Jasmonic acid (JA), a plant endogenously synthesized lipid hormone, plays an important role in response to stress. This manuscript summarized the biosynthesis and metabolism of JA and its related regulatory mechanisms, as well as the signal transduction of JA. The mechanism and regulatory network of JA in plant response to biotic and abiotic stresses were systematically reviewed, with the latest advances highlighted. In addition, this review summarized the signal crosstalk between JA and other hormones in regulating plant resistance to various stresses. Finally, the problems to be solved in the study of plant stress resistance mediated by JA were discussed, and the application of new molecular biological technologies in regulating JA signaling to enhance crop resistance was prospected, with the aim to facilitate future research and application of plant stress resistance.
Signal Transduction ; Cyclopentanes ; Oxylipins ; Plant Growth Regulators

Objective To observe the effect of canagliflozin combined with enalapril on diabetic nephropathy(DN).Methods DN patients were randomly divided into control group and treatment group.All patients in 2 groups received basic treatment of recombinant human insulin injection,and the control group was orally administered enalapril tablet 10 mg(qd).The treatment group was given orally canagliflozin tablet 100 mg(qd)on the basis of the control group.Both groups were treated for 8 weeks.Renal function,blood glucose index,serum vascular endothelial growth factor(VEGF),transforming growth factor-β(TGF-β),homocysteine(HCY)levels,clinical efficacy and incidence of adverse drug reactions were compared between 2 groups.Results There were 71 cases were included in the control group and 73 cases in the treatment group.After treatment,β2 microglobulin(β2-MG)in treatment group and control group were(0.21±0.03)and(0.28±0.04)mg·L-1;blood urea nitrogen(BUN)were(4.23±0.42)and(5.58±0.65)mmol·L-1;serum creatinine(SCr)were(89.32±8.29)and(101.25±10.18)pmol·L-1;24 h microalbumin(mAlb)were(49.38±5.06)and(58.21±6.43)mg;glycosylated hemoglobin(HbA1c)were(6.10±0.11)％and(6.45±0.16)％;2 h postprandial blood glucose levels were(6.05±0.78)and(7.68±1.82)mmol·L-1;fasting blood glucose(FBG)were(5.02±0.32)and(5.67±0.65)mmol·L-1;VEGF levels were(350.18±20.04)and(389.04±24.16)pg·mL-1;TGF-β were(148.32±16.57)and(168.24±20.02)pg·mL-1;HCY were(13.12±2.38)and(19.35±3.21)pmol·L-1,the differences were statistically significant(all P＜0.05).After treatment,the total effective rate of treatment group and control group were 83.56％(61 cases/73 cases)and 67.61％(48 cases/71 cases),the difference was statistically significant(P＜0.05).The total incidence of adverse drug reactions in treatment group and control group were 6.85％and 4.23％,with no significant difference(P＞0.05).Conclusion Canagliflozin combined with enalapril is effective in the treatment of diabetic nephropathy,which can improve renal function,regulate blood glucose metabolism,and down-regulate serum VEGF,TGF-β and HCY levels,and is safe and reliable.

Objective To observe the clinical efficacy and safety of rituximab injection combined with leflunomide tablets in the treatment of patients with systemic lupus erythematosus(SLE).Methods The SLE patients were divided into control and treatment groups according to cohort method.The control group received leflunomide with 50 mg·d-1 after meal in the first 3 days of treatment and was adjusted to 20 mg·d-1 thereafter.On the basis of control group,the treatment group was combined with rituximab,375 mg·m-2 was given intravenously every 2 weeks in the first 3 times of treatment,and adjusted to once every 4 weeks from the 4th dose.Two groups were treated for 24 weeks.The clinical efficacy,systemic lupus erythematosus disease activity index(SLEDAI)scores,serological indicators,24-hour urinary protein and adverse drug reactions were compared between two groups.Results The treatment and control groups were enrolled 74 cases and 72 cases,respectively.After treatment,the total effective rates of treatment and control groups were 91.89％(68 cases/74 cases)and 79.17％(57 cases/72 cases)with significant difference(P＜0.05).After treatment,the SLEDAI scores of treatment and control groups were(7.21±1.67)and(9.03±1.35)points;the levels of anti-Smith/ribonucleoprotein antibodies were(81.43±18.25)and(59.38±14.61)U·mL-1;the levels of immunoglobulin G were(12.04±2.15)and(17.28±2.64)g·L-1;the levels of interleukin-10 were(33.39±7.13)and(39.87±9.02)pg·mL-1;24-hour urinary protein quantification were(1.46±0.32)and(2.67±0.54)g·24 h-1;all the differences were statistically significant(all P＜0.05).The drug adverse reactions of two groups were liver and kidney function injury and digestive tract reactions.The total incidences of drug adverse reactions in the treatment and control groups were 13.51％and 5.56％without significant difference(P＞0.05).Conclusion Rituximab injection combined with leflunomide tablets has a definitive clinical efficacy in the treatment of SLE patients,which can significantly reduce disease activity and inflammatory reactions,improve immune function,without increasing the incidence of drug adverse reactions.

