Limited debridement combined with ReCell® Techniques for deep second-degree burns.

BACKGROUND: The purpose of this article is to introduce a method that combines limited debridement and ReCell® autologous cell regeneration techniques for the treatment of deep second-degree burn wounds. METHOD: A total of 20 patients suffered with deep second-degree burns less than 10% of total body surface area (TBSA) who were admitted to our department, from June 2019 to June 2021, participated in this study. These patients first underwent limited debridement with an electric/pneumatic dermatome, followed by the ReCell® technique for secondary wounds. Routine treatment was applied to prevent scarring after the wound healed. Clinical outcomes were scored using the Vancouver Scar Scale (VSS). RESULTS: All wounds of the patients healed completely. One patient developed an infection in the skin graft area and finally recovered by routine dressing changes. The average healing time was 12 days (range: 10-15 days). The new skin in the treated area was soft and matched the colour of the surrounding normal skin and the VSS score ranged from 3~5 for each patient. Of the 20 patients, 19 were very satisfied and 1 was satisfied. CONCLUSIONS: This article reports a useful treatment method that combines electric dermatome-dependent limited debridement and the ReCell® technique for the treatment of deep second-degree burn wounds. It is a feasible and effective strategy that is easy to implement and minimally invasive, and it is associated with a short healing time, mild scar formation and little damage to the donor skin area.

Inhibition of Drp1-mediated mitochondrial fission improves contrast-induced acute kidney injury by targeting the mROS-TXNIP-NLRP3 inflammasome axis.

Acute kidney injury (AKI) is a critical complication known for their extremely high mortality rate and lack of effective clinical therapy. Disorders in mitochondrial dynamics possess a pivotal role in the occurrence and progression of contrast-induced nephropathy (CIN) by activating NLRP3 inflammasome. The activation of dynamin-related protein-1 (Drp1) can trigger mitochondrial dynamic disorders by regulating excessive mitochondrial fission. However, the precise role of Drp1 during CIN has not been clarified. In vivo experiments revealed that inhibiting Drp1 through Mdivi-1 (one selective inhibitor of Drp1) can significantly decrease the expression of p-Drp1 (Ser616), mitochondrial p-Drp1 (Ser616), mitochondrial Bax, mitochondrial reactive oxygen species (mROS), NLRP3, caspase-1, ASC, TNF-α, IL-1ß, interleukin (IL)-18, IL-6, creatinine (Cr), malondialdehyde (MDA), blood urea nitrogen (BUN), and KIM-1. Moreover, Mdivi-1 reduced kidney pathological injury and downregulated the interaction between NLRP3 and thioredoxin-interacting protein (TXNIP), which was accompanied by decreased interactions between TRX and TXNIP. This resulted in increasing superoxide dismutase (SOD) and CAT activity, TRX expression, up-regulating mitochondrial membrane potential, and augmenting ATP contents and p-Drp1 (Ser616) levels in the cytoplasm. However, it did not bring impact on the expression of p-Drp1 (Ser637) and TXNIP. Activating Drp-1though Acetaldehyde abrogated the effects of Mdivi-1. In addition, the results of in vitro studies employing siRNA-Drp1 and plasmid-Drp1 intervention in HK-2 cells treated with iohexol were consistent with the in vivo experiments. Our findings revealed inhibiting Drp1 phosphorylation at Ser616 could ameliorate iohexol -induced acute kidney injury though alleviating the activation of the TXNIP-NLRP3 inflammasome pathway.

Cerastecins inhibit membrane lipooligosaccharide transport in drug-resistant Acinetobacter baumannii.

Carbapenem-resistant Acinetobacter baumannii infections have limited treatment options. Synthesis, transport and placement of lipopolysaccharide or lipooligosaccharide (LOS) in the outer membrane of Gram-negative bacteria are important for bacterial virulence and survival. Here we describe the cerastecins, inhibitors of the A. baumannii transporter MsbA, an LOS flippase. These molecules are potent and bactericidal against A. baumannii, including clinical carbapenem-resistant Acinetobacter baumannii isolates. Using cryo-electron microscopy and biochemical analysis, we show that the cerastecins adopt a serpentine configuration in the central vault of the MsbA dimer, stalling the enzyme and uncoupling ATP hydrolysis from substrate flipping. A derivative with optimized potency and pharmacokinetic properties showed efficacy in murine models of bloodstream or pulmonary A. baumannii infection. While resistance development is inevitable, targeting a clinically unexploited mechanism avoids existing antibiotic resistance mechanisms. Although clinical validation of LOS transport remains undetermined, the cerastecins may open a path to narrow-spectrum treatment modalities for important nosocomial infections.

