Association of CYP7B1 expression with the prognosis of endometrial cancer: a retrospective study.

BACKGROUND: Endometrial cancer (EC) tissues express CYP7B1, but its association with prognosis needs to be investigated. METHODS: Immunohistochemistry and image analysis software were used to assess CYP7B1 protein expression in paraffin-embedded endometrial tumor sections. Associations between CYP7B1 and clinical factors were tested with the Wilcoxon rank-sum test. Kaplan-Meier curves were employed to describe survival, and differences were assessed using the log-rank test. Cox regression analysis was used to assess the association between CYP7B1 expression and the prognosis of patients with EC. RESULTS: A total of 307 patients were enrolled with an average age of 52.6 ± 8.0 years at diagnosis. During the period of follow-up, 46 patients (15.0%) died, and 29 (9.4%) suffered recurrence. The expression of CYP7B1 protein is significantly higher in the cytoplasm than in the nucleus (P < 0.001). Patients aged < 55 years (P = 0.040), ER-positive patients (P = 0.028) and PR-positive patients (P < 0.001) report higher levels of CYP7B1 protein. Both univariate (HR = 0.41, 95% CI: 0.18-0.90, P = 0.025) and multivariate (HR = 0.35, 95%CI:0.16-0.79, P = 0.011) Cox regression analyses demonstrate that high CYP7B1 protein expression predicts longer overall survival (OS). When considering only ER-positive patients (n = 265), CYP7B1 protein expression is more strongly associated with OS (HR = 0.20,95%CI:0.08-0.52, P = 0.001). The 3-year OS and 5-year OS in the low-CYP7B1 subgroup are 81.6% and 76.8%, respectively; while in the high-CYP7B1 subgroup are 93.0% and 92.0%, respectively (P = 0.021). CONCLUSIONS: High CYP7B1 protein expression predicted longer OS, suggesting that it may serve as an important molecular marker for EC prognosis.

Sophocarpine inhibits the progression of glioblastoma via PTEN/PI3K/Akt signaling pathway.

Glioblastoma multiforme (GBM) is the most fatal primary brain tumor which lacks effective treatment drugs. Alkaloids are known as a class of potential anti-tumor agents. Sophocarpine, a tetracyclic quinazoline alkaloid derived from Sophora alopecuroides L., possesses several pharmacological effects including anti-tumor effects in some malignancies. However, the effect and mechanism of sophocarpine on GBM remains to be explored. In this study, based on in vitro experiments, we found that sophocarpine significantly inhibited the viability, proliferation and migration of GBM cells including U251 and C6 cells in a dose- and time-dependent manner. Besides, sophocarpine arrested GBM cell cycle in G0/G1 phase and induced their apoptosis. Subsequently, we found that sophocarpine upregulated the expression of PTEN, a GBM tumor suppressor, and downregulated PI3K/Akt signaling in GBM cells. Moreover, inactivating of PTEN with bpV(phen) trihydrate partially restored the anti-GBM effects of sophocarpine via PI3K/Akt signaling. Finally, sophocarpine significantly inhibited the growth of tumor both in subcutaneous and orthotopic U251 xenograft GBM model in nude mice via PTEN/PI3K/Akt axis. Taken together, these results suggested that sophocarpine impeded GBM progression via PTEN/PI3K/Akt axis both in vitro and in vivo, providing with a promising therapy for treating GBM.

Immunoglobulin class-switch recombination: Mechanism, regulation, and related diseases.

Maturation of the secondary antibody repertoire requires class-switch recombination (CSR), which switches IgM to other immunoglobulins (Igs), and somatic hypermutation, which promotes the production of high-affinity antibodies. Following immune response or infection within the body, activation of T cell-dependent and T cell-independent antigens triggers the activation of activation-induced cytidine deaminase, initiating the CSR process. CSR has the capacity to modify the functional properties of antibodies, thereby contributing to the adaptive immune response in the organism. Ig CSR defects, characterized by an abnormal relative frequency of Ig isotypes, represent a rare form of primary immunodeficiency. Elucidating the molecular basis of Ig diversification is essential for a better understanding of diseases related to Ig CSR defects and could provide clues for clinical diagnosis and therapeutic approaches. Here, we review the most recent insights on the diversification of five Ig isotypes and choose several classic diseases, including hyper-IgM syndrome, Waldenström macroglobulinemia, hyper-IgD syndrome, selective IgA deficiency, hyper-IgE syndrome, multiple myeloma, and Burkitt lymphoma, to illustrate the mechanism of Ig CSR deficiency. The investigation into the underlying mechanism of Ig CSR holds significant potential for the advancement of increasingly precise diagnostic and therapeutic approaches.

