Quantum spin liquid signatures in monolayer 1T-NbSe2.

Quantum spin liquids (QSLs) are in a quantum disordered state that is highly entangled and has fractional excitations. As a highly sought-after state of matter, QSLs were predicted to host spinon excitations and to arise in frustrated spin systems with large quantum fluctuations. Here we report on the experimental observation and theoretical modeling of QSL signatures in monolayer 1T-NbSe2, which is a newly emerging two-dimensional material that exhibits both charge-density-wave (CDW) and correlated insulating behaviors. By using scanning tunneling microscopy and spectroscopy (STM/STS), we confirm the presence of spin fluctuations in monolayer 1T-NbSe2 by observing the Kondo resonance as monolayer 1T-NbSe2 interacts with metallic monolayer 1H-NbSe2. Subsequent STM/STS imaging of monolayer 1T-NbSe2 at the Hubbard band energy further reveals a long-wavelength charge modulation, in agreement with the spinon modulation expected for QSLs. By depositing manganese-phthalocyanine (MnPc) molecules with spin S = 3/2 onto monolayer 1T-NbSe2, new STS resonance peaks emerge at the Hubbard band edges of monolayer 1T-NbSe2. This observation is consistent with the spinon Kondo effect induced by a S = 3/2 magnetic impurity embedded in a QSL. Taken together, these experimental observations indicate that monolayer 1T-NbSe2 is a new promising QSL material.

Refractory lupus hepatitis successfully treated with telitacicept who failed to belimumab: A case report and literature review.

Background: Systemic lupus erythematosus (SLE)-associated hepatitis ("lupus hepatitis") was one of the most frequent causes of liver function abnormalities in patients with SLE. Lupus hepatitis (LH) is commonly treated with conventional treatment, including non-steroidal anti-inflammatory drugs, corticosteroids, and immunomodulators. However, in refractory cases, other treatment options may be required.Methodology: We report the case of a patient with lupus hepatitis refractory to both conventional therapy and belimumab who was successfully treated with telitacicept, a new dual B lymphocyte stimulator (BLyS)/APRIL (a proliferation-inducing ligand) inhibitor.Literature review was performed on PubMed search forum.Result: The specific search term was "telitacicept", 23 papers were searched, among them 10 case reports/series articles reporting telitacicept treatment were elected.Apart from our literature reporting the effectiveness of telitacicept in treating LH, there is no report on it in treating LH.Conclusion: This case suggests that telitacicept should be an effective and safe treatment for LH refractory, even to those who failed to belimumab based on the standard treatment, and can reduce the dosage of glucocorticoids.However, further investigations, particularly prospective randomized controlled trials, are warranted to verify our findings and ensure patient safety.

Seven lower toxicity celastrol derivatives by biotransformation of Pestalotiopsis sp. LGT-1.

Biotransformation of toxic components by plant endophytes has become an effective method to reduce the toxicity of target compounds and discover lead compounds. In this context, an endophytic fungus, Pestalotiopsis sp. LGT-1, from Tripterygium wilfordii Hook F. (TwHF), was used to reduce the toxicity of celastrol which is also produced by TwHF and is considered an attractive molecule with a variety of biological activities. Seven celastrol derivatives (1-7) were isolated from the coculture fermentation broth of LGT-1 and celastrol. Their structures were elucidated by spectroscopic data analysis including 1D and 2D NMR, as well as HRESIMS. Their absolute configurations were determined by analysis of NOESY, ECD data and NMR calculations. In cell proliferation experiments, the toxicity of seven compounds was 10.11- to 1.24-fold lower in normal cells than the prototype compound celastrol. These derivatives serve as potential candidates for future pharmaceutical applications.

Boosting Polyethylene Hydrogenolysis Performance of Ru-CeO2 Catalysts by Finely Regulating the Ru Sizes.

