Performance and preference of larval parasitoid, Microplitis pallidipes (Hymenoptera: Braconidae), on 2 Spodoptera pest species.

Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae) and Spodoptera litura (Fabricius) are the main pests on corn (Poaceae: Gramineae). The performance of the larval wasp, Microplitis pallidipes Szépligeti (Hymenoptera: Braconidae), was reported on S. frugiperda and S. litura. In this study, we evaluated host selectivity, constructed an age-stage, 2-sex life table, and assessed the pest control potential of M. pallidipes against these 2 pests under laboratory conditions. In a 2-choice host preference experiment, M. pallidipes exhibited a stronger preference for S. frugiperda over S. litura and a distinct preference for second instars. We also investigated the parasitism of females that were either unfed or fed with 10% honey-water solution under different host densities and found that the highest parasitism rate was observed when M. pallidipes were fed with honey-water solution on the first day after mating and a presented female wasp:host ratio of 1:90. In a nonselective assay, M. pallidipes successfully completed a full generation on both hosts. However, the parasitoids exhibited higher fitness and population growth potential when reared on S. frugiperda, with a net reproductive rate (R0) of 24.24, an intrinsic rate of increase (r) of 0.20 per day, a finite rate of increase (λ) of 1.23 per day, and a mean generation time (T) of 15.69 days. This study elucidates the performance of M. pallidipes on 2 Spodoptera host species and offers insights into its biological control potential on lepidopteran pests.

Development and validation of a nomogram for pneumonia risk in burn patients with inhalation injury: a multicenter retrospective cohort study.

BACKGROUND: Burn patients with inhalation injury are at higher risk of developing pneumonia, and yet there is no reliable tool for the assessment of the risk for such patients at admission. This study aims to establish a predictive model for pneumonia risk for burn patients with inhalation injury based on clinical findings and laboratory tests. METHOD: This retrospective study enrolled 546 burn patients with inhalation injury. They were grouped into a training cohort and a validation cohort. The least absolute shrinkage and selection operator (LASSO) regression analysis and binary logistic regression analysis were utilized to identify risk factors for pneumonia. Based on the factors, a nomogram for predicting pneumonia in burn patients with inhalation injury was constructed. Areas under the receiver operating characteristic curves (AUC), calibration plots, and decision curve analysis (DCA) were used to evaluate the efficiency of the nomogram in both the training and validation cohorts. RESULTS: The training cohort included 432 patients, and the validation cohort included 114 patients, with a total of 225 (41.2%) patients experiencing pneumonia. Inhalation injury, tracheal intubation/tracheostomy, low serum albumin, and high blood glucose were independent risk factors for pneumonia in burn patients with inhalation injury and they were further used to build the nomogram. The AUC of the nomogram in the training and validation cohorts were 0.938 (95% CI: 0.917-0.960) and 0.966 (95% CI: 0.931-1), respectively. The calibration curve for probability of pneumonia showed optimal agreement between the prediction by nomogram and the actual observation, and the DCA indicated that the constructed nomogram conferred high clinical net benefit. CONCLUSION: This nomogram can accurately predict the risk of developing pneumonia for burn patients with inhalation injury, and help professionals to identify high-risk patients at an early stage as well as to make informed clinical decisions.

Selenomethionine in gelatin methacryloyl hydrogels: Modulating ferroptosis to attenuate skin aging.

During skin aging, the degeneration of epidermal stem cells (EpiSCs) leads to diminished wound healing capabilities and epidermal disintegration. This study tackles this issue through a comprehensive analysis combining transcriptomics and untargeted metabolomics, revealing age-dependent alterations in the Gpx gene family and arachidonic acid (AA) metabolic networks, resulting in enhanced ferroptosis. Selenomethionine (Se-Met) could enhance GPX4 expression, thereby assisting EpiSCs in countering AA-induced mitochondrial damage and ferroptosis. Additionally, Se-Met demonstrates antioxidative characteristics and extensive ultraviolet absorption. For the sustained and controllable release of Se-Met, it was covalently grafted to UV-responsive GelMA hydrogels via AC-PEG-NHS tethers. The Se-Met@GelMA hydrogel effectively accelerated wound healing in a chronological aging mice model, by inhibiting lipid peroxidation and ferroptosis with augmented GPX4 expression. Moreover, in a photoaging model, this hydrogel significantly mitigated inflammatory responses, extracellular matrix remodeling, and ferroptosis in UV-exposed mice. These characteristics render Se-Met@GelMA hydrogel valuable in practical clinical applications.

