Effects of metabolites of eicosapentaenoic acid on promoting transdifferentiation of pancreatic OL cells into pancreatic β cells / 中国药理学通报

Aim To investigate the role of metabolites of eicosapentaenoic acid (EPA) in promoting the transdifferentiation of pancreatic α cells to β cells. Methods Male C57BL/6J mice were injected intraperitoneally with 60 mg/kg streptozocin (STZ) for five consecutive days to establish a type 1 diabetes (T1DM) mouse model. After two weeks, they were randomly divided into model groups and 97% EPA diet intervention group, 75% fish oil (50% EPA +25% DHA) diet intervention group, and random blood glucose was detected every week; after the model expired, the regeneration of pancreatic β cells in mouse pancreas was observed by immunofluorescence staining. The islets of mice (obtained by crossing GCG

Effect of menthol on hypobaric hypoxia-induced pulmonary arterial hypertension in mice and its mechanism / 中国药理学通报

Aim To study the effect of menthol on hypobaric hypoxia-induced pulmonary arterial hypertension and explore the underlying mechanism in mice. Methods 10 to 12 weeks old wild type (WT) mice and TRPM8 gene knockout (TRPM8

Improved unilateral puncture PVP based on 3D printing technology for the treatment of osteoporotic vertebral compression fracture / 中国骨伤

OBJECTIVE@#To investigate the clinical effect of unilateral percutaneous vertebroplasty (PVP) combined with 3D printing technology for the treatment of thoracolumbar osteoporotic compression fracture.@*METHODS@#A total of 77 patients with thoracolumbar osteoporotic compression fractures from October 2020 to April 2022 were included in the study, all of which were vertebral body compression fractures caused by trauma. According to different treatment methods, they were divided into experimental group and control group. Thirty-two patients used 3D printing technology to improve unilateral transpedicle puncture vertebroplasty in the experimental group, there were 5 males and 27 females, aged from 63 to 91 years old with an average of (77.59±8.75) years old. Forty-five patients were treated with traditional bilateral pedicle puncture vertebroplasty, including 7 males and 38 females, aged from 60 to 88 years old with an average of(74.89±7.37) years old. Operation time, intraoperative C-arm X-ray times, anesthetic dosage, bone cement injection amount, bone cement diffusion good and good rate, complications, vertebral height, kyphotic angle (Cobb angle), visual analogue scale(VAS), Oswestry disability index (ODI) and other indicators were recorded before and after surgery, and statistically analyzed.@*RESULTS@#All patients were followed up for 6 to 23 months, with preoperative imaging studies, confirmed for thoracolumbar osteoporosis compression fractures, two groups of patients with postoperative complications, no special two groups of patients' age, gender, body mass index (BMI), time were injured, the injured vertebral distribution had no statistical difference(P>0.05), comparable data. Two groups of patients with bone cement injection, bone cement dispersion rate, preoperative and postoperative vertebral body height, protruding after spine angle(Cobb angle), VAS, ODI had no statistical difference(P>0.05). The operative time, intraoperative fluoroscopy times and anesthetic dosage were statistically different between the two groups(P<0.05). Compared with the traditional bilateral puncture group, the modified unilateral puncture group combined with 3D printing technology had shorter operation time, fewer intraoperative fluoroscopy times and less anesthetic dosage. The height of anterior vertebral edge, kyphosis angle (Cobb angle), VAS score and ODI of the affected vertebrae were statistically different between two groups at each time point after surgery(P<0.05).@*CONCLUSION@#In the treatment of thoracolumbar osteoporotic compression fractures, 3D printing technology is used to improve unilateral puncture PVP, which is convenient and simple, less trauma, short operation time, fewer fluoroscopy times, satisfactory distribution of bone cement, vertebral height recovery and kyphotic Angle correction, and good functional improvement.