Acute intermittent porphyria: a disease with low penetrance and high heterogeneity.

Acute intermittent porphyria (AIP) is caused by mutations in the gene encoding hydroxymethylbilane synthase (HMBS), a key enzyme in the heme biosynthesis pathway. AIP is an autosomal dominant disorder characterized by low penetrance and a highly heterogenous clinical presentation. The estimated prevalence of AIP is 5-10 cases per 100,000 persons, with acute attacks manifesting in less than 1% of the at-risk population. This low frequency of attacks suggests significant roles for oligogenic inheritance and environmental factors in the pathogenesis of the disease. In recent years, identification of several modifier genes has advanced our understanding of the factors influencing AIP penetrance and disease severity. This review summarizes these factors including the impact of specific HMBS mutations, oligogenic inheritance, mitochondrial DNA copy number, age, sex, the influence of sex hormones, and the role of environmental factors. Further studies into the etiology of AIP disease penetrance should inform pathogenesis, potentially allowing for the development of more precise diagnostic and therapeutic approaches.

Fabrication of a Near-Infrared-Emissive Probe for Detecting Dipeptidyl Peptidase 4 in the Liver of Diabetic Mice and Clinical Serum.

Dipeptidyl peptidase 4 (DPP4) plays a key role in glucose metabolism, which has been a close target for diabetes pathology and treatment. It is significant for the evaluation of cellular DPP4 activity in various biological systems. Fluorescence imaging technology is currently a popular method for detecting enzymes in living cells due to its advantages of high selectivity, high sensitivity, high spatiotemporal resolution, and real-time visualization. Herein, a near-infrared (NIR)-emissive probe NEDP with a large Stokes shift (153 nm) was developed for the assay of DPP4 activity. Upon addition of DPP4, NEDP can emit a significant turn-on NIR fluorescence signal (673 nm) with high sensitivity and specificity. Moreover, NEDP can successfully be used for imaging of intracellular DPP4, confirming the regulation of DPP4 expression in hyperglucose and its treatment in living cells. Most importantly, NEDP can not only monitor the changes of DPP4 in vivo but also show that DPP4 in diabetes is mainly up-regulated in the liver, and the level of DPP4 is positively correlated with the pathological damage of the liver. In addition, NEDP can identify the serum of diabetic patients from healthy people through the fluorescence response to DPP4. These results demonstrated that the designed probe NEDP provides a prospective visual tool to explore the relationship between DPP4 and diabetes and would be applied for detecting serum of diabetes in the clinic.

Construction of an Ohmic Contact Cathode by Two Metal Sulfides for efficient Capture and Catalysis of Polysulfide.

The slow reaction kinetics and severe shuttle effect of lithium polysulfide make Li-S battery electrochemical performance difficult to meet the demands of large electronic devices such as electric vehicles. Based on this, an electrocatalyst constructed by metal phase material (MoS2) and semiconductor phase material (SnS2) with ohmic contact is designed for inhibiting the dissolution of lithium polysulfide with improving the reaction kinetics. According to the density-functional theory calculations, it is found that the heterostructured samples with ohmic contacts can effectively reduce the reaction-free energy of lithium polysulfide to accelerate the sulfur redox reaction, in addition to the excellent electron conduction to reduce the overall activation energy. The metallic sulfide can add more sulfophilic sites to promote the capture of polysulfide. Thanks to the ohmic contact design, the carbon nanotube-MoS2-SnS2 achieved a specific capacity of 1437.2 mAh g-1 at 0.1 C current density and 805.5 mAh g-1 after 500 cycles at 1 C current density and is also tested as a pouch cell, which proves to be valuable for practical applications. This work provides a new idea for designing an advanced and efficient polysulfide catalyst based on ohmic contact.