Highly efficient and durable planar carbon-based perovskite solar cells enabled by polystyrene modified hole-transporting layers.

The efficiency and durability of perovskite solar cells (PSCs) are closely related to the property and stability of each functional layer involved in device. Owing to the excellent hole transport properties, the additive-doped Spiro-OMeTAD (2,2',7,7'-tetrakis (N,N-di-p-methoxyphenylamine) 9,9'-spirobifluorene) has become an excellent hole-transporting material for obtaining highly efficient PSCs. However, the hygroscopic nature of additives and the pinholes caused by poor film-forming capability inevitably impair the performance and long-term stability of Spiro-OMeTAD and the resulting PSCs. In this study, the hydrophobic polymer polystyrene (PS) was incorporated to improve the hydrophobicity and film-forming capability of the additive-doped Spiro-OMeTAD films. Based on the PS-modified Spiro-OMeTAD and carbon electrodes, the derived planar carbon-based PSCs exhibited significantly enhanced long-term stability, which can maintain 92% of its initial efficiency after aging for 2500 h under ambient atmosphere without encapsulation. In addition, the PS-modified Spiro-OMeTAD exhibited improved morphology with reduced pinholes, contributing to significantly enhanced interfacial carrier transport. Finally, a champion power conversion efficiency of 21.06% was obtained, which is one of the highest efficiencies reported for the planar carbon-based PSCs to date.

A study on the preoperative risk factors for primary healing failure in the reconstruction of deep sternal wound infection with platelet-rich plasma and negative pressure trauma therapy.

Deep sternal wound infection (DSWI) is a relatively complex wound in wound reconstruction surgery. Because plastic surgeons deal with DSWI patients late. The primary healing (healing by first intention) after reconstruction of DSWI is restricted by many preoperative risk factors. The purpose of this study is to explore and analyse the risk factors of primary healing failure in patients with DSWI treated with platelet-rich plasma (PRP) and negative pressure trauma therapy (NPWT). 115 DSWI patients treated with the PRP and NPWT (PRP + NPWT) modality were retrospectively (2013-2021) analysed. They were divided into two groups according to primary healing results after the first PRP + NPWT treatment. Univariate and multivariate analyses were used to compare the data of the two groups to find out the risk factors and their optimal cut-off values were identified by ROC analysis. The primary healing results, debridement history, wound size, sinus, osteomyelitis, renal function, bacterial culture, albumin (ALB), platelet (PLT) between the two groups were significantly different (P < 0.05). Binary logistic regression showed that osteomyelitis, sinus, ALB and PLT were the risk factors affecting primary healing outcomes (P < 0.05). ROC analysis showed that AUC for ALB in the non-primary healing group was 0.743 (95% CI: 0.650-0.836, P < 0.05) and its optimal cutoff value of 31 g/L was associated with primary healing failure with a sensitivity of 96.9% and specificity of 45.1%. AUC for PLT in the non-primary healing group was 0.670 (95% CI: 0.571 ~ 0.770, P < 0.05) its optimal cutoff value of 293 × 109 /L was associated with primary healing failure with a sensitivity of 72.5% and specificity of 56.3%. In the cases included in this study, the success rate of primary healing of DSWI treated with PRP + NPWT was not affected by the most common preoperative risk factors for wound non-union. It is indirectly confirmed that PRP + NPWT is an ideal treatment. However, it should be noted that it will still be adversely affected by sinus osteomyelitis, ALB and PLT. The patients need to be carefully evaluated and corrected before reconstruction.

Transcriptome analysis of hepatic injury caused by delayed resuscitation following severe burns in rats.