Hydrogenolysis is an effective method for converting polyolefins into high-value chemicals. For the supported catalysts commonly used, the size of active metals is of great importance. In this study, it is discovered that the activity of CeO2 -supported Ru single atom, nanocluster, and nanoparticle catalysts shows a volcanic trend in low-density polyethylene (LDPE) hydrogenolysis. Compared with CeO2 supported Ru single atoms and nanoparticles, CeO2 -supported Ru nanoclusters possess the highest conversion efficiency, as well as the best selectivity toward liquid alkanes. Through comprehensive investigations, the metal-support interactions (MSI) and hydrogen spillover effect are revealed as the two key factors in the reaction. On the one hand, the MSI is strongly related to the Ru surface states and the more electronegative Ru centers are beneficial to the activation of CH and CC bonds. On the other hand, the hydrogen spillover capability directly affects the affinity of catalysts and active H atoms, and increasing this affinity is advantageous to the hydrogenation of alkane species. Decreasing the Ru sizes can promote the MSI, but it can also reduce the hydrogen spillover effect. Therefore, only when the two effects achieve a balance, as is the case in CeO2 -supported Ru nanoclusters, can the hydrogenolysis activity be promoted to the optimal value.

Multiple Electronic Phases Coexisting under Inhomogeneous Strains in the Correlated Insulator.

Monolayer transition metal dichalcogenides (TMDs) can host exotic phenomena such as correlated insulating and charge-density-wave (CDW) phases. Such properties are strongly dependent on the precise atomic arrangements. Strain, as an effective tuning parameter in atomic arrangements, has been widely used for tailoring material's structures and related properties, yet to date, a convincing demonstration of strain-induced dedicate phase transition at nanometer scale in monolayer TMDs has been lacking. Here, a strain engineering technique is developed to controllably introduce out-of-plane atomic deformations in monolayer CDW material 1T-NbSe2 . The scanning tunneling microscopy and spectroscopy (STM and STS) measurements, accompanied by first-principles calculations, demonstrate that the CDW phase of 1T-NbSe2 can survive under both tensile and compressive strains even up to 5%. Moreover, significant strain-induced phase transitions are observed, i.e., tensile (compressive) strains can drive 1T-NbSe2 from an intrinsic-correlated insulator into a band insulator (metal). Furthermore, experimental evidence of the multiple electronic phase coexistence at the nanoscale is provided. The results shed new lights on the strain engineering of correlated insulator and useful for design and development of strain-related nanodevices.

Orbital distortion and electric field control of sliding ferroelectricity in a boron nitride bilayer.

Recent experiments confirm that two-dimensional boron nitride (BN) films possess room-temperature out-of-plane ferroelectricity when each BN layer is sliding with respect to each other. This ferroelectricity is attributed to the interlayered orbital hybridization or interlayer charge transfer in previous work. In this work, we attempt to understand the sliding ferroelectricity from the perspective of orbital distortion of long-pair electrons. Using the maximally localized Wannier function method and first-principles calculations, the out-of-planepzorbitals of BN are investigated. Our results indicate that the interlayer van der Waals interaction causes the distortion of the Npzorbitals. Based on the picture of out-of-plane orbital distortion, we propose a possible mechanism to tune the ferroelectric polarization by external fields, including electric field and stress field. It is found that both the polarization intensity and direction can be modulated under the electric field. The polarization intensity of the system can also be controlled by stress field perpendicular to the plane. This study will provide theoretical help in the device design based on sliding ferroelectrics.

Antimalarial activity and sensitization of chrysosplenetin against artemisinin-resistant genotype Plasmodium berghei K173 potentially via dual-mechanism of maintaining host P-glycoprotein homeostasis mediated by NF-κB p52 or PXR/CAR signaling pathways and regulating heme/haemozoin metabolism.

This study investigated antimalarial efficacy and sensitization of chrysosplenetin against artemisinin-resistant Plasmodium berghei K173 and potential molecular mechanism. Our data indicated a risk of artemisinin resistance because a higher parasitaemia% and lower inhibition% under artemisinin treatment against resistant parasites than those in the sensitive groups were observed. Two non-antimalarial components, verapamil and chrysosplentin, being P-gp inhibitors, possessed a strong efficacy against resistant parasites but it was not the case for Bcrp inhibitor novobiocin. Artemisinin-chrysosplenetin combination improved artemisinin susceptibility of resistant P. berghei. Artemisinin activated intestinal P-gp and Abcb1/Abcg2 expressions and suppressed Bcrp whereas chrysosplenetin reversed them. Resistant parasite infection led to a decreased haemozoin in organs or an increased heme in peripheral bloods compared with the sensitives; however, that in Abcb1-deficient knockout (KO)-resistant mice reversely got increased or decreased versus wild type (WT)-resistant animals. Chrysosplenetin as well as rifampin (nuclear receptor agonist) increased the transcription levels of PXR/CAR while showed a versatile regulation on hepatic and enternal PXR/CAR in WT- or KO-sensitive or -resistant parasites. Oppositely, hepatic and enteric NF-κB p52 mRNA decreased conformably in WT but increased in KO-resistant mice. NF-κB pathway potentially involved in the mechanism of chrysosplenetin on inhibiting P-gp expressions while PXR/CAR play a more complicated role in this mechanism.