A meta-analysis highlights the cross-resistance of plants to drought and salt stresses from physiological, biochemical, and growth levels.

In nature, drought and salt stresses often occur simultaneously and affect plant growth at multiple levels. However, the mechanisms underlying plant responses to drought and salt stresses and their interactions are still not fully understood. We performed a meta-analysis to compare the effects of drought, salt, and combined stresses on plant physiological, biochemical, morphological and growth traits, analyze the different responses of C3 and C4 plants, as well as halophytes and non-halophytes, and identify the interactive effects on plants. There were numerous similarities in plant responses to drought, salt, and combined stresses. C4 plants had a more effective antioxidant defense system, and could better maintain above-ground growth. Halophytes could better maintain photosynthetic rate (Pn) and relative water content (RWC), and reduce growth as an adaptation strategy. The responses of most traits (Pn, RWC, chlorophyll content, soluble sugar content, H2O2 content, plant dry weight, etc.) to combined stress were less-than-additive, indicating cross-resistance rather than cross-sensitivity of plants to drought and salt stresses. These results are important to improve our understanding of drought and salt cross-resistance mechanisms and further induce resistance or screen-resistant varieties under stress combination.

A novel digital intermediate frequency module for hyperspectral microwave radiometers based on the parallel fast Fourier transform algorithm.

Microwave radiometers, possessing all-day and all-weather operational capabilities, are extensively utilized in the exploration of planetary atmospheres and surfaces. The potential of the hyperspectral detection technology to enhance the precision and resolution of microwave radiometer detection has made it a crucial research focus. This paper introduces an intermediate frequency (IF) module for hyperspectral microwave radiometers. The IF module is constructed with two 6.4 gigabit samples per second sampling-rate analog-to-digital converter (ADC) chips and a Xilinx Virtex-7 field programmable gate array. By implementing a parallel fast Fourier transform algorithm and a pipeline architecture, the IF module can efficiently process all ADC sampling data in real-time, generating 512 channels of output for each ADC. The test results, including linearity, sensitivity, and flatness, are presented and thoroughly analyzed for the IF module. Furthermore, the module is interfaced with the radio frequency front-end of the microwave radiometer to measure hot and cold calibration sources and assess its sensitivity. When combined with a suitable front-end receiver, the IF module can form a radiometer system suitable for various applications of microwave remote sensing.

Divergent Total Syntheses of Lycorine Alkaloids via a Sequential C-H Functionalization Strategy.

A Pd-catalyzed one-pot sequential C-H functionalization strategy was utilized to prepare four lycorine alkaloids and one pseudo-lycorine alkaloid from the common intermediate 4. By switching the followed oxidative conditions of air, DMSO/H2O/I2, and DMSO/O2, based on the Pd(PPh3)4/K2CO3/toluene catalytic system, three key intermediates 12a, 12b, and 12c with different substitution patterns could be obtained in a well-controlled manner. As a result, four natural products γ-lycorane, hippadine, anhydrolycorinone, and anhydrolycorine as well as a pseudo-lycorine alkaloid Δ(4a,10b)-6-oxodihydrolycorine were successfully synthesized within 10 steps through this divergent route.

Lipidomic and transcriptomic analysis of the increase in eicosapentaenoic acid under cobalamin deficiency of Schizochytrium sp.

Schizochytrium sp. is a heterotrophic microorganism capable of accumulating polyunsaturated fatty acids and has achieved industrial production of docosahexaenoic acid (DHA). It also has the potential for eicosapentaenoic acid (EPA) production. In this study, it was found that the cell growth, lipid synthesis and fatty acid composition of Schizochytrium sp. were significantly affected by the level of cobalamin in the medium, especially with regard to the content of EPA in the fatty acids. The content of EPA in the fatty acids increased 17.91 times, reaching 12.00%, but cell growth and lipid synthesis were significantly inhibited under cobalamin deficiency. The response mechanism for this phenomenon was revealed through combined lipidomic and transcriptomic analysis. Although cell growth was inhibited under cobalamin deficiency, the genes encoding key enzymes in central carbon metabolism were still up-regulated to provide precursors (Acetyl-CoA) and reducing power (NADPH) for the synthesis and accumulation of fatty acids. Moreover, the main lipid subclasses observed during cobalamin deficiency were glycerolipids (including glycerophospholipids), with EPA primarily distributed in them. The genes involved in the biosynthesis of these lipid subclasses were significantly up-regulated, such as the key enzymes in the Kennedy pathway for the synthesis of triglycerides. Thus, this study provided insights into the specific response of Schizochytrium sp. to cobalamin deficiency and identified a subset of new genes that can be engineered for modification.

