An integrative approach to protein sequence design through multiobjective optimization.

With recent methodological advances in the field of computational protein design, in particular those based on deep learning, there is an increasing need for frameworks that allow for coherent, direct integration of different models and objective functions into the generative design process. Here we demonstrate how evolutionary multiobjective optimization techniques can be adapted to provide such an approach. With the established Non-dominated Sorting Genetic Algorithm II (NSGA-II) as the optimization framework, we use AlphaFold2 and ProteinMPNN confidence metrics to define the objective space, and a mutation operator composed of ESM-1v and ProteinMPNN to rank and then redesign the least favorable positions. Using the two-state design problem of the foldswitching protein RfaH as an in-depth case study, and PapD and calmodulin as examples of higher-dimensional design problems, we show that the evolutionary multiobjective optimization approach leads to significant reduction in the bias and variance in RfaH native sequence recovery, compared to a direct application of ProteinMPNN. We suggest that this improvement is due to three factors: (i) the use of an informative mutation operator that accelerates the sequence space exploration, (ii) the parallel, iterative design process inherent to the genetic algorithm that improves upon the ProteinMPNN autoregressive sequence decoding scheme, and (iii) the explicit approximation of the Pareto front that leads to optimal design candidates representing diverse tradeoff conditions. We anticipate this approach to be readily adaptable to different models and broadly relevant for protein design tasks with complex specifications.

Development of a QuEChERS-HPLC-FLD Procedure for the Simultaneous Detection of Residues of Florfenicol, Its Metabolite Florfenicol Amine, and Three Fluoroquinolones in Eggs.

A method utilizing high-performance liquid chromatography-fluorescence detection (HPLC-FLD) has been developed and refined for the simultaneous detection of florfenicol (FF) and its metabolite florfenicol amine (FFA) along with three fluoroquinolone (ciprofloxacin (CIP), enrofloxacin (ENR), and sarafloxacin (SAR)) residues in different parts of eggs (whole egg, egg yolk, and egg albumen). The QuEChERS ("Quick, easy, cheap, effective, rugged, and safe") procedure utilized 0.1 M disodium EDTA solution, water, and acetonitrile as extractants; sodium sulfate, sodium chloride, and trisodium citrate as dehydrating salts; and N-propylethylenediamine and C18 as adsorbents. A dual-channel FLD method was utilized to analyze the target compounds using an XBridge BEH C18 chromatographic column (4.6 mm × 150 mm, 5 µm). The mobile phase was employed isocratically using a solution of 0.01 M sodium dihydrogen phosphate, 0.005 M sodium dodecyl sulfate, and 0.1% triethylamine (pH 4.8) in combination with acetonitrile at a ratio of 65:35 (V/V). The limits of detection (LOD) and quantification (LOQ) of the analytes ranged from 0.03 to 1.5 µg/kg and from 0.1 to 5.0 µg/kg, respectively. The recoveries of the analytes in the blank egg samples ranged from 71.9% to 94.8% when reference standard concentrations of the LOQ, half of the maximum residual limit (MRL), MRL, and twice the MRL were added. The parameters of the presented protocol were validated and subsequently applied to the analysis of real samples, demonstrating the applicability and reliability of the method.

An integrative approach to protein sequence design through multiobjective optimization.

With recent methodological advances in the field of computational protein design, in particular those based on deep learning, there is an increasing need for frameworks that allow for coherent, direct integration of different models and objective functions into the generative design process. Here we demonstrate how evolutionary multiobjective optimization techniques can be adapted to provide such an approach. With the established Non-dominated Sorting Genetic Algorithm II (NSGA-II) as the optimization framework, we use AlphaFold2 and ProteinMPNN confidence metrics to define the objective space, and a mutation operator composed of ESM-1v and ProteinMPNN to rank and then redesign the least favorable positions. Using the multistate design problem of the foldswitching protein RfaH as an in-depth case study, we show that the evolutionary multiobjective optimization approach leads to significant reduction in the bias and variance in RfaH native sequence recovery, compared to a direct application of ProteinMPNN. We suggest that this improvement is due to three factors: (i) the use of an informative mutation operator that accelerates the sequence space exploration, (ii) the parallel, iterative design process inherent to the genetic algorithm that improves upon the ProteinMPNN autoregressive sequence decoding scheme, and (iii) the explicit approximation of the Pareto front that leads to optimal design candidates representing diverse tradeoff conditions. We anticipate this approach to be readily adaptable to different models and broadly relevant for protein design tasks with complex specifications.