Localized scleroderma (LoS) is a chronic autoimmune skin disorder characterized by fibrosis and hardening of the skin and subcutaneous tissues, potentially affecting deeper tissues and other organs. Currently, China lacks evidence-based guidelines for the diagnosis and management of LoS, which poses a challenge to disease recognition and leads to significant variation in treatment strategies across medical centers. To address this problem, we plan to establish a nationwide, multidisciplinary expert team through the Chinese Society of Plastic Surgery to initiate the development of the Chinese Guideline for the Diagnosis and Management of Localized Scleroderma. The guideline aims to standardize the diagnosis and treatment procedures for LoS, improve clinical diagnostic and therapeutic capabilities, and enhance patient outcomes through early identification and intervention. The guideline will adhere to international standards, with recommendations formed through evidence evaluation and multiple rounds of expert discussions. Although evidence-based data on LoS specific to the Chinese population is currently limited, and no unified gold standard for disease assessment exists, the clinical expertise of multidisciplinary specialists will play a pivotal role in the guideline's formulation. We anticipate that this guideline will provide LoS patients with higher-quality medical care and enhance patient awareness and engagement, which may ultimately help reduce social and healthcare burden. This proposal outlines the background, methodology, and anticipated value of the guideline, with the hope of providing guidance for its rigorous development and successful publication.

Objective To investigate the molecular mechanism of sulforaphane(Sul)promoting bone marrow stem cells(BMSCs)differentiating into osteoblasts.Methods BMSCs were divided into the control group(without any treatment),induction group(induction of osteogenic differentiation),and induction+Sul group(induction of osteogenic differentiation with the addition of 40 μmol/L of Sul).The adenovirus-shRNA-Mock,-shRNA-TET1,-shRNA-TET2,and-shRNA-TET3 were transfected into BMSCs as the shRNA-Mock group,shRNA-TET1 group,shRNA-TET2 group,and shRNA-TET3 group.BMSCs were cultured in cell culture medium containing osteogenic differentiation induction medium and 40 μmol/L of Sul,and then transfected with adenovirus-shRNA-TET1,-shRNA-TET2,-shRNA-TET3,and-shRNA-Mock as the induction+Sul+shRNA-TET1 group,induction+Sul+shRNA-TET2 group,induction+Sul+shRNA-TET3 group,and induction +Sul+shRNA-Mock group.The mRNA and protein expression levels of Runx2 after BMSCs differentiated into osteoblasts were determined by qPCR and Western blot.The DNA content of Runx2 promoter region bound to Histone H3 after BMSCs differentiated into osteoblasts was determined by chromatin immunocoprecipitation(ChIP).The methylation level of Runx2 promoter region of BMSCs differentiated into osteoblasts was determined by HpaⅡenzyme and MspⅠenzyme digestion combined with qPCR.The degree of BMSCs differentiated into osteoblasts was determined by alizarin red staining.Results Compared with the induction group,the mRNA and protein expression levels of Runx2 in the induction+Sul group were significantly increased(P<0.05);the content of DNA in the Runx2 promoter region bound to Histone H3 was increased(P<0.05),the methylation level of Runx2 promoter region was reduced(P<0.05),and the alizarin red staining score was elevated(P<0.05).Compared with the induction+Sul group,the content of DNA in the Runx2 promoter region bound to Histone H3 in the induction+Sul+shRNA-TET1 group was decreased(P<0.05),the methylation level of Runx2 promoter region was increased(P<0.05),and the alizarin red staining score was decreased(P<0.05).While there was no significant change among the induction+Sul+shRNA-TET2 group,induction+Sul+shRNA-TET3 group,induction+Sul+shRNA-Mock group(P>0.05).Conclusion Sul can promote the differentiation of BMSCs into osteoblasts through promoting DNA demethylation of Runx2 promoter region by TET1.