Malignancy diagnosis of liver lesion in contrast enhanced ultrasound using an end-to-end method based on deep learning.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) is considered as an efficient tool for focal liver lesion characterization, given it allows real-time scanning and provides dynamic tissue perfusion information. An accurate diagnosis of liver lesions with CEUS requires a precise interpretation of CEUS images. However,it is a highly experience dependent task which requires amount of training and practice. To help improve the constrains, this study aims to develop an end-to-end method based on deep learning to make malignancy diagnosis of liver lesions using CEUS. METHODS: A total of 420 focal liver lesions with 136 benign cases and 284 malignant cases were included. A deep learning model based on a two-dimensional convolution neural network, a long short-term memory (LSTM), and a linear classifier (with sigmoid) was developed to analyze the CEUS loops from different contrast imaging phases. For comparison, a 3D-CNN based method and a machine-learning (ML)-based time-intensity curve (TIC) method were also implemented for performance evaluation. RESULTS: Results of the 4-fold validation demonstrate that the mean AUC is 0.91, 0.88, and 0.78 for the proposed method, the 3D-CNN based method, and the ML-based TIC method, respectively. CONCLUSIONS: The proposed CNN-LSTM method is promising in making malignancy diagnosis of liver lesions in CEUS without any additional manual features selection.

Nuclear to cytoplasmic transport is a druggable dependency in MYC-driven hepatocellular carcinoma.

The MYC oncogene is often dysregulated in human cancer, including hepatocellular carcinoma (HCC). MYC is considered undruggable to date. Here, we comprehensively identify genes essential for survival of MYChigh but not MYClow cells by a CRISPR/Cas9 genome-wide screen in a MYC-conditional HCC model. Our screen uncovers novel MYC synthetic lethal (MYC-SL) interactions and identifies most MYC-SL genes described previously. In particular, the screen reveals nucleocytoplasmic transport to be a MYC-SL interaction. We show that the majority of MYC-SL nucleocytoplasmic transport genes are upregulated in MYChigh murine HCC and are associated with poor survival in HCC patients. Inhibiting Exportin-1 (XPO1) in vivo induces marked tumor regression in an autochthonous MYC-transgenic HCC model and inhibits tumor growth in HCC patient-derived xenografts. XPO1 expression is associated with poor prognosis only in HCC patients with high MYC activity. We infer that MYC may generally regulate and require altered expression of nucleocytoplasmic transport genes for tumorigenesis.

Prevalence and Factors Contributing to Fear of Recurrence in Breast Cancer Patients and Their Partners: A Cross-Sectional Study.

Objective: The fear of cancer recurrence (FCR) is a generalized psychological problem among cancer patients and their spouses. The purpose of this study is to investigate the current status of cancer recurrence fear among breast cancer patients and their spouses, as well as its predictive factors. Methods: A total of 155 breast cancer patients and their partners between March 2022 to Feb 2023 were selected from Affiliated Hospital of Jiangnan University. The survey was investigated by fear of progression questionnaire-short form (FoP­Q­SF), fear of progression questionnaire-short form for partners (FoP-Q-SF/P), family resilience questionnaire (FaRE), and health literacy management scale (HeLMS). Predictors were assessed using univariate and multivariable regression analyses. Results: 52.9% (n=82) of breast cancer patients and 51.6% (n=80) of their spouses experienced high levels of fear of cancer recurrence (FCR). There was a positive correlation between the FCR of the patients and their spouses, while family resilience and health literacy were statistically significant negative predictive factors for breast cancer patients' fear of cancer recurrence. Conclusion: In summary, the study found that the partner's FCR, health literacy and family resilience were closely related to the FCR in breast cancer patients. Therefore, healthcare workers can reduce the patient's FCR by reducing the FCR in spouses, improving patients' health literacy and family resilience in the future. In practical application, these findings hold significant implications for developing comprehensive care plans and interventions targeting FCR in breast cancer patients. By focusing on patients' partners and providing appropriate support and resources, healthcare professionals can promote patients' psychological well-being and overall health, leading to improved quality of life.