VISTA antibody-loaded Fe3O4@TiO2 nanoparticles for sonodynamic therapy-synergistic immune checkpoint therapy of pancreatic cancer.

Breaking the poor permeability of immune checkpoint inhibitors (ICIs) caused by the stromal barrier and reversing the immunosuppressive microenvironment are significant challenges in pancreatic cancer immunotherapy. In this study, we synthesized core-shell Fe3O4@TiO2 nanoparticles to act as carriers for loading VISTA monoclonal antibodies to form Fe3O4@TiO2@VISTAmAb (FTV). The nanoparticles are designed to target the overexpressed ICIs VISTA in pancreatic cancer, aiming to improve magnetic resonance imaging-guided sonodynamic therapy (SDT)-facilitated immunotherapy. Laser confocal microscopy and flow cytometry results demonstrate that FTV nanoparticles are specifically recognized and phagocytosed by Panc-2 cells. In vivo experiments reveal that ultrasound-triggered TiO2 SDT can induce tumor immunogenic cell death (ICD) and recruit T-cell infiltration within the tumor microenvironment by releasing damage-associated molecular patterns (DAMPs). Furthermore, ultrasound loosens the dense fibrous stroma surrounding the pancreatic tumor and increases vascular density, facilitating immune therapeutic efficiency. In summary, our study demonstrates that FTV nanoparticles hold great promise for synergistic SDT and immunotherapy in pancreatic cancer.

Temperature-Dependent Fold-Switching Mechanism of the Circadian Clock Protein KaiB.

The oscillator of the cyanobacterial circadian clock relies on the ability of the KaiB protein to switch reversibly between a stable ground-state fold (gsKaiB) and an unstable fold-switched fold (fsKaiB). Rare fold-switching events by KaiB provide a critical delay in the negative feedback loop of this post-translational oscillator. In this study, we experimentally and computationally investigate the temperature dependence of fold switching and its mechanism. We demonstrate that the stability of gsKaiB increases with temperature compared to fsKaiB and that the Q10 value for the gsKaiB → fsKaiB transition is nearly three times smaller than that for the reverse transition. Simulations and native-state hydrogen-deuterium exchange NMR experiments suggest that fold switching can involve both subglobally and near-globally unfolded intermediates. The simulations predict that the transition state for fold switching coincides with isomerization of conserved prolines in the most rapidly exchanging region, and we confirm experimentally that proline isomerization is a rate-limiting step for fold switching. We explore the implications of our results for temperature compensation, a hallmark of circadian clocks, through a kinetic model.

Fetal Hyperthyroidism with Maternal Hypothyroidism: Two Cases of Intrauterine Therapy.

Fetal hyperthyroidism can occur secondary to maternal autoimmune hyperthyroidism. The thyroid-stimulating hormone receptor antibody (TRAb) transferred from the mother to the fetus stimulates the fetal thyroid and causes fetal thyrotoxicosis. Fetuses with this condition are difficult to detect, especially after maternal Graves disease therapy. Here, we present two cases of fetal hyperthyroidism with maternal hypothyroidism and review the assessment and intrauterine therapy for fetal hyperthyroidism. Both women were referred at 22+ and 23+ weeks of gestation with abnormal ultrasound findings, including fetal heart enlargement, pericardial effusion, and fetal tachycardia. Both women had a history of Graves disease while in a state of hypothyroidism with a high titer of TRAb. A sonographic examination showed a diffusely enlarged fetal thyroid with abundant blood flow. Invasive prenatal testing revealed no significant chromosomal aberration. Low fetal serum TSH and high TRAb levels were detected in the cord blood. Fetal hyperthyroidism was considered, and maternal oral methimazole (MMI) was administered as intrauterine therapy, with the slowing of fetal tachycardia, a reduction in fetal heart enlargement, and thyroid hyperemia. During therapy, maternal thyroid function was monitored, and the dosage of maternal levothyroxine was adjusted accordingly. Both women delivered spontaneously at 36+ weeks of gestation, and neonatal hyperthyroidism was confirmed in both newborns. After methimazole and propranolol drug treatment with levothyroxine for 8 and 12 months, both babies became euthyroid with normal growth and development.