Study on "Spectrum-material-effect" relationship of Compound Muji Granules against liver tumor based on microfluidic chip / 中国药理学通报

Aim To explore the material basis of anti-tumor effect of Compound Muji Granules. Methods The anti-tumor pharmacodynamics of Compound Muji Granules in vitro was studied by microfluidic chip technology. The fingerprint of Compound Muji Granules was established by HPLC. The "Spectrum-Material-Effect" of Compound Muji Granules was analyzed by grey correlation analysis,partial least squares regression analysis and network pharmacology approach. Results Seven batches of Compound Muji Granules with different extraction methods were successfully established. The results of grey correlation analysis showed that there was a positive correlation between Compound Muji Granules and 7 of the 14 components with pharmacodynamic correlation coefficient >0.80. The contribution of anti liver tumor was peak number 48(luteolin)>6(gallic acid)>19(chlorogenic acid)>59(quercetin)>67(kaempferol)>65(naringin)>38(ellagic acid),in that order. Conclusions Through the establishment of "Spectrum-Material-Effect" research method,it is clear that the above seven active monomers may be the anti-tumor material basis of Compound Muji Granules.

Effect of FKBP38 protein on endometrial precancerous lesions and mechanism / 中国药理学通报

Aim To build the model of the gene FKBP38(FK506 binding protein 38)conditional knock out in uterus and then investigate the effect on endometrial precancerous lesions and the underlying mechanism.Methods Transgenic mice whose FKBP38 gene was flanked with loxP were constructed by embryo microinjection. The conditional knockout of FKBP38 was obtained by breeding mice harboring two loxP sites in FKBP38(FKBP38

Structure-based design of novel heterocycle-substituted ATDP analogs as non-nucleoside reverse transcriptase inhibitors with improved selectivity and solubility

Following on our recently developed biphenyl-ATDP non-nucleoside reverse transcriptase inhibitor ZLM-66 (SI = 2019.80, S = 1.9 μg/mL), a series of novel heterocycle-substituted ATDP derivatives with significantly improved selectivity and solubility were identified by replacement of the biphenyl moiety of ZLM-66 with heterocyclic group with lower lipophilicity. Evidently, the representative analog 7w in this series exhibited dramatically enhanced selectivity and solubility (SI = 12,497.73, S = 4472 μg/mL) in comparison with ZLM-66 (SI = 2019.80, S = 1.9 μg/mL). This new NNRTI conferred low nanomolar inhibition of wild-type HIV-1 strain and tested mutant strains (K103N, L100I, Y181C, E138K, and K103N + Y181C). The analog also demonstrated favorable safety and pharmacokinetic profiles, as evidenced by its insensitivity to CYP and hERG, lack of mortality and pathological damage, and good oral bioavailability in rats (F = 27.1%). Further development of 7w for HIV therapy will be facilitated by this valuable information.

Primary assessment of the diversity of Omicron sublineages and the epidemiologic features of autumn/winter 2022 COVID-19 wave in Chinese mainland / 医学前沿

With the recent ongoing autumn/winter 2022 COVID-19 wave and the adjustment of public health control measures, there have been widespread SARS-CoV-2 infections in Chinese mainland. Here we have analyzed 369 viral genomes from recently diagnosed COVID-19 patients in Shanghai, identifying a large number of sublineages of the SARS-CoV-2 Omicron family. Phylogenetic analysis, coupled with contact history tracing, revealed simultaneous community transmission of two Omicron sublineages dominating the infections in some areas of China (BA.5.2 mainly in Guangzhou and Shanghai, and BF.7 mainly in Beijing) and two highly infectious sublineages recently imported from abroad (XBB and BQ.1). Publicly available data from August 31 to November 29, 2022 indicated an overall severe/critical case rate of 0.035% nationwide, while analysis of 5706 symptomatic patients treated at the Shanghai Public Health Center between September 1 and December 26, 2022 showed that 20 cases (0.35%) without comorbidities progressed into severe/critical conditions and 153 cases (2.68%) with COVID-19-exacerbated comorbidities progressed into severe/critical conditions. These observations shall alert healthcare providers to place more resources for the treatment of severe/critical cases. Furthermore, mathematical modeling predicts this autumn/winter wave might pass through major cities in China by the end of the year, whereas some middle and western provinces and rural areas would be hit by the upcoming infection wave in mid-to-late January 2023, and the duration and magnitude of upcoming outbreak could be dramatically enhanced by the extensive travels during the Spring Festival (January 21, 2023). Altogether, these preliminary data highlight the needs to allocate resources to early diagnosis and effective treatment of severe cases and the protection of vulnerable population, especially in the rural areas, to ensure the country's smooth exit from the ongoing pandemic and accelerate socio-economic recovery.