PD-1 inhibitor plus concurrent chemoradiotherapy for high-risk locally advanced cervical cancer.

Aim: The prognosis of high-risk, locally advanced cervical cancer (LACC) remains poor following concurrent chemoradiotherapy (CCRT). We investigated whether the effect of CCRT can be enhanced by programmed cell death protein 1 (PD-1) inhibitor.Methods: A retrospective cohort study was conducted to compare the efficacy and safety of CCRT group (n = 82) and PD-1 inhibitor plus CCRT group (n = 70).Results: Compared with the CCRT group, the PD-1 inhibitor plus CCRT group had significantly higher objective response rate, median progression-free survival, leukopenia and fatigue. The addition of PD-1 inhibitor to CCRT showed a favorable trend in overall survival without statistical significance.Conclusion: PD-1 inhibitor plus CCRT presented a significant survival benefit and a manageable safety profile in high-risk LACC.

[Box: see text].

Deciphering tertiary lymphoid structure heterogeneity reveals prognostic signature and therapeutic potentials for colorectal cancer: a multicenter retrospective cohort study.

BACKGROUND: Tertiary lymphoid structures (TLSs) exert a crucial role in the tumor microenvironment (TME), impacting tumor development, immune escape, and drug resistance. Nonetheless, the heterogeneity of TLSs in colorectal cancer (CRC) and their impact on prognosis and treatment response remain unclear. METHODS: The authors collected genome, transcriptome, clinicopathological information, and digital pathology images from multiple sources. An unsupervised clustering algorithm was implemented to determine diverse TLS patterns in CRC based on the expression levels of 39 TLS signature genes (TSGs). Comprehensive explorations of heterogeneity encompassing mutation landscape, TME, biological characteristics, response to immunotherapy, and drug resistance were conducted using multiomics data. TLSscore was then developed to quantitatively assess TLS patterns of individuals for further clinical applicability. RESULTS: Three distinct TLS patterns were identified in CRC. Cluster 1 exhibited upregulation of proliferation-related pathways, high metabolic activity, and intermediate prognosis, while Cluster 2 displayed activation of stromal and carcinogenic pathways and a worse prognosis. Both Cluster 1 and Cluster 2 may potentially benefit from adjuvant chemotherapy. Cluster 3, characterized by the activation of immune regulation and activation pathways, demonstrated a favorable prognosis and enhanced responsiveness to immunotherapy. The authors subsequently employed a regularization algorithm to construct the TLSscore based on nine core genes. Patients with lower TLSscore trended to prolonged prognosis and a more prominent presence of TLSs, which may benefit from immunotherapy. Conversely, those with higher TLSscore exhibited increased benefits from adjuvant chemotherapy. CONCLUSIONS: The authors identified distinct TLS patterns in CRC and characterized their heterogeneity through multiomics analyses. The TLSscore held promise for guiding clinical decision-making and further advancing the field of personalized medicine in CRC.

Monomeric C-reactive protein is associated with severity and prognosis of decompensated hepatitis B cirrhosis.

C-reactive protein (CRP) is an acute-phase protein produced by the liver in response to infection and during chronic inflammatory disorders. Systemic inflammation is a major driver of cirrhosis progression from the compensated to the decompensated stage. Previous studies have shown that pentameric CRP (pCRP) to be a weak predictor of disease severity and prognosis in patients with decompensated hepatitis B cirrhosis, with it being only helpful for identifying patients with a higher short-term risk of death under certain conditions. Accumulating evidence indicates that pCRP dissociates to and acts primarily as the monomeric conformation (mCRP) at inflammatory loci, suggesting that mCRP may be a potentially superior disease marker with higher specificity and relevance to pathogenesis. However, it is unknown whether mCRP and anti-mCRP autoantibodies are associated with disease severity, or progression in decompensated hepatitis B cirrhosis. In this study, we evaluated the serum levels of mCRP and anti-mCRP autoantibodies in patients with decompensated cirrhosis of hepatitis B and their association with disease severity and theoretical prognosis. The results showed that patients with high mCRP and anti-mCRP autoantibody levels had more severe liver damage and that coagulation function was worse in patients with high anti-mCRP autoantibodies. Analysis of the correlation between pCRP, mCRP and anti-mCRP autoantibody levels with Model for End-Stage Liver Disease (MELD), Albumin-Bilirubin (ALBI), and Child-Turcotte-Pugh (CTP) prognostic scores showed that mCRP was the most strongly correlated with MELD score, followed by anti-mCRP autoantibodies; conversely, pCRP was not significantly correlated with prognostic score. Therefore, mCRP and anti-mCRP autoantibodies may be more advantageous clinical indicators than pCRP for evaluating the pathological state of decompensated hepatitis B cirrhosis.

