Sublethal effect and detoxifying metabolism of metaflumizone and indoxacarb on the fall armyworm, Spodoptera frugiperda.

The fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith) (Lepidoptera, Noctuidae), is a highly polyphagous invasive pest that damages various crops. Pesticide control is the most common and effective strategy to control FAW. In this study, we evaluated the toxicity of metaflumizone and indoxacarb against third-instar FAW larvae using the insecticide-incorporated artificial diet method under laboratory conditions. Both metaflumizone and indoxacarb exhibited substantial toxicity against FAW, with LC50 values of 2.43 and 14.66 mg/L at 72 h, respectively. The sublethal effects of metaflumizone and indoxacarb on parental and F1 generation FAW were investigated by exposing third-instar larvae to LC10 and LC30 concentrations of these insecticides. Sublethal exposure to these two insecticides significantly shortened adult longevity, extended pupal developmental times and led to reduced pupal weight, pupation rates, and adult fecundity in the treated parental generation and F1 generation at LC10 or LC30 concentrations, in comparison to the control group. The larval developmental times were shortened in the parental generation but prolonged in the F1 generation, after being treated with sublethal concentrations of metaflumizone. Furthermore, larvae exposed to LC10 or LC30 concentrations of indoxacarb exhibited elevated activity levels of cytochrome P450 monooxygenase and glutathione S-transferase, which coincides with the observed synergistic effect of piperonyl butoxide and diethyl maleate. In conclusion, the high toxicity and negative impact of metaflumizone and indoxacarb on FAW provided significant implications for the rational utilization of insecticides against this pest.

Clinical and genetic characterization of a Chinese family with pontocerebellar hypoplasia type 7.

We report compound heterozygous variants in TOE1 in siblings of Chinese origin who presented with dyskinesia and intellectual disabilities. Our report provides further information regarding the etiology and pathogenesis of pontocerebellar hypoplasia type 7 syndrome (PCH7). Clinical manifestations were obtained, and genomic DNA was collected from family members. Whole-exome and Sanger sequencing were performed to identify associated genetic variants. Bioinformatics analysis was conducted to identify and characterize the pathogenicity of the heterozygous variants. Following long-term rehabilitation, both siblings showed minimal improvement, and their condition tended to progress. Whole-exome sequencing revealed two unreported heterozygous variants, NM_025077: c.C553T (p.R185W) and NM_025077: c.G562T (p.V188L), in the TOE1 gene mapped to 1p34.1. Sanger sequencing confirmed that the two variants in the proband and her brother were inherited from their parents. The NM_025077: c.C553T (p.R185W) variant was inherited from the father, and the NM_025077: c.G562T (p.V188L) variant was inherited from the mother. Although the two variants in the TOE1 gene have not been reported previously, they were associated with PCH7 based on integrated analysis. Thus, our report contributes to our knowledge regarding the etiology and phenotype of PCH 7.

Clinicopathological features and molecular genetic changes in 17 cases of uterine tumor resembling ovarian sex cord tumor.

Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare mesenchymal neoplasm that was recently reported to exhibit recurrent NCOA1-3rearrangement with the most frequent partners ESR1 and GREB1. In this study, the clinicopathological characteristics of 17 UTROSCT cases were summarized; among them, the fusion genes of 12 cases were retrospectively analyzed by targeted RNA sequencing. The mean age of our cohort was 47 years (19-67 y). Although the majority of UTROSCTs had clear boundaries on gross examination, microscopic infiltration into the myometrium was observed in 82.4 % of cases. The tumor cells showed diffuse, trabecular, nested, reticular, pseudopapillary, hollow and solid tubular patterns, expressing sex cord, epithelial, and myogenic markers. Six fusion genes, including ESR1::NCOA3 (n = 4), ESR1::NCOA2 (n = 2), ESR1::CITED2 (n = 2), GREB1::NCOA2 (n = 2), GREB1::NCOA1 (n = 1), and GREB1::NCOA3 (n = 1), were identified. The fusion genes of the three cases with recurrence and metastasis were GREB1::NCOA2, ESR1::NCOA3, and ESR1::CITED2. All 3 cases of recurrent tumors showed infiltrative growth, with moderate to severe dysplasia of tumor cells and different degrees of rhabdomyoid differentiation. This is the first report of the ESR1::CITED2 fusion genes in UTROSCT, and one of the two patients had recurrence and metastasis. Compared with UTROSCT withESR1 rearrangement, UTROSCT with GREB1 rearrangement was more common in elderly patientsand was more likely to present with intramural masses, less sex cord differentiation, poor prognosis, and relapse and metastasis.