SENP2-mediated SERCA2a deSUMOylation increases calcium overload in cardiomyocytes to aggravate myocardial ischemia/reperfusion injury / 中华医学杂志(英文版)

BACKGROUND@#Sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) is a key protein that maintains myocardial Ca 2+ homeostasis. The present study aimed to investigate the mechanism underlying the SERCA2a-SUMOylation (small ubiquitin-like modifier) process after ischemia/reperfusion injury (I/RI) in vitro and in vivo .@*METHODS@#Calcium transient and systolic/diastolic function of cardiomyocytes isolated from Serca2a knockout (KO) and wild-type mice with I/RI were compared. SUMO-relevant protein expression and localization were detected by quantitative real-time PCR (RT-qPCR), Western blotting, and immunofluorescence in vitro and in vivo . Serca2a-SUMOylation, infarct size, and cardiac function of Senp1 or Senp2 overexpressed/suppressed adenovirus infected cardiomyocytes, were detected by immunoprecipitation, triphenyltetrazolium chloride (TTC)-Evans blue staining, and echocardiography respectively.@*RESULTS@#The results showed that the changes of Fura-2 fluorescence intensity and contraction amplitude of cardiomyocytes decreased in the I/RI groups and were further reduced in the Serca2a KO + I/RI groups. Senp1 and Senp2 messenger ribose nucleic acid (mRNA) and protein expression levels in vivo and in cardiomyocytes were highest at 6 h and declined at 12 h after I/RI. However, the highest levels in HL-1 cells were recorded at 12 h. Senp2 expression increased in the cytoplasm, unlike that of Senp1. Inhibition of Senp2 protein reversed the I/RI-induced Serca2a-SUMOylation decline, reduced the infarction area, and improved cardiac function, while inhibition of Senp1 protein could not restore the above indicators.@*CONCLUSION@#I/RI activated Senp1 and Senp2 protein expression, which promoted Serca2a-deSUMOylation, while inhibition of Senp2 expression reversed Serca2a-SUMOylation and improved cardiac function.

Difference of cervical and shoulder muscle performance and its correlation with pain and body mass index in patients with chronic neck pain / 中国康复理论与实践

ObjectiveTo test the inter-tester reliability and test-retest reliability of MyotonPRO for evaluating neck and shoulder muscle performance parameters in patients with unilateral chronic neck pain, observe the difference of muscle performance between the healthy and affected sides of patients with chronic neck pain, and analyze the factors that cause the imbalance of muscle performance in patients with chronic neck pain. MethodsFrom January to June, 2023, 32 patients with unilateral chronic neck pain in Guangdong Second Traditional Chinese Medicine Hospital were selected. Two testers used the same MyotonPRO equipment to measure the muscle tone, muscle hardness and muscle elasticity on both sides of the sternocleidomastoid muscle and the upper trapezius muscle in the relaxed position. Tester 1 repeated the measurement after an interval of 30 minutes, and Tester 2 was measured within the time interval between the two measurements of Tester 1. The intraclass correlation coefficient (ICC), standard error of mean (SEM) and minimum detectable change (MDC) were calculated simultaneously. The measurement results were plotted into Bland-Altman diagram and systematic bias analysis was performed. The difference in muscle characteristics between the affected side and the healthy side was compared. At the same time, the Visual Analogue Scale (VAS) score and body mass index (BMI) of the subjects were collected for correlation analysis. ResultsExcept the sternocleidomastoid muscle elasticity of the affected side (ICC = 0.697), the inter-tester reliability of all other parameters was high to very high (ICC = 0.719 to 0.952, SEM = 0.04 to 6.53, MDC = 0.12 to 18.11). The test-retest reliability of all parameters was high (ICC = 0.883 to 0.981, SEM = 0.03 to 5.72, MDC = 0.09 to 15.84). Bland-Altman plot analysis showed that the scatter distribution was consistent. The muscle tone, muscle hardness and muscle elasticity of sternocleidomastoid muscle and upper trapezius muscle were higher on the affected side than on the healthy side (t > 2.846, P < 0.05). The asymmetry index of tension, hardness and elasticity of upper trapezius muscle and sternocleidomastoid muscle was significantly positively correlated with VAS score and BMI (r > 0.385, P < 0.05). ConclusionMyotonPRO has good inter-tester reliability and retest reliability in evaluating the muscle performance of both sides of patients with chronic neck pain. The muscle tone, muscle hardness and muscle elasticity of sternocleidomastoid muscle and upper trapezius muscle on the affected side were higher than on the healthy side, and the difference of muscle performance was positively correlated with pain and BMI.