Exploration and Practice of Medicine Pathway for Perioperative VTE Prophylactic Anticoagulant Treatment.

OBJECTIVE: Using perioperative VTE prophylactic anticoagulant pathway delicacy management, we aimed to explore the role of clinical pharmacists in perioperative VTE prophylactic anticoagulant treatment and the effect of the clinical medicine pathway implementation. METHODS: In compliance with evidence-based medicine, combined with clinical practice, clinical pharmacists participated in the formulation of the perioperative anticoagulant clinical medicine pathway. The PDCA cycle was strictly implemented. Urologic Department, Affiliated Hospital of Qingdao University, Qingdao Shandong, China, served as a pilot department for the evaluation of the effect of drug clinical pathway implementation. RESULTS: The anticoagulant clinical medicine pathway for the urologic department was formulated and implemented from October 2020 to August 2021. The entry rate gradually increased, and the accuracy of thrombosis risk assessment improved. The proportion of drugs in the department and the per capita drug cost decreased significantly. CONCLUSION: The perioperative VTE prophylactic anticoagulant pathway showed significant achievements in the rational use of urologic anticoagulant drugs, lowering the cost of medical care. Therefore, it could be considered a novel long-term mechanism for rational analgesia drug use.

Unveiling Electronic Behaviors in Heterochiral Charge-Density-Wave Twisted Stacking Materials with 1.25 nm Unit Dependence.

Layered charge-density-wave (CDW) materials have gained increasing interest due to their CDW stacking-dependent electronic properties for practical applications. Among the large family of CDW materials, those with star of David (SOD) patterns are very important due to the potentials for quantum spin liquid and related device applications. However, the spatial extension and the spin coupling information down to the nanoscale remain elusive. Here, we report the study of heterochiral CDW stackings in bilayer (BL) NbSe2 with high spatial resolution. We reveal that there exist well-defined heterochiral stackings, which have inhomogeneous electronic states among neighboring CDW units (star of David, SOD), significantly different from the homogeneous electronic states in the homochiral stackings. Intriguingly, the different electronic behaviors are spatially localized within each SOD with a unit size of 1.25 nm, and the gap sizes are determined by the different types of SOD stackings. Density functional theory (DFT) calculations match the experimental measurements well and reveal the SOD-stacking-dependent correlated electronic states and antiferromagnetic/ferromagnetic couplings. Our findings give a deep understanding of the spatial distribution of interlayer stacking and the delicate modulation of the spintronic states, which is very helpful for CDW-based nanoelectronic devices.

Dysfunctional microRNA-144-3p/ZBTB20/ERK/CREB1 signalling pathway is associated with MK-801-induced schizophrenia-like abnormalities.

Schizophrenia is a group of severe mental disorders. ZBTB20 is critical in brain development and corticogenesis and its dysfunction induces various neural disorders. ERK/CREB signalling is a potential downstream pathway of ZBTB20. Up-regulated microRNA-144-3p (miR-144-3p) were found in schizophrenic model rats in our previous study. This study investigated whether suppressed ZBTB20/ERK/CREB1 signalling caused by up-regulated miR-144-3p is associated with schizophrenia-like abnormalities in animals. A MK-801 rat model was established by 2-week MK-801 administration. An RNA-Seq test was performed to reveal differentially expressed genes in model rat hippocampus (HIP). MiR-144-3p-overexpressed SK-N-SH and 293T cell models were constructed by lentivirus, respectively. The in vitro and in vivo levels of miR-144-3p and ZBTB20, and the activation of the ERK/CREB1 signalling were examined by qRT-PCR, Western blots, or immunohistochemistry. The interaction between miR-144-3p and ZBTB20 was predicted and assessed by using bioinformatic methods and a luciferase reporter gene assay on 293T cells, respectively. The RNA-Seq test revealed that ZBTB20 was altered in the model rat HIP. Further experiments confirmed the reduced ZBTB20 mRNA and protein levels in the model rat HIP and caudate putamen (CPu), accompanied by increased miR-144-3p levels. Moreover, the ZBTB20 expression and ERK/CREB1 phosphorylation was decreased in the miR-144-3p-overexpressed 293T cells. These abnormal changes in the ZBTB20 expression and ERK/CREB1 phosphorylation levels were also observed in the model rat brain, but could be reversed by risperidone. In conclusion, this study revealed that dysfunctional miR-144-3p/ZBTB20/ERK/CREB1 signalling might be associated with schizophrenia-like abnormalities, suggesting potential therapeutic targets for future schizophrenia treatment.