Transcript Level and Sequence Matching Are Key Determinants of Off-Target Effects in RNAi.

Double-stranded RNA (dsRNA) pesticides, those based on RNA interference (RNAi) technology utilizing dsRNA, have shown potential for pest control. However, the off-target effects of dsRNA pose limitations to the widespread application of RNAi and raise concerns regarding potential side effects on other beneficial organisms. The precise impact and underlying factors of these off-target effects are still not well understood. Here, we found that the transcript level and sequence matching jointly regulate off-target effects of dsRNA. The much lower expressed target genes were knocked down to a lesser extent than genes with higher expression levels, and the critical sequence identity of off-target effects is approximately 80%. Moreover, off-target effects could be triggered by a contiguous matching sequence length exceeding 15 nt as well as nearly perfectly matching sequences with one or two base mismatches exceeding 19 nt. Increasing the dosage of dsRNA leads to more severe off-target effects. However, the length of mismatched dsRNA, the choice of different RNAi targets, and the location of target sites within the same gene do not affect the severity of off-target effects. These parameters can be used to guide the design of possibly selective sequences for RNAi, optimize the specificity and efficiency of dsRNA, and facilitate practical applications of RNAi for pest control.

Measurement of the 5S1/2 to 5D5/2 two-photon clock transition frequency of rubidium-85 in high vacuum.

We present a scheme to precisely resolve the unperturbed line shape of an optical rubidium clock transition in a high vacuum, by which we avoided the systematic errors of "collision shift" and "modulation shift." The spectral resolution resolved by this scheme is significantly improved such that we can use "Zeeman broadening" to inspect the stray magnetic field, through which we were able to compensate the magnetic field inside the Rb cells to be below 10-3 Gauss. We thus update the absolute frequency of the clock transition and propose a standard operation procedure (SOP) for the clock self-calibration.

Knockdown of the glutamate-gated chloride channel gene decreases emamectin benzoate susceptibility in the fall armyworm, Spodoptera frugiperda.

Emamectin benzoate (EB), a derivative of avermectin, is the primary insecticide used to control the fall armyworm (FAW) in China. However, the specific molecular targets of EB against FAW remain unclear. In this study, we cloned the glutamate-gated chloride channel (GluCl) gene, which is known to be a primary molecular target for avermectin. We first investigated the transcript levels of SfGluCl in FAW and found that the expression level of SfGluCl in the head and nerve cord was significantly higher than that in other tissues. Furthermore, we found that the expression level of SfGluCl was significantly higher in eggs than that in other developmental stages, including larvae, pupae, and adults. Additionally, we identified three variable splice forms of SfGluCl in exons 3 and 9 and found that their splice frequencies remained unaffected by treatment with the LC50 of EB. RNAi mediated knockdown of SfGluCl showed a significant reduction of 42% and 65% after 48 and 72 h of dsRNA feeding, respectively. Importantly, knockdown of SfGluCl sifgnificantly reduced LC50 and LC90 EB treatment induced mortality of FAW larvae by 15% and 44%, respectively, compared to the control group feeding by dsEGFP. In contrast, there were no significant changes in the mortality of FAW larvae treated with the control insecticides chlorantraniliprole and spinetoram. Finally, molecular docking simulations revealed that EB bound to the large amino-terminal extracellular domain of SfGluCl by forming five hydrogen bonds, two alkyl hydrophobic interactions and one salt bridge. These findings strongly suggest that GluCl may serve as one of the molecular targets of EB in FAW, shedding light on the mode of action of this important insecticide.