Equity analysis and policy suggestions for medical and health resource allocation in Inner Mongolia Autonomous Region / 上海预防医学

ObjectiveTo analyze the equity of medical and health resource allocation in 12 cities of Inner Mongolia Autonomous Region and to provide policy suggestions for further optimizing the allocation of medical and health resources. MethodsBased on two dimensions of geography and population， a comprehensive evaluation of the equity of medical and health resource allocation was conducted using location entropy， health resource density index （HRDI）， entropy-weighted TOPSIS method， and GIS spatial analysis. ResultsLocation entropy showed that the allocation of medical resources in each league city exceeded or approached 1 in the population dimension， but less than 1 in the geography dimension. HRDI revealed that the number of health institutions in Tongliao City was 8.3 times that of Alxa League； the number of beds， health technical personnel， practicing （assistant） physicians， and registered nurses in Wuhai City was 20.3 times， 18.2 times， 15.2 times， and 22.7 times that of Alxa League. The entropy-weighted TOPSIS method showed that the top three weighted indicators were registered nurses （24.14%）， health technical personnel （22.63%）， and practicing （assistant） physicians （21.13%）. Allocation of medical resources in Hulunbuir City， Xilinguole League， and Alashan League was significantly inequitable； GIS spatial analysis showed that the equity of medical resource allocation exhibited a decreasing distribution pattern from the central region to the western and eastern regions. ConclusionThere is a significant disparity in the equity of medical and health resource allocation among various leagues and cities， with resource allocation in the population dimension being better than in the geographical dimension. Allocation of medical and health human resources should be strengthened.

Research progress in biomimetic nano formulations of biofilms / 中国药科大学学报

@#Biomimetic nano formulations of biofilms have low immunogenicity, high targeting, and good biocompatibility, and can avoid being cleared by the endothelial reticular system, thus with in longer blood circulation time in the body.This article mainly reviews the main types as well as advantages and disadvantages of biomimetic nano formulations of biofilms, including tumor cell membranes, red blood cell membranes, platelet membranes, white blood cell membranes, stem cell membranes, extracellular vesicles (exosomes, microvesicles, and apoptotic bodies), endoplasmic reticulum membranes, and composite biofilms, with also a prospect of the challenges facing biomimetic nano formulations of biofilms and their future development based on their current research status, aiming to provide some insight for further research on biomimetic nano formulations of biofilms.

Expert knowledge-based strategies for ventilator parameter setting and stepless adaptive adjustment / 生物医学工程学杂志

The setting and adjustment of ventilator parameters need to rely on a large amount of clinical data and rich experience. This paper explored the problem of difficult decision-making of ventilator parameters due to the time-varying and sudden changes of clinical patient's state, and proposed an expert knowledge-based strategies for ventilator parameter setting and stepless adaptive adjustment based on fuzzy control rule and neural network. Based on the method and the real-time physiological state of clinical patients, we generated a mechanical ventilation decision-making solution set with continuity and smoothness, and automatically provided explicit parameter adjustment suggestions to medical personnel. This method can solve the problems of low control precision and poor dynamic quality of the ventilator's stepwise adjustment, handle multi-input control decision problems more rationally, and improve ventilation comfort for patients.