Inflammation-related Gene Polymorphisms Associated With Childhood Acute Lymphoblastic Leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is a malignant hematological disease and is often accompanied by a variety of genetic abnormalities. The pathogenesis of inflammation-related single-nucleotide polymorphism (SNP) in children with ALL remains unclear. OBJECTIVE: This study was to discover the association of the SNP sites of some inflammation-related genes and the susceptibility and treatment response of ALL in children, so as to provide personalized treatment for ALL in children. PROCEDURE: One hundred sixty-five childhood ALL patients and 175 age-matched healthy participants were recruited in this study. We investigated the involvement of 31 SNPs of the inflammation-related genes in the pathogenesis and treatment response of childhood ALL. RESULTS: Statistical analysis revealed that rs2280714 in IRF5, rs2297630 in SDF-1, rs4353135 in NLRP3, rs1946518 in interleukin-18 were related to the susceptibility to pediatric ALL. Interleukin-1ß rs16944 SNP was correlated with ALL risk stage in children. Rs7633631 in CD226 and rs10818488 in TRAF1 were related to the minimal residual disease (MRD) on day 15 and day 33. CONCLUSIONS: Certain SNPs of inflammation genes were associated with the susceptibility and treatment response of ALL children. These findings may help in the early detection, diagnostic evaluation, and making individual chemotherapy regimen for ALL children according to the genotype of these sites at the time of initial diagnosis.

Detection of cytomegalovirus (CMV) by digital PCR in stool samples for the non-invasive diagnosis of CMV gastroenteritis.

BACKGROUND: CMV gastroenteritis is common in patients receiving allogeneic hematopoietic stem cell transplantation and it is difficult to distinguish from acute graft-versus-host disease (aGvHD), which has very similar symptoms but needs quite different treatment. CMV gastroenteritis is caused by local infection or reactivation of CMV in the gastrointestinal tract while aGvHD is due to immune rejection. The gold standard of diagnosis of CMV gastroenteritis and aGvHD is gastrointestinal biopsy under endoscopy, which is invasive and can potentially lead to severe side effects. Stool samples testing with quantitative polymerase chain reaction (qPCR) may be an alternative, while the application in trace level measurements and precision are not all satisfactory enough in reported research. METHODS: In this study, we designed a novel method that extracted the cell free DNA (cfDNA) from the fecal supernatant to perform digital PCR (dPCR) for the detection of CMV, analyzed the performance and compared it with the total DNA extracted by the current procedure. RESULTS: Twenty-two paired stool samples using two DNA extraction methods proved that the cfDNA extraction method had markedly higher DNA concentrations and control gene copy number, suggesting that cfDNA may be more informative and more useful for the detection of CMV DNA segment. The dPCR approach in detecting CMV DNA segment also exhibit good linearity (R2 = 0.997) and higher sensitivity (limit of detection at 50% was 3.534 copies/µL). Eighty-two stool samples from 44 immunocompromised patients were analyzed, CMV-positive rate was 28%, indicating that more than one-quarter of the gastrointestinal symptoms within these patients may be caused by CMV infection or reactivation. CONCLUSION: The combined results suggest that detection of CMV by dPCR in cfDNA of stool supernatant is a powerful method to identify CMV gastroenteritis and helps in clinical treatment decision making.

Effects of icariin on alleviating schizophrenia-like symptoms by regulating the miR-144-3p/ATP1B2/mTOR signalling pathway.