[Corrigendum] Fully human VEGFR2 monoclonal antibody BC001 attenuates tumor angiogenesis and inhibits tumor growth.

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that, for the scratch wound assay experiments shown in Fig. 1 on p. 2413, the panels showing the '0 h' experiments for the respective incubations with VEGF or BC001 were apparently identical. The authors were able to re­examine their original data files, and realized that this figure had been inadverently assembled incorrectly. The revised version of Fig. 1, containing the correct data for the '0 h / BC001' panel, is shown below. Note that the revisions made to this figure do not affect the overall conclusions reported in the paper. The authors are grateful to the Editor of International Journal of Oncology for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [International Journal of Oncology 45: 2411­2420, 2014; DOI: 10.3892/ijo.2014.2690].

High-resolution Cs-Rb two-photon spectrometer for directly stabilizing a Ti:sapphire comb laser.

In this paper, we present a simple scheme for efficiently removing the residual Doppler background of a comb laser based two-photon spectrometer to be better than 10-3 background-to-signal ratio. We applied this scheme to stabilize the frequencies of a mode-locked Ti:sapphire laser directly referring to the cesium 6S-8S transition and rubidium 5S-5D transition. We suggest a standard operation procedure (SOP) for the fully direct comb laser stabilization and evaluate the frequency of two spectral lines at a certain temperature, by which we demonstrate an all-atomic-transition-based Ti:sapphire comb laser merely via a 6-cm glass cell.

Transdermal administration of ibuprofen-loaded hexagonal liquid crystal gel for enhancement of drug concentration in the uterus: in vitro and in vivo evaluation.

Primary dysmenorrhea is a common disease in women, and oral administration of Ibuprofen (IBU) is associated with first-pass effects and gastrointestinal irritation. Here, we developed ibuprofen-loaded hexagonal liquid crystal (IBU HLC) gel for transdermal administration. In this study, the structure of prepared IBU HLC was characterized using polarizing microscopey (PLM) and small angle X ray diffraction (SAXS). In vitro drug release behavior and percutaneous penetration were investigated, and drug transdermal behavior was observed by confocal laser scanning microscope (CLSM). Finally, the pharmacokinetic profile and tissue distribution were investigated after transdermal administration. The PLM and SAXS results showed that the inner structure of IBU HLC was hexagonal phase. Moreover, in vitro release, skin permeation and CLSM demonstrated that IBU HLC had an excellent sustained-release effect, and a good transdermal penetration effect accompanied by the combination of multiple percutaneous routes. Pharmacokinetic studies indicated that IBU entered the blood circulation through abdominal transdermal administration in small amounts, mainly entering the uterus, and had a certain targeting ability. In conclusion, the IBU HLC gel would be a promising sustained-release preparation for transdermal administration to relieve dysmenorrhea with a significant drug concentration in the uterus.

Structural basis of CDK3 activation by cyclin E1 and inhibition by dinaciclib.

Cell cycle transitions are controlled by multiple cell cycle regulators, especially CDKs. Several CDKs, including CDK1-4 and CDK6, promote cell cycle progression directly. Among them, CDK3 is critically important because it triggers the transitions of G0 to G1 and G1 to S phase through binding to cyclin C and cyclin E1, respectively. In contrast to its highly related homologs, the molecular basis of CDK3 activation remains elusive due to the lack of structural information of CDK3, particularly in cyclin bound form. Here we report the crystal structure of CDK3 in complex with cyclin E1 at 2.25 Å resolution. CDK3 resembles CDK2 in that both adopt a similar fold and bind cyclin E1 in a similar way. The structural discrepancy between CDK3 and CDK2 may reflect their substrate specificity. Profiling a panel of CDK inhibitors reveals that dinaciclib inhibits CDK3-cyclin E1 potently and specifically. The structure of CDK3-cyclin E1 bound to dinaciclib reveals the inhibitory mechanism. The structural and biochemical results uncover the mechanism of CDK3 activation by cyclin E1 and lays a foundation for structural-based drug design.