PI3Kγ and PI3Kδ have important regulatory roles in the immune system, and targeting these two subtypes helps to reshape the tumor microenvironment. PI3Kγ and PI3Kδ are potential targets for tumor immunotherapy. In this study, a series of new pyrazolopyrimidine derivatives were designed and synthesized on the basis of our previously reported PI3K inhibitors, resulting in the discovery of compound 16l as a potent and selective PI3Kγ/δ dual inhibitor. Compound 16l demonstrated strong biochemical potencies against PI3Kγ and PI3Kδ with IC₅₀ values of 0.11 and 0.79 nmol·L^-1. In cell-based assays, it potently inhibited the PI3Kγ and PI3Kδ mediated Akt S473 phosphorylation with EC₅₀ values of 3 and 7 nmol·L^-1. In vivo, compound 16l exhibited acceptable pharmacokinetic properties in Sprague-Dawley (SD) rats and suppressed the tumor growth in a MC38 syngeneic mouse model. The animal experiments were approved by the Animal Ethics Committee of Hefei Institutes of Physical Science, Chinese Academy of Sciences (approval number: DWLL-2000-06). In addition, no appreciable human ether-a-go-go-related gene (hERG) inhibition was observed for compound 16l even at 30 μmol·L^-1. These results suggested that compound 16l might be a potential research tool for studying the PI3Kγ/δ mediated signaling pathways.