Regulate the Solvation Structure and Interface by Nitrate in Phosphate-Based Electrolytes for 4.5 V-Class Ni-Rich Batteries.

Phosphate-based electrolyte propels the advanced battery system with high safety. Unfortunately, restricted by poor electrochemical stability, it is difficult to be compatible with advanced lithium metal anodes and Ni-rich cathodes. To alleviate these issues, the study has developed a phosphate-based localized high-concentration electrolyte with a nitrate-driven solvation structure, and the nitrate-derived N-rich inorganic interface shows excellent performance in stabilizing the LiNi0.8Co0.1Mn0.1O2 (NCM811) cathode interface and modulating the lithium deposition morphology on the anode. The results show that the Li|| NCM811 cell has exceptional long-cycle stability of >80% capacity retention after 800 cycles at 4.3 V, 1 C. A more prominent capacity retention rate of 93.3% after 200 cycles can be reached with the high voltage of 4.5 V. While being compatible with the phosphate-based electrolyte with good flame retardancy and the good electrochemical stability of Ni-rich lithium metal battery (LMBs) systems, the present work expands the construction of anion-rich solvation structures, which is expected to promote the development of the high-performance LMBs with safety.

Localized High-Concentration Sulfone Electrolytes with High-Voltage Stability and Flame Retardancy for Ni-Rich Lithium Metal Batteries.

The localized high-concentration electrolyte (LHCE) propels the advanced high-voltage battery system. Sulfone-based LHCE is a transformative direction compatible with high energy density and high safety. In this work, the application of lithium bis(trifluoromethanesulphonyl)imide and lithium bis(fluorosulfonyl)imide (LiFSI) in the LHCE system constructed from sulfolane and 1,1,2,2-tetrafluoroethyl-2,2,3,3-tetrafluoropropyl ether (TTE) is investigated. The addition of diluent causes an increase of contact ion pairs and ionic aggregates in the solvation cluster and an acceptable quantity of free solvent molecules. A small amount of LiFSI as an additive can synergistically decompose with TTE on the cathode and participate in the construction of both electrode interfaces. The designed electrolyte helps the Ni-rich system to cycle firmly at a high voltage of 4.5 V. Even with high mass load and lean electrolyte, it can keep a reversible specific capacity of 91.5% after 50 cycles. The constructed sulfone-based electrolyte system exhibits excellent thermal stability far beyond the commercial electrolytes. Further exploration of in-situ gelation has led to a quick conversion of the designed liquid electrolyte to the gel state, accompanied by preserved stability, which provides a direction for the synergistic development of LHCE with gel electrolytes.

Effect of mutation at c.493T>C locus of transcription factor HNF1α gene on its protein level.

Hepatocyte nuclear factor 1α (HNF1α) is a transcription factor that is crucial for the regulation to maintain the function of pancreatic ß-cell, hepatic lipid metabolism, and other processes. Mature-onset diabetes of the young type 3 is a monogenic form of diabetes caused by HNF1α mutations. Although several mutation sites have been reported, the specific mechanisms remain unclear, such hot-spot mutation as the P291fsinsC mutation and the P112L mutation and so on. In preliminary studies, we discovered one MODY3 patient carrying a mutation at the c.493T>C locus of the HNF1α gene. In this study, we analyzed the pathogenic of the mutation sites by using the Mutation Surveyor software and constructed the eukaryotic expression plasmids of the wild-type and mutant type of HNF1α to detect variations in the expression levels and stability of HNF1α protein by using Western blot. The analyses of the Mutation Surveyor software showed that the c.493T>C site mutation may be pathogenic gene and the results of Western blot showed that both the amount and stability of HNF1α protein expressed by the mutation type plasmid were reduced significantly compared to those by the wild type plasmid (P<0.05). This study suggests that the c.493T>C (p.Trp165Arg) mutation dramatically impacts HNF1α expression, which might be responsible for the development of the disease and offers fresh perspectives for the following in-depth exploration of MODY3's molecular pathogenic process.