Multifunctional metal-coordinated Co-assembled carrier-free nanoplatform based on dual-drugs for ferroptosis-mediated cocktail therapy of hepatocellular carcinoma growth and metastasis.

The heterogeneity of hepatocellular carcinoma (HCC) and the complexity of the tumor microenvironment (TME) pose challenges to efficient drug delivery and the antitumor efficacy of combined or synergistic therapies. Herein, a metal-coordinated carrier-free nanodrug (named as USFe3+ LA NPs) was developed for ferroptosis-mediated multimodal synergistic anti-HCC. Natural product ursolic acid (UA) was incorporated to enhance the sensitivity of tumor cells to sorafenib (SRF). Surface decoration of cell penetration peptide and epithelial cell adhesion molecule aptamer facilitated the uptake of USFe3+ LA NPs by HepG2 cells. Meanwhile, Fe3+ ions could react with intracellular hydrogen peroxide, generating toxic hydroxyl radical (·OH) for chemodynamical therapy (CDT) and amplified ferroptosis by cystine/glutamate antiporter system (System Xc-), which promoted the consumption of glutathione (GSH) and inhibited the expression of glutathione peroxidase 4 (GPX4). Notably, these all-in-one nanodrugs could inhibit tumor metastasis and induced immunogenic cell death (ICD). Last but not least, the nanodrugs demonstrated favorable biocompatibility, augmenting the immune response against the programmed death-ligand 1 (PD-L1) by increasing cytotoxic T cell infiltration. In vivo studies revealed significant suppression of tumor growth and distant metastasis. Overall, our work introduced a novel strategy for applications of metal-coordinated co-assembled carrier-free nano-delivery system in HCC combination therapy, especially in the realms of cancer metastasis prevention and immunotherapy.

Cyclosporine-A induced cytotoxicity within HepG2 cells by inhibiting PXR mediated CYP3A4/CYP3A5/MRP2 pathway.

Cyclosporine-A (CsA) is currently used to treat immune rejection after organ transplantation as a commonly used immunosuppressant. Liver injury is one of the most common adverse effects of CsA, whose precise mechanism has not been fully elucidated. Pregnane X receptor (PXR) plays a critical role in mediating drug-induced liver injury as a key regulator of drug and xenobiotic clearance. As a nuclear receptor, PXR transcriptionally upregulates the expression of drug-metabolizing enzymes and drug transporters, including cytochrome P4503A (CPY3A) and multidrug resistance-associated protein 2 (MRP2). Our study established CsA-induced cytotoxic hepatocytes in an in vitro model, demonstrating that CsA dose-dependently increased the aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) level secreted in the HepG2 cell supernatant, as well as viability and oxidative stress of HepG2 cells. CsA also dose-dependently decreased the PXR, CYP3A4, CPY3A5, and MRP2 levels of HepG2 cells. Mechanistically, altering the expression of PXR, CYP3A4, CYP3A5, and MRP2 affected the impact of CsA on AST and LDH levels. Moreover, altering the expression of PXR also changed the level of CYP3A4, CPY3A5, and MRP2 of HepG2 cells treated by CsA. Our presented findings provide experimental evidence that CsA-induced liver injury is PXR tightly related. We suggest that PXR represents an attractive target for therapy of liver injury due to its central role in the regulation of the metabolizing enzymes CYP3A and MRP2-mediated bile acid transport and detoxification.

Fluorinated Isoindolinone-Based Glucosylceramide Synthase Inhibitors with Low Human Dose Projections.

Inhibition of glucosylceramide synthase (GCS) has been proposed as a therapeutic strategy for the treatment of Parkinson's Disease (PD), particularly in patients where glycosphingolipid accumulation and lysosomal impairment are thought to be contributing to disease progression. Herein, we report the late-stage optimization of an orally bioavailable and CNS penetrant isoindolinone class of GCS inhibitors. Starting from advanced lead 1, we describe efforts to identify an improved compound with a lower human dose projection, minimal P-glycoprotein (P-gp) efflux, and acceptable pregnane X receptor (PXR) profile through fluorine substitution. Our strategy involved the use of predicted volume ligand efficiency to advance compounds with greater potential for low human doses down our screening funnel. We also applied minimized electrostatic potentials (Vmin) calculations for hydrogen bond acceptor sites to rationalize P-gp SAR. Together, our strategies enabled the alignment of a lower human dose with reduced P-gp efflux, and favorable PXR selectivity for the discovery of compound 12.