BACKGROUND: Delayed resuscitation (DR) can induce hepatic reperfusion injury after severe burns. The underlying molecular mechanisms of DR-induced hepatic injury remain unidentified. This study sought to predict candidate genes and molecular pathways in a DR-induced hepatic injury preclinical model. METHODS: Rats were randomized into three groups: the sham injury (Sham) group; the DR group, which had third-degree burns covering 30% of the body surface area and DR; and the early resuscitation (ER) group, in which ER was administered. The liver tissue was harvested for the purpose of evaluating hepatic injury and performing transcriptome sequencing. Differentially expressed genes (DEGs) for DR versus Sham and ER versus DR were analyzed respectively. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Ingenuity Pathway Analysis were used. The DEGs and critical module genes were intersected to obtain critical genes. Immune infiltration and competing endogenous RNA networks were also analyzed. Validation was conducted using quantitative real-time polymerase chain reaction. RESULTS: Hepatic injury was evident in DR rats. There were 2,430 DEGs between DR and Sham and 261 DEGs between ER and DR. Differentially expressed genes were mostly enriched in metabolic process for DR versus Sham, and immune and inflammatory processes for ER versus DR. Four critical genes (Tff3, C1galt1, Cd48, and MGC105649) were obtained by screening. Five immune cells were significantly different between DR and Sham, and seven immune cells were significantly different between ER and DR in immunoassays. Three critical genes, 75 miRNAs, 7 lncRNAs, and 197 edges constituted the mRNA-miRNA-lncRNA linkages, which included C1galt1-rno-miR-330-5p-Pvt1, among others. CONCLUSION: This is the first attempt to perform a high-throughput analysis of gene expression profiles in DR-induced hepatic injury. It shows that immunity and inflammation-related RNAs and pathways play an important role in the progression of hepatic injury. It also provides insight into some important RNAs and regulatory targets related to disease.

Critical Sites of Serine Acetyltransferase in Lathyrus sativus L. Affecting Its Enzymatic Activities.

LsSAT2 (serine acetyltransferase in Lathyrus sativus) is the rate-limiting enzyme in biosynthesis of ß-N-oxalyl-l-α,ß-diaminopropionic acid (ß-ODAP), a neuroactive metabolite distributed widely in several plant species including Panax notoginseng, Panax ginseng, and L. sativus. The enzymatic activity of LsSAT2 is post-translationally regulated by its involvement in the cysteine regulatory complex in mitochondria via interaction with ß-CAS (ß-cyanoalanine synthase). In this study, the binding sites of LsSAT2 with the substrate Ser were first determined as Glu290, Arg316, and His317 and the catalytic sites were determined as Asp267, Asp281, and His282 via site-directed/truncated mutagenesis, in vitro enzymatic activity assay, and functional complementation of the SAT-deficient Escherichia coli strain JM39. Furthermore, the C-terminal 10-residue peptide of LsSAT2 is confirmed to be critical to interact with LsCAS, and Ile336 in C10 peptide is the critical amino acid. These results will enhance our understanding of the regulation of LsSAT2 activities and the biosynthesis of ß-ODAP in L. sativus.

Review on risk factors, classification, and treatment of sternal wound infection.

Sternal wound infection (SWI) is the most common complication of the median sternal incision. The treatment time is long, and the reconstruction is difficult, which causes challenges for surgeons. Plastic surgeons were often involved too late in such clinical scenarios when previous empirical treatments failed and the wound damage was relatively serious. Accurate diagnosis and risk factors against sternal wound infection need to be in focus. Classification of different types of sternotomy complications post-cardiac surgery is important for specific categorization and management. Not familiar with this kind of special and complex wound, objectively increasing the difficulty of wound reconstruction. The purpose of this comprehensive review is to review the literature, introduce various SWI risk factors related to wound nonunion, various classification characteristics, advantages and disadvantages of various wound reconstruction strategies, to help clinicians understand the pathophysiological characteristics of the disease and choose a better treatment method.

The application of the Limberg flap repair technique in the surgical treatment of pilonidal sinus disease.

Pilonidal sinus disease (PNSD) challenged surgeons for decades. Limberg flap repair (LFR) is a common treatment for PNSD. The purpose of this study was to observe the effect and risk factors of LFR in PNSD. A retrospective study was conducted on the PNSD patients who visited two medical centers and four departments in the People's Liberation Army General Hospital and were taking LFR treatment between 2016 and 2022. The risk factors, the effect of the operation, and complications were observed. The effects of known risk factors on the surgical results were compared. There were 37 PNSD patients: male/female ratio of 35:2, average age: 25.1 ± 7.9 years. Average BMI: 25.2 ± 4.0 kg/m2 , average wound healing time: 15.4 ± 3.4 days. 30 patients (81.0%) healed in stage one and 7 (16.3%) had postoperative complications. Only 1 patient (2.7%) had a recurrence while others were healed after dressing-changing. There was no significant difference in age, BMI, preoperative debridement history, preoperative sinus classification, Wound area, Negative pressure drainage tube, prone time (<3d) and treatment effect. Squat defecate and premature defecation were associated with treatment effect, and they were independent predictors of treatment effect in the multivariate analysis. LFR has a stable therapeutic outcome. Compared with other skin flaps, the therapeutic effect of this flap is not significantly different, but the design is simple and is not affected by the known risk factors before operation. However, it is necessary to avoid the influence of two independent risk factors, squatting defecation and premature defecation, on the therapeutic effect.