Effect of LPCAT1 on biological behavior of cervical cancer based on β-catenin/Slug signaling pathway / 临床与实验病理学杂志

Purpose To observation the relationship be-tween the β-catenin/Slug signal specific inhibitor FH535 and EMT,and to explore the role of LPCAT1 in regulating the inva-sion,metastasis,and growth of cervical cancer cells.Methods Hela cells were transfected with sh-NC and sh-LPCAT1,and SiHa cells were transfected with Vector group and LPCAT1 over-expression plasmid.SiHa cells were divided into control group(Con),LPCAT1 group,LPCAT1+FH535 group and FH535 group.The proliferation of cervical cancer cells was detected by CCK-8 analysis and colony formation test.The metastasis and invasion ability of cervical cancer cells were detected by wound healing test and Transwell test.Western blot was used to analyze the expression of LPCAT1,β-catenin/Slug signaling pathway and EMT-related proteins in cells.Results Compared with Vector group,the cell viability,colony number,migration and invasion number of SiHa cells in LPCAT1 group increased signif-icantly(P＜0.05).Compared with sh-NC group,the cell via-bility,colony number,migration and invasion number of Hela cells in sh-LPCAT1 group decreased significantly(P＜0.05).Compared with LPCAT1 group,the levels of Wnt4(1.18±0.05 vs 0.80±0.06),β-catenin(1.05±0.08 vs 0.77±0.05),Slug(1.13±0.06 vs 0.28±0.02),Cyclin D1(0.99±0.06 vs 0.44±0.02),N-cadherin(0.91±0.07 vs 0.46±0.03)and vimentin(0.95±0.06 vs 0.49±0.03)in SiHa cells in LPCAT1+FH535 group decreased significantly(P＜0.05),and the level of E-cadherin(0.44±0.03 vs 0.58±0.03)in-creased significantly(P＜0.05).In addition,compared with LPCAT1 group,the number of colonies(224±15 vs 146±11),migration(85±3vs51±4)and invasive(166±10 vs 90±5)cells of SiHa cells in LPCAT1+FH535 group decreased signifi-cantly(P＜0.05).Conclusion The increase of LPCAT1 ex-pression may promote the metastasis and progress of CC by acti-vating β-catenin/Slug signaling pathway,and LPCAT1 may be a potential marker for predicting CC metastasis.

Association between index-ring finger length ratio and polymorphisms of 6 phalange-bone development related genes / 解剖学报

Objective To investigate the association of 13 single nucleotide polymorphism(SNP)sites in 6 phalange-bone development related genes[fibroblast growth factor receptor 2(FGFR2),indian hedgehog signaling molecule(IHH),Msh homeobox 1(MSX1),Runx family transcription factor 2(RUNX2),SRY-box transcription factor 9(SOX9),Wnt family member 5A(WNT5A)]with human index-ring finger length ratio(2D∶4D).Methods Digital cameras were used to take frontal photographs of the hands of 731 college students(358 males and 373 females)in Ningxia,and image analysis software was used to mark anatomical points and measure finger lengths of index(2th)and ring(4th);genotyping of 13 SNP sites(rs1047057,rs755793,rs41258305,rs3731881,rs3100776,rs12532,rs3821949,rs45585135,rs3749863,rs1042667,rs12601701,rs1829556,rs3732750)for 6 genes by multiplex PCR;One-Way ANOVA or independent sample t-test indirectly assessed the association between 2D∶4D and 13 SNP sites.Results Both left and right hand 2D∶4D were significantly higher in females than males in Ningxia college students(all P<0.01);no statistically significant differences in genotype and allele frequencies of the 13 SNP sites among different sexes(all P>0.05);among different sexes,male left hand 2D∶4D was significantly associated with the genotype of SOX9 gene rs12601701 site(P<0.05)and right hand 2D∶4D was significantly associated with the genotype of WNT5A gene rs1829556 site(P<0.05);the female right hand 2D∶4D was significantly associated with the MSX1 gene rs12532(P<0.01)and rs3821949(P<0.05)sites genotypes.Conclusion SOX9(rs12601701),WNT5A(rs1829556)and MSX1(rs12532 and rs3821949)gene polymorphisms may be associated with the formation of 2D∶4D in Ningxia population.