Schizophrenia is a group of severe mental disorders. Icariin is a main active component of Epimedium, possessing therapeutic effects on various neurodegenerative diseases. The present study investigated whether icariin is effective in alleviating schizophrenia-like symptoms and explored its underlying molecular mechanism. A developmental schizophrenia rat model employing 2-week repeated MK-801 administration was established. Icariin was orally administrated 3 time per day for 2 weeks after the MK-801 administration. Open-field test (OFT), novel object recognition (NOR), rotarod, and Morris water maze (MWM) were performed to examine the therapeutic effects of icariin on behavioural abnormalities. Hematoxylin-eosin (HE) staining on hippocampus slices, and MTT assay and Calcein/PI staining on the SK-N-SH cells treated with MK-801 were carried out to assess the neuroprotective effects of icariin. Furthermore, the regulation of icariin on the miR-144-3p/ATP1B2/mTOR signalling pathway was examined by RT-PCR and Western blots. The results showed that icariin alleviated MK-801-induced anxiety and recognition memory deficits in the OFT and NOR, respectively. Additionally, weakened motor coordination caused by MK-801 was restored by icariin. The MWM test also showed that icariin can improve MK-801-induced impaired spatial memory and swimming ability. Furthermore, brain grey matter atrophy, cytotoxicity, and cell apoptosis caused by MK-801 can be eliminated by icariin. Lastly, icariin can regulate the expression of miR-144-3p and ATP1B2, and enhance the phosphorylation of PI3K, Akt, and mTOR. In conclusion, this study revealed that icariin may have therapeutic effects on schizophrenia-like disorders via regulating the miR-144-3p/ATP1B2/mTOR signalling, suggesting that icariin has potential to become an antipsychotic drug.

Clinical characteristics and prognosis of 16 relapsed/refractory B-cell malignancy patients with CAR T-cell-related hyperferritinaemia.

With the success of chimeric antigen receptor-modified (CAR) T-cell therapy for relapsed/refractory (r/r) B-cell malignancies, severe complications after CAR T-cell infusion have emerged as nonnegligible prognosis-related factors. However, the prognosis of patients with CAR T-cell-related hyperferritinaemia (HFA) is unclear. We report the efficacy and safety of CAR T-cell therapy in 16 r/r B-cell malignancy patients with CAR T-cell-related HFA. The rates of serum ferritin levels above 10,000 ng/ml during CAR T-cell therapy were 6.2% and 14.3% in B-cell non-Hodgkin's lymphoma (B-NHL) and acute B lymphocyte leukemia (B-ALL), respectively. These patients were characterized by an extremely high tumor burden and a high rate of extranodal involvement. In lymphoma, the complete remission (CR) rate was 37.5% (3/8), which was lower than that in the control group with the lowest value of ferritin (CR was 87.5% (7/8), P=0.0406), and it could also be seen that the OS of the control group (1-year OS rate 100%) had a better trend than HFA group (1-year OS rate 50%). In the B-ALL patients, the OS of the control group (1-year OS rate 100%) was higher than HFA group (1-year OS rate 45%, P=0.0189), although there was no significant difference in CR rate. High-grade CRS (≥3) occurred in 56.25% of the patients, and the mortality rate was 56.25%, which was significantly higher than control group (12.5% and 12.5%, P=0.009). The peak serum ferritin level in the patients who died of CRS was significantly higher than others (P=0.0168). Regardless of whether the CAR T-related MAS diagnostic criteria were met, there was no significant difference in ORR and OS in HFA group, however patients with MAS showed a higher rate of high-grade CRS. Interestingly, in our study, glucocorticoid intervention in HFA group showed little impact on expansion of CAR-T cells, whether compared with control group or compared within HFA group by dividing patients into high and low dosage subgroups based on the median dose of glucocorticoid. High mortality was observed in patients with CAR T-cell-related HFA. Early glucocorticoid intervention might be worth trying to improve the safety of CAR T therapy in these patients.

Comparison of Droplet Digital PCR and Metagenomic Next-Generation Sequencing Methods for the Detection of Human Herpesvirus 6B Infection Using Cell-Free DNA from Patients Receiving CAR-T and Hematopoietic Stem Cell Transplantation.