[Relationship of triglyceride-glucose index and its derivatives with blood pressure abnormalities in adolescents: an analysis based on a restricted cubic spline model]. / åŸºäºŽé™åˆ¶æ€§ç«‹æ–¹æ ·æ¡æ¨¡åž‹åˆ†æžé’å°‘å¹´ä¸‰é °ç”˜æ²¹-è‘¡è„ç³–æŒ‡æ•°åŠå ¶è¡ç”ŸæŒ‡æ•°ä¸Žè¡€åŽ‹å¼‚å¸¸çš„å ³ç³».

OBJECTIVES: To explore the relationship of triglyceride-glucose index (TyG), triglyceride-glucose-body mass index (TyG-BMI), and triglyceride-glucose-waist circumference index (TyG-WC) with blood pressure abnormalities in adolescents, providing theoretical basis for the prevention and control of hypertension in adolescents. METHODS: A stratified cluster sampling method was used to select 1 572 adolescents aged 12 to 18 years in Yinchuan City for questionnaire surveys, physical measurements, and laboratory tests. Logistic regression analysis and restricted cubic spline analysis were employed to examine the relationship of TyG, TyG-BMI, and TyG-WC with blood pressure abnormalities in adolescents. RESULTS: Multivariable logistic regression analysis revealed that after adjusting for confounding factors, the groups with the highest quartile of TyG, TyG-BMI, and TyG-WC had 1.48 times (95%CI: 1.07-2.04), 3.71 times (95%CI: 2.67-5.15), and 4.07 times (95%CI: 2.89-5.73) higher risks of blood pressure abnormalities compared to the groups with the lowest quartile, respectively. Moreover, as the levels of TyG, TyG-BMI, and TyG-WC increased, the risk of blood pressure abnormalities gradually increased (P<0.05). A non-linear dose-response relationship was observed between TyG-BMI and the risk of blood pressure abnormalities (P overall trend<0.001, P non-linearity=0.002). Linear dose-response relationships were found between TyG and the risk of blood pressure abnormalities (P overall trend<0.001, P non-linearit =0.232), and between TyG-WC and the risk of blood pressure abnormalities (P overall trend<0.001, P non-linearity=0.224). CONCLUSIONS: Higher levels of TyG and its derivatives are associated with an increased risk of blood pressure abnormalities in adolescents, with linear or non-linear dose-response relationships.

Synergistic anti-tumor effect of dual drug co-assembled nanoparticles based on ursolic acid and sorafenib.

Both ursolic acid (UA) and sorafenib (Sora) have been generally utilized in cancer treatment, and the combination of the two has also shown a good anti-tumor effect. However, single-agent therapy for Hepatocellular carcinoma (HCC) has the disadvantages of multi-drug resistance, poor water solubility and low bioavailability, and the application of traditional nanocarrier materials is limited due to their low drug loading and low carrier-related toxicity. Therefore, we prepared US NPs with different proportions of UA and Sora by solvent exchange method for achieving synergistic HCC therapy. US NPs had suitable particle size, good dispersibility and storage stability, which synergistically inhibited the proliferation of HepG2 cells, SMMC7721 cells and H22 cells. In addition, we also proved that US NPs were able to suppress the migration of HepG2 cells and SMMC7721 cells and reduce the adhesion ability and colony formation ability of these cells. According to the results, US NPs could degrade the membrane potential of mitochondrial, participate in cell apoptosis, and synergistically induce autophagy. Collectively, the carrier-free US NPs provide new strategies for HCC treatment and new ideas for the development of novel nano-drug delivery systems containing UA and Sora.

Evaluation of Social Determinants of Health on Dysphagia Care Pathways at a Tertiary Care Facility.