[Effect of Low-Dose Recombinant Interleukin-2 Therapy on Immunocyte Subsets in Children with Solid Tumor].

OBJECTIVE: To evaluate the effect of low-dose recombinant interleukin-2 (rIL-2) therapy on immunocyte subsets and its side effects in children with solid tumor. METHODS: A total of 22 children (11 males and 11 females) with solid tumor in our department from December 2012 to November 2017 were selected, with a median age of 9 (3-16) years old when starting IL-2 therapy. ALL surgeries and chemotherapy of children had been completed before low-dose rIL-2 therapy, and 17 cases achieved complete remission (CR) and 5 cases achieved partial remission (PR). A low-dose rIL-2 therapy was given 1 month after chemotherapy for 1 year: 4×105 IU/(m2·d), s.c. for every other day, 3 times per week. The immunocyte subsets were detected every 3 months until the end of treatment, meanwhile, disease condition and therapy-related side effects were followed up. RESULTS: After low-dose rIL-2 therapy in 22 children, the absolute values of CD3+ T cells, CD3-CD56+ natural killer cells, CD3+CD4+ helper T cells (Th) and CD3+CD8+ cytotoxic T cells were up-regulated remarkably, as well as Th/suppressor T cells (all P < 0.05). While, there were no significant differences in absolute value and proportion of CD4+CD25+CD127- Treg cells during therapy. Among the 17 children who achieved CR before rIL-2 therapy, 14 cases continued to maintain CR after therapy, while 3 cases relapsed, and with 2 died after treatment abandonment. The 5 children who achieved PR before low-dose rIL-2 therapy were evaluated CR by PET/CT scan after treatment. In the early stage of low-dose rIL-2 therapy, 1 child developed skin rashes at the injection sites, and 2 children ran a slight to mild transient fever. Their symptoms disappeared without any organ damage after symptomatic treatment. CONCLUSION: Low-dose rIL-2 therapy has good drug tolerance, and changes the distribution of anti-tumor immune-cell subgroup in peripheral blood of children with solid tumor remarkably without up-regulation of absolute value and ratio of Treg cells.

Interface Engineering of MOF-Derived Co3O4@CNT and CoS2@CNT Anodes with Long Cycle Life and High-Rate Properties in Lithium/Sodium-Ion Batteries.

Metal-organic framework materials can be converted into carbon-based nanoporous materials by pyrolysis, which have a wide range of applications in energy storage. Here, we design special interface engineering to combine the carbon skeleton and nitrogen-doped carbon nanotubes (CNTs) with the transition metal compounds (TMCs) well, which mitigates the bulk effect of the TMCs and improves the conductivity of the electrodes. Zeolitic imidazolate framework-67 is used as a precursor to form a carbon skeleton and a large number of nitrogen-doped CNTs by pyrolysis followed by the in situ formation of Co3O4 and CoS2, and finally, Co3O4@CNTs and CoS2@CNTs are synthesized. The obtained anode electrodes exhibit a long cycle life and high-rate properties. In lithium-ion batteries (LIBs), Co3O4@CNTs have a high capacity of 581 mAh g-1 at a high current of 5 A g-1, and their reversible capacity is still 1037.6 mAh g-1 after 200 cycles at 1 A g-1. In sodium-ion batteries (SIBs), CoS2@CNTs have a capacity of 859.9 mAh g-1 at 0.1 A g-1 and can be retained at 801.2 mAh g-1 after 50 cycles. The unique interface engineering and excellent electrochemical properties make them ideal anode materials for high-rate, long-life LIBs and SIBs.