Within-patient randomised clinical trial exploring the development of microskin implantation in the treatment of pressure ulcers.

Pressure injury often seriously affects the life quality of aged patients, especially the long-term bedridden casualties. Widely adopted by different disciplines, negative pressure suction has its role in pressure injury. Microskin implantation has been demonstrated powerful in increasing the expansion ratio of donor area-derived skin and accelerating wound healing by forming "skin islands". The study was designed to evaluate the efficacy and safety of additional use of bedside microskin implantation in the palliative care of pressure injury of aged patients who cannot tolerate surgical treatment as a supplement for standard negative pressure suction. An open-label within-patient RCT was conducted in aged patients with pressure injury. Sixteen patients were enrolled. After granulation tissues formed, half of a pressure injury was randomised to receive the negative pressure suction as the control group, and the other half exposed to additional bedside microskin implantation as the experimental group. Efficacy was evaluated within 1 month after treatment, and the primary endpoints included the wound healing rate and pressure ulcer scale for healing (PUSH) scores. The secondary outcomes included survival rate of implanted microskin, pain intensity assessment, satisfaction surveys from patients or their family, and pressure ulcer healing complications. Sixteen patients completed the study. After 14 days of operation, 5.63 ± 1.78 out of 10 pieces of implanted microskin survived and formed neonatal epithelium. The wound healing rates of the control group and the experimental group at 1 month were (26.17 ± 9.03%) and (35.95 ± 16.02%), respectively (P < .01). The mean PUSH score before the surgery was 12.38 ± 2.23. At 1 month after surgery, the mean difference of PUSH score from baseline was 2.13 ± 0.96 in the control group and 2.81 ± 0.83 in the experimental group (P < .01). The treatment of microskin implantation did not cause additional pain or complications to the patients. Accompanied by a better ulcer status, the majority of patients or their guardians have a high degree of acceptance towards the microskin implantation. Bedside microskin implantation could accelerate wound healing with lower PUSH scores. As a complementary palliative treatment, supplementary microskin implantation is effective and well tolerated.

Transcriptome reveals the dysfunction of pancreatic islets after wound healing in severely burned mice.

BACKGROUND: Severely burned patients have a higher risk of diabetes mellitus after healing, but its mechanism remains unclear. Therefore, the purpose of the study was to explore the influence of burns on pancreatic islets of mice after wound healing. METHODS: Forty-two male C57BL/6 mice were randomized into a sham group and a burn group and subjected to sham treatment or a third-degree burn model of 30% total body surface area. Fasting blood glucose was detected weekly for 8 weeks after severe burns. Glucose-stimulated insulin secretion was measured 8 weeks post severe burns. Islets of the two groups were isolated and mRNA libraries were sequenced by the Illumina sequencing platform. The expressions of differentially expressed genes (DEGs) related to the cell cycle and the amounts of mitochondrial DNA were detected by quantitative real-time polymerase chain reaction after gene ontology, gene set enrichment analysis, and protein-protein network analysis. Hematoxylin-eosin staining of pancreatic tail tissue and adenosine triphosphate (ATP) assay of islets were performed. RESULTS: The levels of fasting blood glucose were significantly higher within 8 weeks post severe burns. Glucose-stimulated insulin secretion was impaired at the eighth week post severe burns. Totally 128 DEGs were selected. Gene ontology and gene set enrichment analysis indicated that the pathways related to the cell cycle, protein processing, and oxidative phosphorylation were downregulated. The expressions of DEGs related to the cell cycle showed a consistent trend with mRNA sequencing data, and most of them were downregulated post severe burns. The cell mass of the burn group was less than that of the sham group. Also, the concentration of ATP and the amount of mitochondrial DNA were lower in the burn group. CONCLUSION: In the model of severe-burned mice, disorders in glucose metabolism persist for 8 weeks after burns, which may be related to low islet cell proliferation, downregulation of protein processing, and less ATP production.