Association between index finger and ring finger length ratios and polymorphism of homeobox A11 gene locus among Ningxia college students / 解剖学报

Objective To investigate the association between the index finger and ring finger length ratio (2D ∶ 4D) and of four loci (rs6461992‚ rs6968828‚ rs7801581‚ rs17427875) polymorphism of homeobox (HOX) A11 gene among Ningxia college students. Methods Digit camera was used to collect frontal hand photos of 667 Han college students (348 males and 319 females) from Ningxia province; Image analysis software was used to mark the anatomical points and measure finger lengths of the index and ring fingers of both hands; multiplex PCR was used to detect each locus polymorphisms of HOXA11 gene; statistical software was used to compare and analyze the differences and associations of 2D ∶4D and gene polymorphisms between different genders. Results Among Ningxia Han college students‚ both left hand and right hand 2D ∶ 4D were significantly higher in females than those of in males (all P< 0. 05)‚ and there were no significant sex differences in right-left hand 2D ∶4D; the genotypes and allele frequencies of rs7801581 locus of HOXA11 gene differed significantly between genders (all P < 0. 05)‚ and none of the other locus polymorphisms showed any significant sex differences; only female left hand 2D ∶4D was significantly associated with rs6461992 locus genotype in the relationship between 2D ∶4D and HOXA11 polymorphisms (P<0. 05). Conclusion There were significant sex differences in 2D ∶ 4D among Han college students in Ningxia‚ and the rs6461992 locus polymorphism of HOXA11 gene may be associated with the formation of 2D ∶4D in females.

Analysis of amino acid and protein components of commercial swim-bladders / 中成药

AIM To study the amino acids and proteins in 16 batches of commercial fish swim-bladders with different origins.METHODS A high performance liquid chromatography method based on pre-column derivatization using 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate(AQC)was developed for the determination of contents and components of 17 amino acids in fish swim-bladders.Sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE)was performed to analyze the molecular weight distribution of proteins from different fish swim-bladders,and proteins in fish swim-bladders were identified by proteomics method.RESULTS The result showed that the determination of 17 amino acids had a good linear relationship(R2≥0.998 0).The average recovery rate was 85.62%-109.60%and the relative standard deviations of precision,stability and repeatability were less than 3.5%.The total content of the 17 amino acids in 16 batches of fish swim-bladders ranged from 468.31 mg/g to 620.05 mg/g.A total of 688 proteins including 11 collagens were identified from 16 batches of fish swim-bladder samples and a plenty of low-abundance proteins at 52-95 kDa were also detected in fish swim-bladders by SDS-PAGE.CONCLUSION This study provides a good reference for the quality evaluation and further utilization of fish swim-bladders.

The development trend of scientific research in the field of maternal and child health in the new era in China / 中国实用护理杂志

This commentary summarized the development trend of scientific research in the field of maternal and child health in China, based on the requirements of scientific innovation in the field of health care in China and the development goals of maternal and child health in the next ten years. Scientific research should be based on China's reality and solve China's problems; based on evidence-based evidence and promote its application and promotion; conduct interdisciplinary cooperation and promote the integrated development of disciplines; focus on academic frontiers and broaden international horizons.