Influence of tillage methods combined with mulching on soil physical properties and potato yield in dry farming area under different precipitation years.

We conducted a field experiment in the dry farming area in south Ningxia from 2018 to 2021, to explore the influence of tillage methods combined with mulching on soil bulk density, aggregate content, soil water storage and potato yield under different precipitation years. There were four tillage methods (15 cm depth ploughing, and 30 cm, 40 cm and 50 cm depth subsoiling) and three mulching measures (mulching with oat straw, plastic film and no mulching), with the ploughing depth of 15 cm without mulching as control. The results showed the combination of tillage and mulching effectively reduced soil bulk density in 0-60 cm layer after three years of farming compared with that prior to the experiment. Under the same tillage mode, the best effect was achieved in mulching with oat straw under different precipitation years. To be specific, the best effect in 20 cm and 40 cm soil layers was achieved in mulching with oat straw for 30 cm depth subsoiling, in 60 cm soil layer for 15 cm ploughing in wet year, and for 40 cm depth subsoiling in 20 cm, 40 cm and 60 cm soil layers in normal and dry years. In 0-20 cm soil layer, the content of >0.25 mm soil aggregate was the highest for 40 cm depth subsoiling with oat straw mul-ching in all the three years. In 20-40 cm soil layer, the content was the highest for 15 cm depth ploughing with oat straw mulching in wet year, and for 40 cm depth subsoiling with oat straw mulching in normal and dry years. In 40-60 cm soil layer, content was the highest for 15 cm depth ploughing with plastic film mulching, 30 cm depth subsoiling with plastic film mulching, and 30 cm depth subsoiling with oat straw mulching in wet, normal and dry years, which was increased by 18.8%, 27.0%, and 35.8%, respectively, compared with the control. In the key growth stage (from squaring to tuber expansion) of potatoes, soil water storage in 0-100 cm layer was optimal for 30 cm depth subsoiling with oat straw mulching in wet year and for 40 cm depth subsoiling with oat straw mulching in normal and dry years, with an increase of 19.4%, 19.5%, and 23.7%, respectively. Potato yield was the highest for 30 cm depth subsoiling with oat straw mulching in wet year and for 40 cm depth subsoiling in normal and dry years, with an increase of 84.6%, 81.7%, and 106.3%, respectively. The correlation analysis showed that improved soil physical properties played a significant role in increasing potato yield, with the most significant role of soil bulk density and soil water storage at the squaring stage. Potato yield was high at a tillage depth of 34.67-36.03 cm. We concluded that the combination of tillage method and mulching could effectively improve soil physical pro-perties and increase soil water storage in the growth stage of potatoes, thereby significantly increa-sing potato yield. Potato yield in dry farming area could be enhanced through 30 cm depth subsoiling with oat straw mulching in wet years, and 40 cm depth subsoiling with oat straw mulching in normal and dry years.

Study on the preservation effects of the amputated forelimb by machine perfusion at physiological temperature.