Purpose: The aim of this study was to examine and compare the differences between droplet digital PCR (ddPCR) and metagenomic next-generation sequencing (mNGS) in the detection of human herpesvirus 6B (HHV-6B). Long-term monitoring of HHV-6B viral load in patients receiving chimeric antigen receptor-modified T-cell (CAR-T) therapy and hematopoietic stem cell transplantation (HSCT) can be used to identify immune effector cell-associated neurotoxicity syndrome (ICANS) and guide drug therapy. Methods: Twenty-seven patients with suspected HHV-6B infection who had both mNGS and ddPCR test results were analyzed retrospectively, including 19 patients who received CAR T-cell therapy and 8 who received HSCT. The HHV-6B probe and primers were designed, and the performance of the ddPCR assay was evaluated. Subsequently, ddPCR was performed utilizing blood and urine. Data on clinical information and mNGS investigations were collected. Results: The ddPCR test results correlated significantly with the mNGS test results (P < 0.001, R2 = 0.672). Of the 27 time-paired samples, ddPCR showed positive HHV-6B detection in 20 samples, while mNGS alone showed positive HHV-6B detection in 12 samples. ddPCR detected additional HHV-6B infections in 8 samples that would have been missed if only mNGS were used. In addition, the first HHV-6B infection event was detected at a median of 14 days after CAR T-cell infusion (range, 8 to 19 days). Longitudinal monitoring of HHV-6B by ddPCR was performed to assess the effectiveness of antiviral therapy. The data showed that with antiviral treatment HHV-6B viral load gradually decreased. Conclusion: Our results indicated that ddPCR improved the HHV-6B positive detection ratio and was an effective adjunct to mNGS methods. Furthermore, the longitudinal detection and quantification of HHV-6B viral load in patients undergoing CAR T-cell therapy and HSCT may serve as a guide for drug treatment.

Pathogen Distribution and Antimicrobial Resistance of Early Onset Sepsis in Very Premature Infants: A Real-World Study.

INTRODUCTION: Early onset sepsis (EOS) remains a potentially fatal newborn condition, especially in very preterm infants. Data on the pathogen distribution and antibiotic susceptibility patterns of EOS among very preterm infants are scarce but essential for the choice of empirical antibiotic administration. We sought to assess the epidemiologic characteristics and antibiotic susceptibility patterns of pathogens causing EOS among a cohort of very preterm infants in China. METHODS: This prospective, observational study included a cohort of infants born at a gestational age (GA) less than 32 weeks of 32 newborn intensive care units (NICUs) in China between January 1, 2018 and December 31, 2020. EOS was defined by isolation of pathogenic species from blood culture within 72 h of birth. RESULTS: A total of 108 EOS cases (18.4 per 1000 admissions) were identified among 5865 very preterm infants. Incidence of EOS increased with the decrease of GA and birthweight. Escherichia coli (n = 44, 40.7%) was the most common pathogen, followed by Klebsiella spp. (n = 10, 9.3%). The distribution and proportion of pathogenic bacteria varied significantly by GA. E. coli and Klebsiella spp. showed high resistance to ampicillin and third-generation cephalosporins, while they showed good susceptibility to carbapenem antibiotics and piperacillin-tazobactam. CONCLUSION: Our data demonstrated that pathogens causing neonatal EOS showed high rates of resistance to ampicillin and third-generation cephalosporins. This raised questions about the best empirical antibiotic choice for preterm infants suspected of having EOS in low- and middle-income countries (LMICs).

Effects of Solution Temperature on Tensile Properties of a High γ' Volume Fraction P/M Superalloy.

To meet the pressing needs concerning the optimization of the performance of powder metallurgy (P/M) superalloys for turbine disc applications, the effects of solution temperature on a novel high γ' volume fraction P/M superalloy FGH 4107 were investigated. The results indicated that the size of the γ' precipitates decreased dramatically as the solution temperature increased from 1160 to 1200 °C. Theoretical calculations showed that the precipitation strengthening played a dominant role in enhancing the strength of the high γ' volume fraction P/M superalloy, and a higher solution temperature was beneficial for the modification of the γ' phase distribution during the following cooling and aging process.

Risk Factors and Incidence of Malignancy After Kidney Transplant in Mainland China: A Single-Center Analysis.