Control efficacy and joint toxicity of metaflumizone mixed with chlorantraniliprole or indoxacarb against the fall armyworm, Spodoptera frugiperda.

BACKGROUND: The fall armyworm (FAW), Spodoptera frugiperda is the main destructive pest of grain crops, and has led to substantial economic losses worldwide. Chemical pesticides are the most effective way to manage FAW. Here, a laboratory test using an artificial diet-incorporated assay was conducted to determine the toxicity of five insecticides and the joint effect of the binary combination insecticides to FAW larvae. A field plot test using foliar spray was carried out to assess the control efficacy of metaflumizone mixed with chlorantraniliprole or indoxacarb against FAW. RESULTS: The bioassay results showed that metaflumizone had a stronger insecticidal effect than indoxacarb toward FAW larvae. Furthermore, the mixture of metaflumizone and chlorantraniliprole in a volume ratio of 3:7 had the strongest synergistic effect against FAW, with a co-toxicity coefficient (CTC) of 317.18. The best synergistic effect for mixtures of metaflumizone and indoxacarb was observed at a 1:9 volume ratio, with a CTC of 185.98. However, there was an antagonistic effect of metaflumizone mixed with emamectin benzoate and with lufenuron, because the co-toxic factor was less than -20 at volume ratios of 8:2 and 9:1, respectively. According to the results of the field trial, metaflumizone mixed with chlorantraniliprole or indoxacarb at a 50% reduction of the application rate can effectively control FAW with efficacy ranging from 77.73% to 94.65% 1-7 days postapplication. CONCLUSION: Overall, our findings suggest that metaflumizone and its binary combination insecticides can be utilized in FAW integrated pest management programs. © 2022 Society of Chemical Industry.

Insights into the catalytic and regulatory mechanisms of dihydroflavonol 4-reductase, a key enzyme of anthocyanin synthesis in Zanthoxylum bungeanum.

Accumulation of anthocyanins largely determines the fruit color, and dihydroflavonol 4-reductase (DFR) is a key enzyme involved in the formation of anthocyanins. However, the catalytic and regulatory mechanisms of DFR are unclear. In this study, the gene encoding DFR from Zanthoxylum bungeanum Maxim. was cloned and ZbDFR was analyzed in detail. The ZbDFR accepted dihydrokaempferol, dihydroquercetin and dihydromyricetin as substrates. Flavonols such as myricetin, quercetin and kaempferol significantly inhibited the activity of ZbDFR, while quercitrin and isoquercitrin slightly increased the activity. Quercetin was a competitive inhibitor at low concentrations, and it had a combined effect of competitive and noncompetitive inhibition at high concentrations, which was consistent with ZbDFR having two inhibitor binding sites. In addition, the content of different types of flavonoids in Z. bungeanum peel at green, semi-red and red stage was analyzed, and the in vivo results could be explained by the regulation of ZbDFR activity in vitro. Site-directed mutagenesis combined with enzyme activity experiments showed that Ser128, Tyr163, Phe164 and Lys167 are the key catalytic amino acid residues. The Ser128, Tyr163 and Lys167 were crucial for the hydrogen transfer reaction, and mutation of these amino acids resulted in the loss of all or most of the activity. Phe164 was found to be important for the regulation of ZbDFR by flavonols. Accordingly, ZbDFR is a node at which flavonoids regulate the synthesis of anthocyanins and proanthocyanins.

High-quality genomes reveal significant genetic divergence and cryptic speciation in the model organism Folsomia candida (collembola).