PURPOSE: Ischemia and hypoxia are the main factors limiting limb replantation and transplantation. Static cold storage (SCS), a common preservation method for tissues and organs, can only prolong limb ischemia time to 4 - 6 h. The normothermic machine perfusion (NMP) is a promising method for the preservation of tissues and organs, which can extend the preservation time in vitro by providing continuous oxygen and nutrients. This study aimed to evaluate the difference in the efficacy of the 2 limb preservation methods. METHODS: The 6 forelimbs from beagle dogs were divided into 2 groups. In the SCS group (n = 3), the limbs were preserved in a sterile refrigerator at 4 °C for 24 h, and in the NMP group (n = 3), the perfusate prepared with autologous blood was used for the oxygenated machine perfusion at physiological temperature for 24 h, and the solution was changed every 6 h. The effects of limb storage were evaluated by weight gain, perfusate biochemical analysis, enzyme-linked immunosorbent assay, and histological analysis. All statistical analyses and graphs were performed using GraphPad Prism 9.0 one-way or two-way analysis of variance. The p value of less than 0.05 was considered to indicate statistical significance. RESULTS: In the NMP group, the weight gained percentage was 11.72% ± 4.06%; the hypoxia-inducible factor-1α contents showed no significant changes; the shape of muscle fibers was normal; the gap between muscle fibers slightly increased, showing the intercellular distance of (30.19 ± 2.83) µm; and the vascular α-smooth muscle actin (α-SMA) contents were lower than those in the normal blood vessels. The creatine kinase level in the perfusate of the NMP group increased from the beginning of perfusion, decreased after each perfusate change, and remained stable at the end of perfusion showing a peak level of 4097.6 U/L. The lactate dehydrogenase level of the NMP group increased near the end of perfusion and reached the peak level of 374.4 U/L. In the SCS group, the percentage of weight gain was 0.18% ± 0.10%, and the contents of hypoxia-inducible factor-1α increased gradually and reached the maximum level of (164.85 ± 20.75) pg/mL at the end of the experiment. The muscle fibers lost their normal shape and the gap between muscle fibers increased, showing an intercellular distance of (41.66 ± 5.38) µm. The contents of vascular α-SMA were much lower in the SCS group as compared to normal blood vessels. CONCLUSIONS: NMP caused lesser muscle damage and contained more vascular α-SMA as compared to SCS. This study demonstrated that NMP of the amputated limb with perfusate solution based on autologous blood could maintain the physiological activities of the limb for at least 24 h.

First Report of Erysiphe astragali Causing Powdery Mildew on Astragalus mongholicus in China.

Astragalus mongholicus Bge. [A. membranaceus Bge. var. mongholicus (Bge.) Hsiao] is a highly valuable perennial medicinal plant mainly distributed in China, whose dry roots are known as Huangqi in traditional Chinese medicine for reinforcing vital energy, strengthening superficial resistance, and promoting tissue regeneration (Lin et al. 2000). A. mongholicus roots of high quality are produced in Northwest and North China. Since July 2021, powdery mildew outbreaks happened annually on the leaves of A. mongholicus in a plantation (123° 56' 40'' E, 47° 22' 20'' N) in Qiqihar city, Heilongjiang Province, China. Disease incidence reached 100% by October (Fig. 1A-C), causing severe impairment of growth. Powdery mildew spots of circular or irregular shapes emerged on upper surface of leaf, resulting in plentiful lesion specks. Dense white hyphae appeared chaotically intertwined. Hyphae were hyaline and highly flexuous, 5.3 - 10.7 µm in diameter (n = 20). Chasmothecia were globose or slightly ovoid-shaped and turned dark brown when matured. Chasmothecia (diameter: 135.2 - 222.9 µm, n = 20) existed abundantly on the diseased leaves in the fields. Conidiophores were 89.0 - 129.9 µm in length (n = 20) and composed of one cylindrical, straight foot cell, followed by two cells and one to three conidia. Conidia were slim ellipsoid-shaped, occasionally ovoid-shaped, measuring 14.6 - 24.7 µm by 6.4 to10.4 µm, length/width ratio was 1.8 - 3.0 (n = 30). Hyphal appressoria were nipple-shaped and appeared in singular, occasionally in pairs. Unbranched germ tube emerged reaching out of the germinating conidia while forming an acute angle with the long axis. Comprehensively, the pathogen exhibited micro-morphology of the genus Erysiphe. For molecular identification, pathogen was carefully scraped off diseased leaves for DNA extraction. We used the DNA samples of three biological replicates for the sequencing of the ITS rDNA fragment (primers by (White et al. 1990). All the samples resulted in an identical ITS sequence (deposited in GenBank as OQ390098.1). It displayed 99.83% identity with OP806835.1 of an E. astragali voucher collected in Iran (Fig. 1D-M, O). Hence, our pathogen was identified as an E. astragali stain. Additionally, we amplified the Mcm7 sequence (using primers by (Ellingham et al. 2019), deposited as OQ397582.1). We propagated 40-day-old A. mongholicus plants via germinating seeds in pot soil and performed pathogenicity tests. Firstly, we incubated detached healthy leaves of propagated plants with severely symptomatic leaves collected from the fields in petri dishes under saturated moisture content and room temperature. Powdery mildew symptoms emerged on each healthy leaf (n = 5) after two weeks. Further, we infected healthy plants (n = 5) by gently pressing and rubbing symptomatic leaves on each healthy leaf, and kept them in a greenhouse (24 ℃, 80% humidity, 16/8-hour light/dark cycle). After a month, symptoms emerged on a number of leaves of each infected plant. We performed micromorphology observation (Fig. 1N-P) and ITS sequencing to confirm that the results fulfilled Koch's postulates. Powdery mildew caused by E. astragali on A. strictus in Tibet (Wang and Jiang 2023) and on A. scaberrimus in Inner Mongolia (Sun et al. 2023) have been reported. Here we report powdery mildew caused by E. astragali on Astragalus mongholicus for the first time. These Astragalus spp. are all acknowledged to have medicinal values in China but their usages are quite different.