OBJECTIVES: Limited research exists evaluating the impact of social determinants of health in influencing care pathways for patients with dysphagia. A better understanding of whether these determinants correlate to altered care and resource utilization is essential as it relates to patient outcomes. STUDY DESIGN: Retrospective chart review. METHODS: All adult patients seen at a tertiary midwestern hospital were screened for ICD codes of dysphagia diagnoses from 2009 to 2019. Demographic information was collected from these patients with dysphagia including sex, race, ethnicity, and insurance status. Subgroup analysis was performed to assess referral pattern rates and types of diagnostic interventions ordered (none, videofluoroscopic swallow study, esophagram, and esophagogastroduodenoscopy). RESULTS: A total of 31,858 patients with dysphagia were seen at our institution during the study period, with a majority being female (56.36%), Caucasian (79.83%), and publicly insured (63.16%), at a median age of 60.35 years. There were no significant care delivery pattern differences based on geography/zip code analyses. African American patients were significantly more likely to have imaging or interventions performed (odds ratio [OR] 1.463, p = 0.005). Patients with public insurance also had higher rates of diagnostic study utilization (OR 1.53, p = 0.01). Only 3% of all patients with dysphagia were seen by laryngologists. CONCLUSION: No significant differences were seen in dysphagia evaluation modalities based on zip code analyses surrounding this tertiary care facility. African American patients and those with public insurance had significantly higher utilization of subsequent testing and intervention for dysphagia care. Further studies are necessary to delineate causes and outcome differences for these measurable differences in dysphagia care pathways. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1139-1146, 2024.

Heterogeneity analysis of main driving factors affecting potential evapotranspiration changes across different climate regions.

Exploring the influencing factors of potential evapotranspiration (PET) is of great significance for further understanding the causes of climate change and improving agricultural irrigation efficiency. In this study, modified Mann-Kendall analysis was used to elucidate the temporal variation characteristics of meteorological factors and PET based on a dataset from 710 meteorological stations in China. Furthermore, we revealed the main factors that influence the temporal and climate heterogeneity of PET by combining sensitivity analysis with the contribution analysis method. The results showed that 1) climate factors and PET exhibited trend changes on a yearly scale, with slope variation ranges of temperature (T), relative humidity (RH), net radiation (RN), wind speed (U) and PET of 0.03-0.04 °C/a, 0.03-0.08 %/a, 0.001-0.007[MJ/(m2/day)]/a, -0.005 to -0.012(m/s)/a and -0.30-0.38 mm/a, respectively. 2) The sensitivity coefficient fluctuated greatly inter-annually, but the trend was more pronounced inter-annually. Most sensitive factor for PET was RN in hyperarid (HAR), arid (AR) and semiarid regions (SAR), while it changed to RH in semihumid (SHR) and humid regions (HR). PET was more sensitive to RN in dry and relatively wet hot seasons, while it changed to RH during wet and relatively dry cold seasons. 3) PET changes were determined by the relative changes and the sensitivity coefficient, and significant temporal heterogeneity was observed. In HAR, AR, SAR and SHR, the relative changes in T and U result in higher contributions. In HR, PET changes were primarily caused by its higher sensitivity to RH and RN. 4) In dry region and humid-cold seasons, the bigger relative changes of climate factors were the main drivers affecting PET changes, but in humid region and arid-hot seasons, the they were determined by the strong nonlinear relationship between PET and factors. This finding holds great significance for the scientific understanding of the evolution mechanism of PET under changing environments.

Response of soil respiration and carbon budget to irrigation quantity/quality and biochar addition in a mulched maize field under drip irrigation.

BACKGROUND: Biochar addition strongly alters net carbon (C) balance in agroecosystems. However, the effects of biochar addition on net C balance of maize field under various irrigation water quantities and qualities remains unclear. Thus, a field experiment combining two irrigation levels of full (W1) and deficit irrigation (W2 = 1/2 W1), two water salinity levels of fresh (S0, 0.71 g L-1 ) and brackish water (S1, 4 g L-1 ), and two biochar addition rates of 0 t ha-1 (B0) and 60 t ha-1 (B1) was conducted to investigate soil carbon dioxide (CO2 ) emissions, maize C sequestration and C budget. RESULTS: Compared with W1, W2 reduced average cumulative CO2 emissions by 6.5% and 19.9% for 2020 and 2021, respectively. The average cumulative CO2 emissions under W1S1 treatments were 5.4% and 22.3% lower than W1S0 for 2020 and 2021, respectively, whereas W2S0 and W2S1 had similar cumulative CO2 emissions in both years. Biochar addition significantly increased cumulative CO2 emissions by 17.8-23.5% for all water and salt treatments in 2020, and reduced average cumulative CO2 emissions by 11.9% for W1 but enhanced it by 8.0% for W2 in 2021. Except for W2S1, biochar addition effectively increased total maize C sequestration by 6.9-14.8% for the other three treatments through ameliorating water and salt stress over the 2 years. Compared with W1S0, W1S1 did not affect net C sequestration, but W2 treatments significantly decreased it. Biochar addition increased net C sequestration by 39.47-43.65 t C ha-1 for four water and salt treatments for the 2 years. CONCLUSION: These findings demonstrate that biochar addition is an effective strategy to increase both crop C sequestration and soil C storage under suitable water-saving irrigation methods in arid regions with limited freshwater resources. © 2023 Society of Chemical Industry.