Yeast Diversity during Spontaneous Fermentations and Oenological Characterisation of Indigenous Saccharomyces cerevisiae for Potential as Wine Starter Cultures.

Diversity of regional yeast can be influenced by geography, grape cultivars and the use of SO2, but at single vineyard scale in China, the impact of these factors on yeast population, particularly Saccharomyces cerevisiae, is not well studied. Here, we characterised yeast species and dynamics during spontaneous fermentations with/without SO2 using eight typical grape cultivars from Yuma vineyard in Ningxia wine region of China. Results show that distribution and abundance of yeast species varied by grape varieties, fermentation stage and SO2 treatment. A number of 290 S. cerevisiae isolates were further classified into 33 genotypes by Interdelta fingerprinting. A prevailing role of grape varieties in shaping the genetic divergence of S. cerevisiae in Yuma vineyard was observed, as compared to the impacts of fermentation stage and SO2 treatment. Pre-selected S. cerevisiae strains were subjected to vinification with Cabernet Sauvignon and Chardonnay. All strains completed fermentations but the physiochemical parameters and volatile profiles of wines were strain-specific. Some indigenous S. cerevisiae yielded more desirable aroma compounds compared to the commercial strains, among which NX16 and NX18 outcompeted others, therefore having potential for use as starters. This study provides comprehensive analysis on yeast diversity at vineyard scale in Ningxia. Information on the vinification using indigenous S. cerevisiae is of great value for improving Ningxia wine regionality.

Preparation of the Carbonized Zif-8@PAN Nanofiber Membrane for Cadmium Ion Adsorption.

The zeolitic imidazolate framework (ZIF-8)@polyacrylonitrile (PAN) nanofiber membrane was prepared and carbonized for heavy metal cadmium ion (Cd2+) adsorption in aqueous medium. Zinc oxide (ZnO) was first sputtered onto the surface of the PAN electrospun nanofiber membrane to provide a metal ion source. Then, the ZIF-8@PAN nanofiber membrane was prepared via in situ solvothermal reaction and carbonized in a tube furnace at 900 °C under a N2 atmosphere to enhance adsorption performance. The synthesized ZIF-8 particles with polyhedral structure were uniformly immobilized on the surface of the PAN electrospun nanofiber membrane. After being heated at 900 °C, the polygonal ZIF-8 shrank, and the carbonized ZIF-8@PAN nanofiber membrane was obtained. Compared with the nanofiber membrane without being carbonized, the adsorption capacity of the carbonized ZIF-8@PAN nanofiber membrane reached 102 mg L-1, and its Cd2+ adsorption efficiency could be more than 90% under the adsorption temperature of 35 °C and solution of pH = 7.5 conditions. According to the adsorption thermodynamics analysis, the Cd2+ adsorption process of the carbonized ZIF-8@PAN nanofiber membrane was spontaneous. The whole Cd2+ adsorption process was more suitably described by the pseudo second-order adsorption kinetics model, indicating that there exists a chemical adsorption mechanism besides physical adsorption.

Nicotinamide mononucleotide promotes pancreatic islet function through the SIRT1 pathway in mice after severe burns.