The collembolan Folsomia candida Willem, 1902, is widely distributed throughout the world and has been frequently used as a test organism in soil ecology and ecotoxicology studies. However, it is questioned as an ideal "standard" because of differences in reproductive modes and cryptic genetic diversity between strains from various geographical origins. In this study, we obtained two high-quality chromosome-level genomes of F. candida, for a parthenogenetic strain (named FCDK, 219.08 Mb, 25,139 protein-coding genes) and a sexual strain (named FCSH, 153.09 Mb, 21,609 protein-coding genes), reannotated the genome of the parthenogenetic strain reported by Faddeeva-Vakhrusheva et al. in 2017 (named FCBL, 221.7 Mb, 25,980 protein-coding genes) and conducted comparative genomic analyses of the three strains. High genome similarities between FCDK and FCBL based on synteny, genome architecture, mitochondrial and nuclear gene sequences suggest that they are conspecific. The seven chromosomes of FCDK are each 25%-54% larger than the corresponding chromosomes of FCSH, showing obvious repetitive element expansions and large-scale inversions and translocations but no whole-genome duplication. The strain-specific genes, expanded gene families and genes in nonsyntenic chromosomal regions identified in FCDK are highly related to the broader environmental adaptation of parthenogenetic strains. In addition, FCDK has fewer strain-specific microRNAs than FCSH, and their mitochondrial and nuclear genes have diverged greatly. In conclusion, FCDK/FCBL and FCSH have accumulated independent genetic changes and evolved into distinct species after 10 million years ago. Our work provides important genomic resources for studying the mechanisms of rapidly cryptic speciation and soil arthropod adaptation to soil ecosystems.

[Preliminary Investigation of the Molecular Mechanism of Empagliflozin Suppressing Gastric Cancer Through Mammalian Target of Rapamycin]. / æ©æ ¼åˆ—å‡€é€šè¿‡é›·å¸•éœ‰ç´ é¶ç‚¹è›‹ç™½æŠ‘åˆ¶èƒƒç™Œçš„åˆ†å­æœºåˆ¶åˆæŽ¢.

Objective: To predict the intervention targets of empagliflozin (EMPA), a specific inhibitor of sodium-glucose cotransporter 2 (SGLT2), in gastric adenocarcinoma through comprehensive network pharmacology, and to validate the effects and the molecular mechanisms of EMPA through cellular and molecular biology experiments. Methods: Bioinformatics analysis of gastric adenocarcinoma was conducted to assess the correlation between gastric adenocarcinoma prognosis and SGLT2 expression. Network pharmacology was utilized to identify shared targets of EMPA and gastric adenocarcinoma. AGS cells, a human gastric adenocarcinoma cells line, were incubated with EMPA at different concentrations for 24 h and, then, cell proliferation was assessed using the CCK8 assay. After AGS cells were incubated with EMPA at the doses of 0, 3, and 6 mmol/L, real-time cell analysis (RTCA) and 5-ethynyl-2-deoxyuridine (EdU) incorporation were used to evaluate EMPA's inhibitory effects on the proliferation of the AGS cells. In addition, wound healing and Transwell assays were performed to assess the inhibitory effect of EMPA on the migration and invasion of the APC cells and Western blot analysis was conducted to examine the expression of mammalian target of rapamycin (mTOR) and phosphorylated mTOR (p-mTOR). BALB/c (nu/nu) nude mice were implanted with 5×106 AGS cells in the axilla. The mice were divided into three groups, a control group, a low-dose group, and a high-dose group, each consisting of 7 mice. After one week, the control group received daily intraperitoneal injections of normal saline, while the low-dose group and high-dose group received daily intraperitoneal injections of EMPA at the doses of 3 mg/kg and 5 mg/kg, respectively. The tumor volume was measured one week after the drug intervention started. Results: Gastric adenocarcinoma patients with low expression of SGLT2 exhibited longer survival time and higher survival rate than those with high expression of SGLT2 did. A total of 104 EMPA-related potential targets and 2028 targets associated with gastric adenocarcinoma were identified. Among these, 45 targets associated with gastric adenocarcinoma overlapped with potential targets of EMPA. Further analysis revealed 10 relevant pathways and 4 core genes. The core genes were cyclin-dependent kinase 4 (CDK4), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), mTOR, and cyclin E1 (CCNE1). CCK-8 assay revealed that EMPA at concentrations ranging from 0.39 to 50 mmol/L effectively inhibited the proliferation of AGS cells. RTCA results indicated a downward shift in the cell growth curve. In comparison to the findings for the control group, EdU assay demonstrated that EMPA at the concentrations of 3 mmol/L and 6 mmol/L significantly inhibited AGS cell proliferation (P<0.05). Results from wound healing and Transwell assays indicated a decrease in the levels of cell migration and invasion (P<0.05) and, notably, there was a significant difference between the high and low-dose EMPA groups (P<0.05). Western blot showed no statistically significant difference in the expression of total mTOR protein between the groups. However, the expression of p-mTOR in the 3 mmol/L and 6 mmol/L EMPA groups decreased compared to that of the control group (P<0.05), with the 6 mmol/L EMPA group exhibiting a more pronounced reduction (P<0.05). Nude mice xenograft tumor experiment demonstrated that, compared to that of the control group, the tumor volumes in the EMPA-treatment groups were significantly reduced (P<0.05), with the high-dose group showing a more pronounced reduction (P<0.05). Conclusion: EMPA inhibits the abnormal proliferation and migration of gastric adenocarcinoma cells, potentially through the modulation of mTOR protein activation. This study provides new potential medication and intervention targets for gastric adenocarcinoma treatment.