Dual-drug controllable co-assembly nanosystem for targeted and synergistic treatment of hepatocellular carcinoma.

The effectiveness of chemotherapeutic agents for hepatocellular carcinoma (HCC) is unsatisfactory because of tumor heterogeneity, multidrug resistance, and poor target accumulation. Therefore, multimodality-treatment with accurate drug delivery has become increasingly popular. Herein, a cell penetrating peptide-aptamer dual modified-nanocomposite (USILA NPs) was successfully constructed by coating a cell penetrating peptide and aptamer onto the surface of sorafenib (Sora), ursolic acid (UA) and indocyanine green (ICG) condensed nanodrug (USI NPs) via one-pot assembly for targeted and synergistic HCC treatment. USILA NPs showed higher cellular uptake and cytotoxicity in HepG2 and H22 cells, with a high expression of epithelial cell adhesion molecule (EpCAM). Furthermore, these NPs caused more significant mitochondrial membrane potential reduction and cell apoptosis. These NPs could selectively accumulate at the tumor site of H22 tumor-bearing mice and were detected with the help of ICG fluorescence; moreover, they retarded tumor growth better than monotherapy. Thus, USILA NPs can realize the targeted delivery of dual drugs and the integration of diagnosis and treatment. Moreover, the effects were more significant after co-administration of iRGD peptide, a tumor-penetrating peptide with better penetration promoting ability or programmed cell death ligand 1 (PD-L1) antibody for the reversal of the immunosuppressive state in the tumor microenvironment. The tumor inhibition rates of USILA NPs + iRGD peptide or USILA NPs + PD-L1 antibody with good therapeutic safety were 72.38 % and 67.91 % compared with control, respectively. Overall, this composite nanosystem could act as a promising targeted tool and provide an effective intervention strategy for enhanced HCC synergistic treatment.

Serum uric acid and risk of diabetic neuropathy: a genetic correlation and mendelian randomization study.

Background: Previous observational studies have indicated an association between serum uric acid (SUA) and diabetic neuropathy (DN), but confounding factors and reverse causality have left the causality of this relationship uncertain. Methods: Univariate Mendelian randomization (MR), multivariate MR and linkage disequilibrium score (LDSC) regression analysis were utilized to assess the causal link between SUA and DN. Summary-level data for SUA were drawn from the CKDGen consortium, comprising 288,648 individuals, while DN data were obtained from the FinnGen consortium, with 2,843 cases and 271,817 controls. Causal effects were estimated primarily using inverse variance weighted (IVW) analysis, supplemented by four validation methods, with additional sensitivity analyses to evaluate pleiotropy, heterogeneity, and result robustness. Results: The LDSC analysis revealed a significant genetic correlation between SUA and DN (genetic correlation = 0.293, P = 2.60 × 10-5). The primary methodology IVW indicated that each increase of 1 mg/dL in SUA would increase DN risk by 17% (OR = 1.17, 95% CI 1.02-1.34, P = 0.02), while no causal relationship was found in reverse analysis (OR = 1.00, 95% CI 0.98~1.01, P = 0.97). Multivariate MR further identified that the partial effect of SUA on DN may be mediated by physical activity, low density lipoprotein cholesterol (LDL-C), insulin resistance (IR), and alcohol use. Conclusion: The study establishes a causal link between elevated SUA levels and an increased risk of DN, with no evidence for a reverse association. This underscores the need for a comprehensive strategy in DN management, integrating urate-lowering interventions with modulations of the aforementioned mediators.