OBJECTIVE: The high levels of oxidative stress and apoptosis of pancreatic islet cells after severe burns lead to the dysfunction of islets and glucose metabolism disorders. Silent information regulator of transcription 1 (SIRT1) can decrease oxidative stress and apoptosis of islets in diabetes mellitus. This study aimed to investigate the role of SIRT1 on pancreatic islets and whether nicotinamide mononucleotide (NMN) can impact the function of pancreatic islets after severe burns. METHODS: A 30% total body surface area full-thickness burn model was established using male C57BL/6 mice, and mice were randomized into sham group, burn group, burn + NMN group and burn + NMN + EX-527 group. The concentration of nicotinamide adenine dinucleotide (NAD), the expression of SIRT1, apoptosis induction, mitochondrial function and related signalling pathways of pancreatic islets at 24 h after severe burns were tested. RESULTS: Severe burns led to decreased NAD level and SIRT1 expression of pancreatic islets, increased apoptosis rate, and mitochondrial dysfunction of pancreatic islets. NAD repletion by NMN and upregulation of SIRT1 expression reduced the phosphorylation and acetylation levels of NF-κB p65 and burn-induced apoptosis. Meanwhile, the mitochondrial function of islets was rescued by NMN treatment through the SIRT1/UCP2 axis and SIRT1/PGC1-α axis. In addition, the fasting blood glucose decreased and glucose-stimulated insulin secretion was improved with NMN treatment after severe burns. This protective effect of NMN could be abolished by EX-527, the inhibitor of SIRT1. CONCLUSION: NMN can increase the concentration of NAD+ of pancreatic islets and regulate SIRT1 and its downstream targets, thereby reducing apoptosis, maintaining mitochondrial function and improving pancreatic islet function after severe burn injury.

Screening and diagnosis of triple negative breast cancer based on rapid metabolic fingerprinting by conductive polymer spray ionization mass spectrometry and machine learning.

We present the use of conductive spray polymer ionization mass spectrometry (CPSI-MS) combined with machine learning (ML) to rapidly gain the metabolic fingerprint from 1 µl liquid extraction from the biopsied tissue of triple-negative breast cancer (TNBC) in China. The 76 discriminative metabolite markers are verified at the primary carcinoma site and can also be successfully tracked in the serum. The Lasso classifier featured with 15- and 22-metabolites detected by CPSI-MS achieve a sensitivity of 88.8% for rapid serum screening and a specificity of 91.1% for tissue diagnosis, respectively. Finally, the expression levels of their corresponding upstream enzymes and transporters have been initially confirmed. In general, CPSI-MS/ML serves as a cost-effective tool for the rapid screening, diagnosis, and precise characterization for the TNBC metabolism reprogramming in the clinical practice.

Evaluating the higher education productivity of Chinese and European "elite" universities using a meta-frontier approach.

This research focuses on a sample of European and Chinese elite universities for the period 2011-2015. We adopt a meta-frontier methodology to decompose their overall productivity in three main determinants: (1) technical efficiency compared with contemporaneous technology, (2) change in technical efficiency and (3) technology relative superiority of the two groups of universities. The results reveal different patterns of evolution: Chinese institutions' productivity grows faster than that of their European counterparts (+ 7.15%/year vs 4.51%/year), however the latter maintain a higher level of technology in efficient production as a group.

Discovery of a Candidate Containing an (S)-3,3-Difluoro-1-(4-methylpiperazin-1-yl)-2,3-dihydro-1H-inden Scaffold as a Highly Potent Pan-Inhibitor of the BCR-ABL Kinase Including the T315I-Resistant Mutant for the Treatment of Chronic Myeloid Leukemia.

BCR-ABL kinase inhibition is an effective strategy for the treatment of chronic myeloid leukemia (CML). Herein, we report compound 3a-P1, bearing a difluoro-indene scaffold, as a novel potent pan-inhibitor against BCR-ABL mutants, including the most refractory T315I mutant. As the privileged (S)-isomer compared to its (R)-isomer 3a-P2, 3a-P1 exhibited potent antiproliferative activities against K562 and Ku812 CML cells and BCR-ABL and BCR-ABLT315I BaF3 cells, with IC50 values of 0.4, 0.1, 2.1, and 4.7 nM, respectively. 3a-P1 displayed a good safety profile in a battery of assays, including single-dose toxicity, hERG K+, and genotoxicity. It also showed favorable mice pharmacokinetic properties with a good oral bioavailability (32%), a reasonable half-life (4.61 h), and a high exposure (1386 h·ng/mL). Importantly, 3a-P1 demonstrated a higher potency than ponatinib in a mice xenograft model of BaF3 harboring BCR-ABLT315I. Overall, the results indicate that 3a-P1 is a promising drug candidate for the treatment of CML to overcome the imatinib-resistant T315I BCR-ABL mutation.

ß-Cyanoalanine Synthase Regulates the Accumulation of ß-ODAP via Interaction with Serine Acetyltransferase in Lathyrus sativus.