Research progress of ProTide technology and its application in the development of antiviral drugs / 药学学报

ProTide technology is a kind of prodrug design strategy invented by the team of Christopher McGuigan. ProTides are aryloxyphosphoramidates (or aryloxyphosphonamidates) which contain a phosphorus atom combined with an amino acid ester and an aryloxy group. These prodrugs can efficiently cross the cell membrane and escape from the first rate-limiting step of phosphorylation, which afford effective solutions to the drawbacks of current nucleoside analogues. At present, ProTide technology has been extensively applied in the field of antiviral research. It has been successful in providing a number of approved drugs and clinical candidates, such as sofosbuvir and so much more, highlighting the promising future in drug discovery. This review summarizes the brief history and characteristics of ProTide technology, as well as its application in the exploration of antiviral drugs.

External rhinoplasty based on the classification of alar retraction associating with exposure of the nostrils / 中华耳鼻咽喉头颈外科杂志

Objective: To introduce a classification of alar retraction, and to discuss the therapeutic strategy of alar retraction with cartilage graft and the satisfaction evaluation of patients after operation. Methods: A retrospective analysis was performed on 88 patients with alar retraction admitted to the Department of Plastic and Aesthetic (Burn) Surgery, the Second Xiangya Hospital of Central South University from January 2015 to December 2020, including 20 males and 68 females, aged 20 to 48 years, with an average age of 28.98 years. All patients underwent external rhinoplasty according to a series of treatment plans determined by the classification of alar retraction based on nostril exposure. Visual Analogue Scale (VAS) and Rhinoplasty Outcomes Evaluation (ROE) were used to conduct satisfaction survey before and 12 months after operation. Wilcoxon signed-rank test was used to analyze patient satisfaction. Results: A total of 88 patients were included in this study. According to the classification of alar retraction based on nostril exposure, 45 cases were mild, 23 cases were moderate, and 20 cases were severe. There were 16 cases of unilateral and 72 cases of bilateral alar retraction. The patients were followed up for 12 to 18 months, with an average of 13.37 months. The VAS score and ROE score after each type of surgery were higher than those before surgery, with statistically significant (all P<0.05). Among them, the difference in VAS score (6.75±1.29) and in ROE satisfaction (67.70±7.38) of patients with severe alar retraction were the most significant improvement. Conclusion: The classification of alar retraction based on nostril exposure in the frontal view can comprehensively evaluate the severity of alar retraction, and makes the treatment algorithms systematic and comprehensive. The satisfaction of patients is relatively high.