Analytical performance verification protocols and specifications of CD34 +cell enumeration by flow cytometry / 中华检验医学杂志

Objective:To investigate the analytical performance verification protocols and performance specifications of CD34+cell enumeration by flow cytometry for clinical laboratories.Methods:According to international guidelines and National Health Standard of China, we designed the performance verification protocols of CD34 +cell enumeration (including percent count and absolute count) by flow cytometry. Four quality assessment materials, three leukapheresis products and three samples of peripheral blood were selected to verify the precision, linearity, carryover, trueness and accuracy of FACSCanto Ⅱ measurement system, and the assessment criterion was set according to the detection technologies of clinical laboratories. Results:The CVs of intra-run precision of percent count and absolute count were 2.5% to 8.9% and 3.0% to 9.0%; the CVs of inter-run precision were 2.8% to 10.5% and 3.8% to 9.9%, respectively. The slopes of linearity regression equation of low range (3.6/μl to 123.6/μl) and high range (113.2/μl to 1196.3/μl) were 0.993 2 and 0.965 2, and R2 were 0.999 6 and 0.993 9, and the biases were -8.67% to 0.22%. The carryover of percent and absolute count were 0.07% and 0.00%. When percent count≤0.2% or absolute count≤20/μl, the absolute biases of trueness were in the range of ±0.006% or ±0.5/μl, and the absolute biases of accuracy were in the range of ±0.02% or ±0.9/μl; when percent count>0.2% or absolute count>20/μl, the relative biases of trueness were in the range of ±5.65%, and the relative biases of accuracy were in the range of ±8.19%. The verification results met the assessment criterion set in this study. Conclusions:The performance verification protocols and assessment criterion formulated in this study not only conform to the recommendations of domestic and foreign guidelines, but also conform to state of the detection technologies of native clinical laboratories, which can be taken as a reference of performance verification for clinical laboratories.

Body water percentage from childhood to old age

Total body water (TBW) increases with growth, but the body water percentage (TBW%) decreases with aging. The objective of our study was to delineate TBW% in males and females by bioelectrical impedance analysis (BIA) from early childhood to old age. Methods: We enrolled 545 participants aged 3 to 98 years (258 male, 287 female). Among the participants, 256 had a normal weight and 289 were overweight. The TBW was measured by BIA, and TBW% was derived by dividing the TBW (L) value by body weight (kg). For analysis, we divided participants into the four age groups of 3–10, 11–20, 21–60, and ≥61 years. Results: In normal-weight subjects, the TBW% was similar at 62% between males and females in the 3–10-year group. It remained unchanged in males until and through adult life, then decreased to 57% in the ≥61-year group. In normal-weight female subjects, the TBW% decreased to 55% in the 11–20-year group, remained relatively unaltered in the 21–60-year group, then decreased to 50% in the ≥61-year group. In overweight subjects, the TBW% values in males, as well as females, were significantly lower as compared to those with normal weight. Conclusion: Our study showed that the TBW% in normal-weight males changes very little from early childhood to adult life compared to that of females, who showed a decrease in TBW% during the pubertal years. In normal-weight subjects of both sexes, the TBW% decreased after the age of 60 years. Overweight subjects had significantly lower TBW% as compared to those with normal weight.

Digit ratio in men with schizophrenia / 解剖学报

Objective To investigate the relationship between digit ratio and schizophrenia in men from Ningxia Han nationality. Methods Using anthropometry, digital camera was used to obtain finger photographs of both hands of 216 male subjects (nonnal control; 116, schizophrenia patient; 100). The anatomical points were marked and the length of each finger of both hands were measured by computer image analysis software (Image-Pro Plus 6 . 0 ) . Differences of the mean digit ratio of left and right hand 2D:3D, 2D:4D, 2D:5D, 3D:4D, 3D:5D, 4D:5D between the control group and the patient group were compared. The correlation between 2D :4D and onset age in the patient group were analyzed. Results Except for left and right hand 3D :4D, digit ratios in patient group were significantly higher than those in control group (2D :4D and 3D :5D in both hands, right hand 3D :5D, p all0. 05). Conclusion Digit ratio is related to the occurrence of schizophrenia in Ningxia Han male.