Treatment outcome of laparoscopic partial nephrectomy in patients with renal tumors of moderate to high complexity / 北京大学学报(医学版)

OBJECTIVE@#To investigate the treatment outcome of laparoscopic partial nephrectomy in the patients with renal tumors of moderate to high complexity (R.E.N.A.L. score 7-10).@*METHODS@#In the study, 186 patients with a renal score of 7-10 renal tumors who underwent laparoscopic partial nephrectomy in Peking University Third Hospital from February 2016 to April 2021 were selected. Laparoscopic partial nephrectomy was performed after examination. The patients were followed-up, and their postoperative hemoglobin, creatinine, complications, and length of hospital stay recorded. The data were represented by mean±standard deviation or median (range).@*RESULTS@#There were 128 males and 58 females in this group, aged (54.6±12.8) years, with body mass index of (25.4 ± 3.4) kg/m2; The tumors were located in 95 cases on the left and 91 cases on the right, with maximum diameter of (3.1±1.2) cm. The patient's preoperative hemoglobin was (142.9±15.8) g/L, and blood creatinine was 78 μmol/L (47-149 μmol/L). According to preoperative CT images, the R.E.N.A.L. score was 7 points for 43 cases, 8 points for 67 cases, 9 points for 53 cases, and 10 points for 23 cases. All the ope-rations were successfully completed, with 12 cases converted to open surgery. The operation time was 150 minutes (69-403 minutes), the warm ischemic time was 25 minutes (3-60 minutes), and the blood loss was 30 mL (5-1 500 mL). There were 9 cases of blood transfusions, with a transfusion volume of 800 mL (200-1 200 mL). Postoperative hemoglobin was (126.2±17.0) g/L. The preoperative crea-tinine was 78 μmol/L (47-149 μmol/L), the postoperative creatinine was 83.5 μmol/L (35-236 μmol/L), the hospital stay was 6 days (3-26 days), and surgical results achieved "the trifecta" in 87 cases (46.8%). In the study, 167 cases were followed up for 12 months (1-62 months), including 1 case with recurrence and metastasis, 4 cases with metastasis, and 2 cases with other tumors (1 case died).@*CONCLUSION@#Laparoscopic partial nephrectomy is safe and effective in the treatment of renal tumors with R.E.N.A.L. score of 7-10. Based on the complexity of the tumor, with the increase of difficulty, the warm ischemia time and operation time tend to increase gradually, while "the trifecta" rate gradually decreases. The complications of this operation are less, and the purpose of preserving renal function to the greatest extent is achieved.

Added value of shear-wave elastography in the prediction of extracapsular extension and seminal vesicle invasion before radical prostatectomy / 亚洲男科学杂志(英文版)

The purpose of this study was to analyze the value of transrectal shear-wave elastography (SWE) in combination with multivariable tools for predicting adverse pathological features before radical prostatectomy (RP). Preoperative clinicopathological variables, multiparametric magnetic resonance imaging (mp-MRI) manifestations, and the maximum elastic value of the prostate (Emax) on SWE were retrospectively collected. The accuracy of SWE for predicting adverse pathological features was evaluated based on postoperative pathology, and parameters with statistical significance were selected. The diagnostic performance of various models, including preoperative clinicopathological variables (model 1), preoperative clinicopathological variables + mp-MRI (model 2), and preoperative clinicopathological variables + mp-MRI + SWE (model 3), was evaluated with area under the receiver operator characteristic curve (AUC) analysis. Emax was significantly higher in prostate cancer with extracapsular extension (ECE) or seminal vesicle invasion (SVI) with both P < 0.001. The optimal cutoff Emax values for ECE and SVI were 60.45 kPa and 81.55 kPa, respectively. Inclusion of mp-MRI and SWE improved discrimination by clinical models for ECE (model 2 vs model 1, P = 0.031; model 3 vs model 1, P = 0.002; model 3 vs model 2, P = 0.018) and SVI (model 2 vs model 1, P = 0.147; model 3 vs model 1, P = 0.037; model 3 vs model 2, P = 0.134). SWE is valuable for identifying patients at high risk of adverse pathology.

Picomolar inhibitor of reverse transcriptase featuring significantly improved metabolic stability