Imaging measurement and analysis of related indexes of variation of femoral head rotation center / 中国骨伤

OBJECTIVE@#To provide guidance for hip replacement by analyzing the variation of femoral head rotation center in different hip diseases.@*METHODS@#A total of 5 459 patients were collected from March 2016 to June 2021, who took positive and proportional plain films of both hips for various reasons. The relative position between the rotation center of the femoral head and the apex of the greater trochanter was measured. The positive variation is more than 2 mm above the top of the great trochanter, and the negative variation is more than 2 mm below the top of the great trochanter. A total of 831 patients with variation of femoral head rotation center were collected and were divided into 4 groups according to different diseases, and the variation was counted respectively. There were 15 cases in the normal group involving 10 cases of positive variation and 5 cases of negative variation. There were 145 cases of avascular necrosis of femoral head involving 25 cases of positive variation and 120 cases of negative variation. There were 346 cases of congenital hip dysplasia involving 225 cases of positive variation(including 25 cases of typeⅠ, 70 cases of type Ⅱ, 115 cases of type Ⅲ and 15 cases of type Ⅳ), and 121 cases of negative variation(including 50 cases of crowe typeⅠ, 60 cases of typeⅡ, 10 cases of type Ⅲ and 1 case of type Ⅳ). There were 325 cases of hip osteoarthritis group involving 45 cases of positive variation and 280 cases of negative variation.@*RESULTS@#There was significant difference in variation of femoral head rotation center among the four groups(P<0.05). There was significant difference in variation of femoral head rotation center among different types of congenital hip dysplasia(P<0.05). There were significant differences in cervical trunk angle and eccentricity among different variations of femoral head rotation center(P<0.05).@*CONCLUSION@#The variation of femoral head rotation center is related to cervical trunk angle and eccentricity. The variation of femoral head rotation center is an important factor in hip diseases. The variation of femoral head rotation center is different in different hip diseases. Avascular necrosis of the femoral head and osteoarthritis of the hip were mostly negative variations. With the aggravation of congenital hip dysplasia, the variation of femoral head rotation center gradually changed from negative variation to positive variation.The variation of femoral head rotation center should be paid attention to in the preoperative planning of hip arthroplasty. It is of great significance to select the appropriate prosthesis and place the prosthesis accurately.

Propensity score-matched study of uni-condylar arthroplasty in elderly patients with knee osteoarthritis / 中国骨伤

OBJECTIVE@#To investigate the clinical efficacy of unicompartmental knee arthroplasty (UKA) in the treatment of knee osteoarthritis in patients over 75 years old.@*METHODS@#The clinical efficacy of primary fixed platform UKA in patients with osteoarthritis, was retrospectively analyzed from October 2014 to November 2020. Age, body mass index (BMI), range of motion (ROM), preoperative joint function score, the quality of life score and other preoperative indicators were measured by propensity score matching (PSM). The patients were divided into elderly group (≥75 years old) and control group (<75 years old). Oxford knee score(OKS), Western Ontario McMaster Universities osteoarthritis index(WOMAC), Short Form-12 including physical component summary (PCS), mental component summary(MCS), minimal clinically important difference(MCID ) and clinical complications were evaluated preoperatively and postoperatively.@*RESULTS@#A total of 514 patients were analyzed, 428 patients fulfilled the inclusion criteria. A propensity-score matching study was conducted to eliminate confounding factors. After 1∶2 propensity match, there were 84 patients in elderly group (≥75 years), age ranged from 75 to 88 years old, with an average of (78.79±3.08) years old, and 168 patients in control group (<75 years), age ranged from 47 to 74 years old, with an average of (64.10±5.96)years old. The follow-up duration of two groups ranged from 12 to 84 months with an average of (29.35±16.52) months in elderly group, and 12 to 85 months with an average of (31.83±17.34) months in control group. There was only significant difference in age between the elderly and control groups preoperatively (P<0.01). Postoperatively, the elderly group showed significantly higher WOMAC (P<0.01) and lower SF-12 PCS scores (P<0.01) as compared to the control group. There was no significant difference between the elderly group and the control group in knee range of motion, OKS and the proportion of each scoring system reaching the minimum clinical difference value (P>0.05). In the aspect of preperative complications, the elderly group exhibited more surgical site complications and postoperative delirium compared to control group(P<0.05). The differences in other indicators including deep vein thrombosis, acute urinary retention, cardiovascular events, cerebrovascular events and radiolucent lines around prothesis were not statistically significant(P>0.05).@*CONCLUSION@#UKA in the treatment of elderly patients over 75 years old with knee osteoarthritis was safe and feasible, and could obtain satisfactory short-term efficacy.

