38 MAPK.

Porcine Deltacoronavirus (PDCoV) is a newly identified coronavirus that causes severe intestinal lesions in piglets. However, the understanding of how PDCoV interacts with human hosts is limited. In this study, we aimed to investigate the interactions between PDCoV and human intestinal cells (HIEC-6) by analyzing the transcriptome at different time points post-infection (12 h, 24 h, 48 h). Differential gene analysis revealed a total of 3560, 5193, and 4147 differentially expressed genes (DEGs) at 12 h, 24 h, and 48 h, respectively. The common genes among the DEGs at all three time points were enriched in biological processes related to cytokine production, extracellular matrix, and cytokine activity. KEGG pathway analysis showed enrichment of genes involved in the p53 signaling pathway, PI3K-Akt signaling pathway, and TNF signaling pathway. Further analysis of highly expressed genes among the DEGs identified significant changes in the expression levels of BUB1, DDIT4, ATF3, GBP2, and IRF1. Comparison of transcriptome data at 24 h with other time points revealed 298 DEGs out of a total of 6276 genes. KEGG analysis of these DEGs showed significant enrichment of pathways related to viral infection, specifically the PI3K-Akt and P38 MAPK pathways. Furthermore, the genes EFNA1 and KITLG, which are associated with viral infection, were found in both enriched pathways, suggesting their potential as therapeutic or preventive targets for PDCoV infection. The enhancement of PDCoV infection in HIEC-6 was observed upon inhibition of the PI3K-Akt and P38 MAPK signaling pathways using sophoridine. Overall, these findings contribute to our understanding of the molecular mechanisms underlying PDCoV infection in HIEC-6 cells and provide insights for developing preventive and therapeutic strategies against PDCoV infection.