OBJECTIVES: Malignancy is a common cause of death in renal transplant patients. The aim of this study was to investigate incidence, risk factors, and survival rates associated with posttransplant malignancy in kidney transplant recipients. MATERIALS AND METHODS: Between January 2015 and December 2020, 1154 patients underwent kidney transplant at the Affiliated Hospital of Qingdao University. Patients with a history of malignancy or other organ transplant(liver, pancreas, heart, orlungs) were excluded from this study. Patients with incomplete follow-up records were also excluded. Ultimately, our study comprised 811 kidney transplant recipients. The patient characteristics and incidence, type, and risk factors associated with posttransplant malignancy were examined. We also analyzed the overall survival of recipients with posttransplant malignancy. RESULTS: A total of 811 renal transplant recipients were followed up, with a median follow-up period of 3.0 years. Fourteen kidney recipients developed posttransplant malignancy (1.7%), with a mean time to malignancy diagnosis of 2.7 years. The 3-year and 5-year overall survival rates were 91.7% and 91.7%, respectively, in recipients with malignancy and 99.2% and 98.8%, respectively, in recipients without malignancy. The overall survival rate was significantly higher in recipients without malignancy than in those with malignancy (P = .03). Female sex, older recipient age, and history of prior kidney transplant were significant predictors of malignancy development. CONCLUSIONS: Postoperative malignancy in kidney transplantrecipients was associated with lower overall survival rates. Malignancy screening is important for kidney transplant patients, especially for older women and patients with a history of prior kidney transplant.

Native Endophytes of Tripterygium wilfordii-Mediated Biotransformation Reduces Toxicity of Celastrol.

Celastrol (1), obtained from the roots of Tripterygium wilfordii Hook F., is most likely to become an antitumor drug, but with severe cytotoxicity. Due to the lack of modifiable sites in the structure of celastrol, the structural diversity of the modified products obtained by synthesis in the previous studies is insufficient, which hinders the pace of its patent medicine. This study describes a method of microbial transformation to increase the modification site of celastrol and reduce its toxicity. The screening of endophytes from native plants was introduced in this context, which led to two novel stereoselective oxidation products such as S-16-hydroxyl celastrol (2) and A-ring aromatized S-16-hydroxyl celastrol (3), along with a rare 7,9-octadecadienoic acid ester of celastrol (4). Their structures were determined by extensive spectroscopic data analysis, especially 1D and 2D NMR. Compared with 1, compounds 3 and 4 exhibited similar antitumor activity in U251, A549, KG-1, and B16 cell lines. Compound 2 had slightly decreased antitumor activity when compared with compound 1. Furthermore, compound 2-4 showed lower cytotoxicity against BV-2 (about 21-fold lower, 2: 92.82 µM, 3: 34.25 µM, and 4: 74.75 µM vs. celastrol: 4.35 µM), and also identical trends against H9c2 and PC12 cell lines.

Medications on hypertension, hyperlipidemia, diabetes, and risk of amyotrophic lateral sclerosis: a systematic review and meta-analysis.

OBJECTIVE: To investigate the association between the use of common medications on hypertension, hyperlipidemia, diabetes, and the risk of amyotrophic lateral sclerosis (ALS). METHODS: PubMed, EMBASE, OVID, and Web of Science were searched systematically until December 2021 for studies quantitatively investigating the effect of medications on hypertension, hyperlipidemia, and diabetes on the risk of ALS. We conducted a fixed-effects model or random-effects meta-analysis to calculate the summary ORs (odds ratios) and 95%CIs (confidence intervals). RESULTS: Regular intake of angiotensin-converting enzyme inhibitors (ACEIs) (OR: 0.81, 95%CI: 0.74, 0.89), beta-blockers (OR: 0.82, 95%CI: 0.76, 0.90), calcium-channel blockers (CCBs) (OR: 0.85, 95%CI: 0.79, 0.93), or diuretics (OR: 0.87, 95%CI: 0.81, 0.93) was inversely associated with the incidence of ALS. There was no significant association between statin use and risk of ALS (OR: 0.92, 95%CI: 0.83, 1.03). Metformin (OR: 0.83, 95%CI: 0.75, 0.93) and sulfonylureas (OR: 0.79, 95%CI:0.71, 0.89) use could significantly reduce the risk of ALS. CONCLUSION: Regular use of anti-hypertensive drugs and anti-diabetes including ACEIs, beta-blockers, CCBs, diuretics, metformin, and sulfonylureas could protect against the incidence of ALS. No significant association between anti-hyperlipidemia drug use and risk of ALS was revealed. Regular medications for hypertension, hyperlipidemia, and diabetes should be recommended regardless of the diagnosis of ALS.