Objective:To investigate the clinical repair strategy for ischial tuberosity pressure ulcers based on the sinus tract condition and range of skin and soft tissue defects.Methods:The study was a retrospective observational study. From July 2017 to March 2023, 21 patients with stage Ⅲ or Ⅳ ischial tuberosity pressure ulcers who met the inclusion criteria were admitted to the First Affiliated Hospital of Nanchang University, including 13 males and 8 females, aged 14-84 years. There were 31 ischial tuberosity pressure ulcers, with an area of 1.5 cm×1.0 cm-8.0 cm×6.0 cm. After en bloc resection and debridement, the range of skin and soft tissue defect was 6.0 cm×3.0 cm-15.0 cm×8.0 cm. According to the depth and size of sinus tract and range of skin and soft tissue defects on the wound after debridement, the wounds were repaired according to the following three conditions. (1) When there was no sinus tract or the sinus tract was superficial, with a skin and soft tissue defect range of 6.0 cm×3.0 cm-8.5 cm×6.5 cm, the wound was repaired by direct suture, Z-plasty, transfer of buttock local flap, or V-Y advancement of the posterior femoral cutaneous nerve nutrient vessel flap. (2) When the sinus tract was deep and small, with a skin and soft tissue defect range of 8.5 cm×4.5 cm-11.0 cm×6.5 cm, the wound was repaired by the transfer and filling of gracilis muscle flap followed by direct suture, or Z-plasty, or combined with transfer of inferior gluteal artery perforator flap. (3) When the sinus tract was deep and large, with a skin and soft tissue defect range of 7.5 cm×5.5 cm-15.0 cm×8.0 cm, the wound was repaired by the transfer and filling of gracilis muscle flap and gluteus maximus muscle flap transfer, followed by direct suture, Z-plasty, or combined with transfer of buttock local flap; and transfer and filling of biceps femoris long head muscle flap combined with rotary transfer of the posterior femoral cutaneous nerve nutrient vessel flap; and filling of the inferior gluteal artery perforator adipofascial flap transfer combined with V-Y advancement of the posterior femoral cutaneous nerve nutrient vessel flap. A total of 7 buttock local flaps with incision area of 8.0 cm×6.0 cm-19.0 cm×16.0 cm, 21 gracilis muscle flaps with incision area of 18.0 cm×3.0 cm-24.0 cm×5.0 cm, 9 inferior gluteal artery perforator flaps or inferior gluteal artery perforator adipofascial flaps with incision area of 8.5 cm×6.0 cm-13.0 cm×7.5 cm, 10 gluteal maximus muscle flaps with incision area of 8.0 cm×5.0 cm-13.0 cm×7.0 cm, 2 biceps femoris long head muscle flaps with incision area of 17.0 cm×3.0 cm and 20.0 cm×5.0 cm, and 5 posterior femoral cutaneous nerve nutrient vessel flaps with incision area of 12.0 cm×6.5 cm-21.0 cm×10.0 cm were used. The donor area wounds were directly sutured. The survival of muscle flap, adipofascial flap, and flap, and wound healing in the donor area were observed after operation. The recovery of pressure ulcer and recurrence of patients were followed up.Results:After surgery, all the buttock local flaps, gracilis muscle flaps, gluteus maximus muscle flaps, inferior gluteal artery perforator adipofascial flaps, and biceps femoris long head muscle flaps survived well. In one case, the distal part of one posterior femoral cutaneous nerve nutrient vessel flap was partially necrotic, and the wound was healed after dressing changes. In another patient, bruises developed in the distal end of inferior gluteal artery perforator flap. It was somewhat relieved after removal of some sutures, but a small part of the necrosis was still present, and the wound was healed after bedside debridement and suture. The other posterior femoral cutaneous nerve nutrient vessel flaps and inferior gluteal artery perforator flaps survived well. In one patient, the wound at the donor site caused incision dehiscence due to postoperative bleeding in the donor area. The wound was healed after debridement+Z-plasty+dressing change. The wounds in the rest donor areas of patients were healed well. After 3 to 15 months of follow-up, all the pressure ulcers of patients were repaired well without recurrence.Conclusions:After debridement of ischial tuberosity pressure ulcer, if there is no sinus tract formation or sinus surface is superficial, direct suture, Z-plasty, buttock local flap, or V-Y advancement repair of posterior femoral cutaneous nerve nutrient vessel flap can be selected according to the range of skin and soft tissue defects. If the sinus tract of the wound is deep, the proper tissue flap can be selected to fill the sinus tract according to the size of sinus tract and range of the skin and soft tissue defects, and then the wound can be closed with individualized flap to obtain good repair effect.

Objective To investigate the effect of evodiamine on renal fibrosis in rats with chronic renal failure(CRF)by regulating sphingosine kinase 1(SphK1)/S1P signaling pathway.Methods CRF rat model was established by feeding 0.5％adenine diet.The rats after modeling were randomly divided into model group,evodiamine low-and high-dose groups,Niaoduqing Granules group and evodiamine high-dose+K6PC-5(SphK1 activator)group.At the end of intervention,the levels of 24-hour urinary protein(24 h-UTP),serum urea nitrogen(BUN)and serum creatinine(SCr)were detected.The levels of monocyte chemoattractant protein 1(MCP-1)and interleukin 6(IL-6)in serum of rats were detected by enzyme-linked immunosorbent assay(ELISA).The pathological changes of renal tissue and collagen volume fraction(CVF)were observed by hematoxylin-eosin(HE)and Masson staining.The mRNA expressions of transforming growth factor β1(TGF-β1)and type Ⅳcollagen(COL-Ⅳ)in renal tissue were detected by real-time quantitative polymerase chain reaction(qRT-PCR).The protein expressions of SphK1 and S1P in renal tissue were detected by Western Blot.Results Compared with the normal group,the model group showed obvious inflammatory infiltration and collagen fiber deposition,the number of glomeruli decreased in renal tissue,and the expression levels of SCr,BUN,24h-UTP,IL-6,MCP-1,CVF,mRNA expressions of TGF-β1 and COL-Ⅳ,protein expessions of SphK1 and S1P were significantly increased(P＜0.05).Compared with the model group,the histopathological changes of the low-dose and high-dose evodiamine groups and the Niaoduqing Granules group was improved,and the expression levels of SCr,BUN,24 h-UTP,IL-6,MCP-1,CVF,mRNA expressions of TGF-β1 and COL-Ⅳ,protein expessions of SphK1 and S1P were significantly decreased.For intergroup comparison of each index,there were differences between the low-dose evodiamine group and the high-dose evodiamine group(P＜0.05),but there was no significant difference between the high-dose evodiamine group and the Niaoduqing Granules group(P＞0.05).Compared with the high-dose evodiamine group,the histopathological changes of the high-dose evodiamine+K6PC-5 group was further aggravated,and the improvement effect of all indexes were reversed(P＜0.05).Conclusion Evodiamine improves renal fibrosis in CRF rats by inhibiting SphK1/S1P signaling pathway.