Clinical feature and genetic analysis of HMBS gene in Chinese patients with acute intermittent porphyria: a systematic review.

Background: Early detection and diagnosis are important crucial to prevent life-threatening acute attacks in patients with acute intermittent porphyria (AIP). We aim to provide comprehensive data on the clinical and hydroxymethylbilane synthase (HMBS) gene variant characteristics and genotype-phenotype association of Chinese patients with AIP in order to improve clinicians' knowledge of AIP and reduce misdiagnosis and mistaken treatment. Methods: We searched the literature on Chinese patients with AIP in PubMed, Web of Science, Wiley Online Library, ScienceDirect and Chinese literature databases up to August 2023 in our analysis to explore the clinical and HMBS gene variant characteristics of Chinese patients with AIP. Results: A total of 41 original articles associated with Chinese AIP patients were included for analysis: 97 variants were detected in 160 unrelated families, including 35 missense, 29 frameshift, 24 splicing and 9 nonsense variants, with c.517C>T being the most common variant. Clinical data were reported in 77 of 160 patients: Most of them were female (67/77) and the age was 28.8 ± 9.9 years. The most common symptom was abdominal pain (73/77, 94.8%), followed by central nervous system symptoms (45/77, 58.4%). 13.0% (10/77) of patients experienced psychiatric symptoms. Hyponatremia was the most common electrolyte abnormality (42/77). 31 patients received carbohydrate loading therapy, and 30 of them were improved. 6 patients were treated with carbohydrate loading combined with hemin therapy and 5 eventually improved. All variants causing premature stop codons, frameshifts or enzyme activity center may experience more severe clinical phenotypes such as seizures, respiratory paralysis, intracranial hemorrhage disorder or respiratory failure. Conclusion: The most common presenting symptom in Chinese AIP patients was abdominal pain, followed by central nervous system symptoms. The HMBS gene analysis in Chinese AIP patients revealed that the heterogeneity is strong and the most common variant was missense mutation, with c.517C>T being the most common variant. The genotype-phenotype association helps guide clinical diagnosis and treatment. However, the treatment for AIP in China is limited and monolithic, and more attention needs to be paid to the treatment.

Functional insights of three RING-finger peroxins in the life cycle of the insect pathogenic fungus Beauveria bassiana.

Peroxisomes play important roles in fungal physiological processes. The RING-finger complex consists of peroxins Pex2, Pex10, and Pex12 and is essential for recycling of receptors responsible for peroxisomal targeting of matrix proteins. In this study, these three peroxins were functionally characterized in the entomopathogenic fungus Beauveria bassiana (Bb). These three peroxins are associated with peroxisomes, in which BbPex2 interacted with BbPex10 and BbPex12. Ablation of these peroxins did not completely block the peroxisome biogenesis, but abolish peroxisomal targeting of matrix proteins via both PTS1 and PTS2 pathways. Three disruptants displayed different phenotypic defects in growth on nutrients and under stress conditions, but have similar defects in acetyl-CoA biosynthesis, development, and virulence. Strikingly, BbPex10 played a less important role in fungal growth on tested nutrients than other two peroxins; whereas, BbPex2 performed a less important contribution to fungal growth under stresses. This investigation reinforces the peroxisomal roles in the lifecycle of entomopathogenic fungi and highlights the unequal functions of different peroxins in peroxisomal biology.