Melanogenesis of quality markers in Vernonia anthelmintica Injection based on UPLC-Q-TOF-MS combined network pharmacology / 中国中药杂志

This study aimed to evaluate the biological effect and mechanism of Vernonia anthelmintica Injection(VAI) on melanin accumulation. The in vivo depigmentation model was induced by propylthiouracil(PTU) in zebrafish, and the effect of VAI on melanin accumulation was evaluated based on the in vitro B16F10 cell model. The chemical composition of VAI was identified according to the high-performance liquid chromatography quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS). Network pharmaco-logy was applied to predict potential targets and pathways of VAI. A "VAI component-target-pathway" network was established, and the pharmacodynamic molecules were screened out based on the topological characteristics of the network. The binding of active molecules to key targets was verified by molecular docking. The results showed that VAI promoted tyrosinase activity and melanin production in B16F10 cells in a dose-and time-dependent manner and could restore the melanin in the body of the zebrafish model. Fifty-six compounds were identified from VAI, including flavonoids(15/56), terpenoids(10/56), phenolic acids(9/56), fatty acids(9/56), steroids(6/56), and others(7/56). Network pharmacological analysis screened four potential quality markers, including apigenin, chrysoeriol, syringaresinol, and butein, involving 61 targets and 65 pathways, and molecular docking verified their binding to TYR, NFE2L2, CASP3, MAPK1, MAPK8, and MAPK14. It was found that the mRNA expression of MITF, TYR, TYRP1, and DCT in B16F10 cells was promoted. By UPLC-Q-TOF-MS and network pharmacology, this study determined the material basis of VAI against vitiligo, screened apigenin, chrysoeriol, syringaresinol, and butein as the quality markers of VAI, and verified the efficacy and internal mechanism of melanogenesis, providing a basis for quality control and further clinical research.

Analysis of WRKY transcription factor family based on full-length transcriptome sequencing in Polygonatum cyrtonema / 中国中药杂志

WRKY transcription factor family plays an important role in plant growth and development, secondary metabolite synthesis, and biotic and abiotic stress responses. The present study performed full-length transcriptome sequencing of Polygonatum cyrtonema by virtue of the PacBio SMRT high-throughput platform, identified the WRKY family by bioinformatics methods, and analyzed the physicochemical properties, subcellular localization, phylogeny, and conserved motifs. The results showed that 30.69 Gb nucleotide bases and 89 564 transcripts were obtained after redundancy removal. These transcripts had a mean length of 2 060 bp and an N50 value of 3 156 bp. Based on the full-length transcriptome sequencing data, 64 candidate proteins were selected from the WRKY transcription factor family, with the protein size of 92-1 027 aa, the relative molecular mass of 10 377.85-115 779.48 kDa, and the isoelectric point of 4.49-9.84. These WRKY family members were mostly located in the nucleus and belonged to the hydrophobic proteins. According to the phylogenetic analysis of WRKY family in P. cyrtonema and Arabidopsis thaliana, all WRKY family members were clustered into seven subfamilies and WRKY proteins from P. cyrtonema were distributed in different numbers in these seven subgroups. Expression pattern analysis confirmed that 40 WRKY family members had distinct expression patterns in the rhizomes of 1-and 3-year-old P. cyrtonema. Except for PcWRKY39, the expression of 39 WRKY family members was down-regulated in 3-year-old samples. In conclusion, this study provides abundant reference data for genetic research on P. cyrtonema and lays a foundation for the in-depth investigation of the biological functions of the WRKY family.