Considering the undesirable metabolic stability of our recently identified NNRTI 5 (t1/2 = 96 min) in human liver microsomes, we directed our efforts to improve its metabolic stability by introducing a new favorable hydroxymethyl side chain to the C-5 position of pyrimidine. This strategy provided a series of novel methylol-biphenyl-diarylpyrimidines with excellent anti-HIV-1 activity. The best compound 9g was endowed with remarkably improved metabolic stability in human liver microsomes (t1/2 = 2754 min), which was about 29-fold longer than that of 5 (t1/2 = 96 min). This compound conferred picomolar inhibition of WT HIV-1 (EC50 = 0.9 nmol/L) and low nanomolar activity against five clinically drug-resistant mutant strains. It maintained particularly low cytotoxicity (CC50 = 264 μmol/L) and good selectivity (SI = 256,438). Molecular docking studies revealed that compound 9g exhibited a more stable conformation than 5 due to the newly constructed hydrogen bond of the hydroxymethyl group with E138. Also, compound 9g was characterized by good safety profiles. It displayed no apparent inhibition of CYP enzymes and hERG. The acute toxicity assay did not cause death and pathological damage in mice at a single dose of 2 g/kg. These findings paved the way for the discovery and development of new-generation anti-HIV-1 drugs.

Host protection against Omicron BA.2.2 sublineages by prior vaccination in spring 2022 COVID-19 outbreak in Shanghai / 医学前沿

The Omicron family of SARS-CoV-2 variants are currently driving the COVID-19 pandemic. Here we analyzed the clinical laboratory test results of 9911 Omicron BA.2.2 sublineages-infected symptomatic patients without earlier infection histories during a SARS-CoV-2 outbreak in Shanghai in spring 2022. Compared to an earlier patient cohort infected by SARS-CoV-2 prototype strains in 2020, BA.2.2 infection led to distinct fluctuations of pathophysiological markers in the peripheral blood. In particular, severe/critical cases of COVID-19 post BA.2.2 infection were associated with less pro-inflammatory macrophage activation and stronger interferon alpha response in the bronchoalveolar microenvironment. Importantly, the abnormal biomarkers were significantly subdued in individuals who had been immunized by 2 or 3 doses of SARS-CoV-2 prototype-inactivated vaccines, supporting the estimation of an overall 96.02% of protection rate against severe/critical disease in the 4854 cases in our BA.2.2 patient cohort with traceable vaccination records. Furthermore, even though age was a critical risk factor of the severity of COVID-19 post BA.2.2 infection, vaccination-elicited protection against severe/critical COVID-19 reached 90.15% in patients aged ≽ 60 years old. Together, our study delineates the pathophysiological features of Omicron BA.2.2 sublineages and demonstrates significant protection conferred by prior prototype-based inactivated vaccines.

Research progress in prevention and treatment of radiation-induced intestinal injury by traditional Chinese medicine active components / 中国中药杂志

Radiation-induced intestinal injury(RIII), a common complication of radiotherapy for pelvic malignancies, affects the quality of life and the radiotherapy efficacy for cancer. Currently, the main clinical approaches for the prevention and treatment of RIII include drug therapy, hyperbaric oxygen therapy, and surgical treatment. Among these methods, drug therapy is cost-effective. Traditional Chinese medicine(TCM) containing a variety of active components demonstrates mild side effects and good efficacy in preventing and treating RIII. Studies have proven that TCM active components, such as flavonoids, terpenoids, phenylpropanoids, and alkaloids, can protect the intestine against RIII by inhibiting oxidative stress, regulating the expression of inflammatory cytokines, modulating the mitochondrial apoptosis pathway, adjusting intestinal flora, and suppressing cell apoptosis. These mechanisms can help alleviate the symptoms of RIII. The paper aims to provide a theoretical reference for the discovery of new drugs for the prevention and treatment of RIII by reviewing the literature on TCM active components in the last 10 years.

Tra2β Enhances Cell Proliferation by Inducing the Expression of Transcription Factor SP1 in Cervical Cancer / 生物医学与环境科学（英文）

OBJECTIVE@#In this study, the role and potential mechanism of transformer 2β (Tra2β) in cervical cancer were explored.@*METHODS@#The transcriptional data of Tra2β in patients with cervical cancer from Gene Expression Profiling Interactive Analysis (GEPIA) and cBioPortal databases were investigated. The functions of Tra2β were evaluated by using Western blot, MTT, colony formation, Transwell assays, and nude mouse tumor formation experiments. Target genes regulated by Tra2β were studied by RNA-seq. Subsequently, representative genes were selected for RT-qPCR, confocal immunofluorescence, Western blot, and rescue experiments to verify their regulatory relationship.@*RESULTS@#The dysregulation of Tra2β in cervical cancer samples was observed. Tra2β overexpression in Siha and Hela cells enhanced cell viability and proliferation, whereas Tra2β knockdown showed the opposite effect. Alteration of Tra2β expression did not affect cell migration and invasion. Furthermore, tumor xenograft models verified that Tra2β promoted cervical cancer growth. Mechanically, Tra2β positively regulated the mRNA and protein level of SP1, which was critical for the proliferative capability of Tra2β.@*CONCLUSION@#This study demonstrated the important role of the Tra2β/SP1 axis in the progression of cervical cancer in vitro and in vivo, which provides a comprehensive understanding of the pathogenesis of cervical cancer.