ß-N-Oxalyl-l-α,ß-diaminopropionic acid (ß-ODAP), found in Lathyrus sativus at first, causes a neurological disease, lathyrism, when over ingested in an unbalanced diet. Our previous research suggested that ß-ODAP biosynthesis is related to sulfur metabolism. In this study, ß-cyanoalanine synthase (ß-CAS) was confirmed to be responsible for ß-ODAP biosynthesis via in vitro enzymatic analysis. LsCAS was found to be pyridoxal phosphate (PLP)-dependent via spectroscopic analysis and dual functional via enzymatic activity analysis. Generation of a M135T/M235S/S239T triple mutant of LsCAS, which are the key sites to control the ratio of CAS/cysteine synthase (CS) activity, switches reaction chemistry to that of a CS. LsCAS interactions were further screened and verified via Y2H, BiFC and pull-down assay. It was suggested that LsSAT2 interacts and forms a cysteine regulatory complex (CRC) with LsCAS in mitochondria, which improves LsSAT while reduces LsCAS activities to affect ß-ODAP content positively. These results provide new insights into the molecular regulation of ß-ODAP content in L. sativus.

AIM2 promotes the development of non-small cell lung cancer by modulating mitochondrial dynamics.

Mitochondrial fusion and fission dynamics fine-tune cellular calcium homeostasis, ATP production capacity and ROS production and play important roles in cell proliferation and migration. Dysregulated mitochondrial dynamics is closely related to tumor development, but the mechanism of mitochondrial dynamics dysregulation and its role in the development of lung cancer remains unclear. Here, we demonstrate that the DNA sensor protein absent in melanoma 2 (AIM2) is highly expressed in non-small cell lung cancer (NSCLC) cells and that high AIM2 expression is associated with poor prognosis in patients with NSCLC. High expression of AIM2 contributes to tumor cell growth and proliferation independent of inflammasome activation in vitro and in vivo. Further studies have shown that AIM2 colocalizes with mitochondria in NSCLC cells and that AIM2 knockdown leads to enhanced mitochondrial fusion and decreased cell proliferation. Mechanistic studies have shown that AIM2 downregulation promotes MFN2 upregulation, thereby enhancing mitochondrial fusion. Moreover, we found that mitochondrial fusion driven by AIM2 knockdown leads to a decrease of cellular reactive oxygen species (ROS) production, which further causes inactivation of the MAPK/ERK signaling pathway. Together, we discovered a novel function of AIM2 in promoting NSCLC development by regulating mitochondrial dynamics and revealed its underlying mechanism. Our work provides new intervention targets for the treatment of NSCLC.

[Protective effects of Shenmai injection on intestinal mucosal barrier function in severely scalded rats].

OBJECTIVE: To investigate the protective effects of shen-mai injection on intestinal barrier function in the early stage of 30% 3° scald, and to provide experimental basis for the prevention and control of enterogenic infection. METHODS: A total of 60 Wistar rats were randomly divided into 6 groups: normal control group (without treatment), model control group (with 30% total body surface area (TBSA) fully thickness burn on the back), hexadecadrol (5 mg/kg) group, Shenmai injection (5, 10, 15 mg/kg) groups, with 10 rats in each group. After burned by scald apparatus, rats in each group were treated with drugs immediately by intraperitoneal injection once a day. At 72 hours after burned, the levels of plasma endotoxin, diamine oxidase (DAO), tumor necrosis factor-alpha (TNF-α), interleukins-6(IL-6) in all rats were detected and the mesenteric lymph nodes, liver and spleen were homogenized to culture for bacteria. The change of secretory immunoglobulin A (sIgA) in intestinal mucosa was measured. RESULTS: Compared with normal control group, bacterial translocation quantity in mesenteric lymph nodes(MLN), liver, and spleen, and the plasma levels of DAO, endotoxin, TNF-α, IL-6 and the level of sIgA in intestinal mucosa in model control group were increased significantly (P＜0.01); compared with model control group, bacterial translocation quantity in MLN, liver, and spleen, and the plasma levels of DAO, endotoxin, TNF-α, IL-6 and the level of sIgA in intestinal mucosa in hexadecadrol (5 mg/kg) group and shen-mai injection (5, 10, 15 mg/kg) groups were decreased significantly (P＜0.05 or P＜0.01). CONCLUSION: Shen-mai injection can alleviate intestinal mucosa injury caused by severe scald, and the effects are similar with those of dexamethasone, and the effect is better in the high-dose group.