Localized scleroderma (LoS) is a chronic autoimmune skin disorder characterized by fibrosis and hardening of the skin and subcutaneous tissues, potentially affecting deeper tissues and other organs. Currently, China lacks evidence-based guidelines for the diagnosis and management of LoS, which poses a challenge to disease recognition and leads to significant variation in treatment strategies across medical centers. To address this problem, we plan to establish a nationwide, multidisciplinary expert team through the Chinese Society of Plastic Surgery to initiate the development of the Chinese Guideline for the Diagnosis and Management of Localized Scleroderma. The guideline aims to standardize the diagnosis and treatment procedures for LoS, improve clinical diagnostic and therapeutic capabilities, and enhance patient outcomes through early identification and intervention. The guideline will adhere to international standards, with recommendations formed through evidence evaluation and multiple rounds of expert discussions. Although evidence-based data on LoS specific to the Chinese population is currently limited, and no unified gold standard for disease assessment exists, the clinical expertise of multidisciplinary specialists will play a pivotal role in the guideline's formulation. We anticipate that this guideline will provide LoS patients with higher-quality medical care and enhance patient awareness and engagement, which may ultimately help reduce social and healthcare burden. This proposal outlines the background, methodology, and anticipated value of the guideline, with the hope of providing guidance for its rigorous development and successful publication.

This work was aimed at predicting and verifying B-cell epitopes of SARS-CoV-2 E protein through bioinformatics methods,and clarifying the dominant B cell epitopes with mouse polyclonal antibody serum prepared through SARS-CoV-2 re-combinant E protein immunization and human positive serum vaccinated with inactivated SARS-CoV-2 vaccine.The structural and B-cell linear epitopes of SARS-CoV-2 E protein were predicted with SOPMA,Expasy,SWISS-MODEL,IEDB database,and Bepid-2.0 software.Candidate epitopes were expressed as GST-tagged recombinant protein fragments in an E.coli sys-tem,and their immunoreactivity with mouse and human poly-clonal positive serum against SARS-CoV-2 E protein was de-tected by western blotting and indirect ELISA,respectively.The epitope prediction results showed that E protein contained linear B cell epitopes Ser6-Val14 and Tyr57-Pro71,and the conformational epitopes of Glu8-Val12,Leu39-Tyr59,and Ser60-Leu65.The GST tagged recombinant E protein fragments of E1 and E3,containing Ser6-Val14 and Tyr57-Pro71 epitopes,respectively,as well as E2 without an epitope sequence as a control,were expressed in an E.coli expression system and successfully purified with an Ni-NTA column.Western blotting and indirect ELISA analysis indicated that all mouse and human SARS-CoV-2 positive sera positively reacted with only E1 and E3 proteins,but negatively reacted with E2 protein,thus indicating that the corresponding epitope prediction with Ser6-Val14 and Tyr57-Pro71 was correct.This study successfully predicted and preliminarily identified two linear B cell epitopes of SARS-CoV-2 E protein,thus providing a reference for the preparation of new coronavirus vaccines and the analysis of immune response characteristics.