Effects of chemical fertilizer reduction and organic fertilizer substitution on yield and quality of Saposhnikovia divaricata / 中国中药杂志

To explore the suitable fertilizing pattern for Saposhnikovia divaricata in the genuine producing area, a field trial was carried out to investigate the changes in the yield and quality of medicinal materials and soil in different fertilization patterns, such as organic fertilizer substitution(organic fertilizer+NPK fertilizer) and chemical fertilizer reduction(organic fertilizer+NPK fertilizer decrement and organic fertilizer+NPK fertilizer decrement+soil conditioner). The comprehensive analysis of all treatments was based on the medicine quality evaluation data set and soil quality evaluation data set, respectively, by CRITIC weight method. The results showed that(1) the yield of S. divaricate increased by 4.93%-12.67% under the organic fertilizer substitution mode, and the yield increased by 44.43% under the treatment of chemical fertilizer reduction YHT15, which was higher than that of the organic fertilizer substitution mode.(2) The quality of S. divaricate under the two fertilization modes was superior to the standard in the Chinese Pharmacopoeia, and the application of biochar was helpful to improve the quality of S. divaricate quality, with an increase of 82.83%-181.54%. CRITIC method analysis showed that fertilization treatments with high comprehensive scores were YHT15, YH30, and YH15.(3) Soil quality under the two fertilization modes was higher than that under the control. The fertilization treatments with higher comprehensive scores of soil quality were YHT15, YHT30, and YHT. The fertilization mode of adding biochar as soil conditioner, applying an appropriate amount of organic fertilizer, and reducing part of chemical fertilizer is the appropriate way to develop ecological plantation of S. divaricata in the Baicheng area in the western Jilin province. The specific fertilization mode is as follows. The basic fertilizer was 361 kg·hm~(-2) superphosphate+110 kg·hm~(-2) potassium sulfate+82 kg·hm~(-2) organic fertilizer+10 000 kg·hm~(-2) rice husk biochar, and urea was applied as top fertilizer three times, 29, 29, and 20 kg·hm~(-2), respectively.

Development of fluorine-substituted NH2-biphenyl-diarylpyrimidines as highly potent non-nucleoside reverse transcriptase inhibitors: Boosting the safety and metabolic stability

Our recent studies for nonnucleoside reverse transcriptase inhibitors identified a highly potent compound JK-4b against WT HIV-1 (EC50 = 1.0 nmol/L), but the poor metabolic stability in human liver microsomes (t 1/2 = 14.6 min) and insufficient selectivity (SI = 2059) with high cytotoxicity (CC50 = 2.08 μmol/L) remained major issues associated with JK-4b. The present efforts were devoted to the introduction of fluorine into the biphenyl ring of JK-4b, leading to the discovery of a novel series of fluorine-substituted NH2-biphenyl-diarylpyrimidines with noticeable inhibitory activity toward WT HIV-1 strain (EC50 = 1.8-349 nmol/L). The best compound 5t in this collection (EC50 = 1.8 nmol/L, CC50 = 117 μmol/L) was 32-fold in selectivity (SI = 66,443) compared to JK-4b and showed remarkable potency toward clinically multiple mutant strains, such as L100I, K103N, E138K, and Y181C. The metabolic stability of 5t was also significantly improved (t 1/2 = 74.52 min), approximately 5-fold higher than JK-4b in human liver microsomes (t 1/2 = 14.6 min). Also, 5t possessed good stability in both human and monkey plasma. No significant in vitro inhibition effect toward CYP enzyme and hERG was observed. The single-dose acute toxicity test did not induce mice death or obvious pathological damage. These findings pave the way for further development of 5t as a drug candidate.