Association between hydroxysteroid dehydrogenases gene family single-nucleotide polymorphisms and digit ratio / 解剖学报

Objective To investigate the association between 8 single-nucleotide polymorphisms (SNPs) of hydroxysteroid dehydrogenase (HSD) gene family and human digit ratio (2D ∶ 4D). Methods Randomly selected 808 college students (400 males and 408 females) as subjects, the digit ratio of left and right fingers were measured and calculated using computer image software. Eight SNPs (rs1000283, rs2236903, rs5479, rs56303414, rs676387, rs4445895, rs2066474, rs8190478) in HSD11B and HSD17B gene families were genotyped by multiplex PCR. The association between 2D ∶4D and different genotypes was analyzed by One-Way ANOVA. Results Female left hand(L)2D ∶ 3D, L2D ∶4D, L3D ∶4D, right hand(R)2D ∶4D, R2D ∶5D were significantly higher than male (P0. 05). The genotypes frequency of the 8 SNPs were not significantly associated with digit ratio (2D ∶4D) in both males and females (P>0. 05). Conclusion There are significant gender differences in digit ratio in Ningxia Han college students, but there is no correlation between digit ratio and 8 SNPs in HSD11B and HSD17B gene families, suggesting that HSD11B and HSD17B gene families may have nothing to do with the formation of human digit ratio.

Design of children's growth and development data traceability system based on blockchain / 医疗卫生装备

Objective To design a blockchain-based child growth and development data traceability system.Methods A blockchain-based child growth and development data traceability system was designed with B/S architecture,programmed with PHP,HTML5 and JavaScript languages and constructed with the technologies of blockchain data structure,digital signature,hash function and peer-to-peer network,which was composed of five functional modules for user management,patient management,medical examination management,blockchain management and system log.Results The system recorded and shared child growth and development data,realizing traceability of child growth and development data.Conclusion The system developed gains advantages in easy operation,decentralization,high security and privacy,solves the problems in child growth and development data traceability and provides assistance to pediatricians effectively.[Chinese Medical Equipment Journal,2023,44(10):38-43]

Effects of Apelin-13/putative receptor protein related to AT1 homodimer on behaviors of human umbilical vein endothelial cells / 中国药理学通报

Aim To explore the effects of putative receptor protein related to ATI (APJ) homodimer on the behaviors-the proliferation, migration and tube formation of human umbilical vein endothelial cells (HU-VECs). Methods HUVECs at logarithmic growth stage were randomly divided into PBS, Apelin-13 + TM1 (APJ monomer group) and Apelin-13 + PBS group (APJ homodimer group). Western blot and Matrix-Assisted Laser Desorption/Ionization Time of Fligh Mass Spectrometry (MALDI-TOF MS) were used to detect the expression of APJ and APJ homodimer in HUVECs, respectively. Real-Time Cell Analyzers (RT-CA) was used to detect the concentration of the maximum effect of Apelin-13. Cell viability was detected by CCK-8. The cell migration ability was detected by scratch test, and the number of tubes formed on matri-gel that made artificial basement membrane was counted. Results Western blot and MALDI-TOF MS showed that APJ and APJ homodimer were expressed in HUVECs. The EC50 of Apelin-13 was 2.26 x 10

Clinical efficacy of fire needling combined with cupping therapy on herpes zoster of acute stage and the effect on Th17/Treg cellular immune balance / 中国针灸

OBJECTIVE@#To compare the clinical efficacy between the combined therapy of fire needling and cupping, and western medication on herpes zoster of acute stage, as well as the effects on Th17 and Treg cells and inflammatory factors, i.e. IL-10 and IL-17 in the peripheral blood.@*METHODS@#Eighty patients with herpes zoster of acute stage were randomly divided into a combined therapy (fire needling plus cupping) group and a western medication group, 40 cases in each one. In the combined therapy group, the pricking and scattering techniques with fire needle were used at ashi points and Jiaji (EX-B 2) corresponding to the affected spinal segments; afterwards, cupping therapy was delivered. The combined treatment was given once daily. In the western medication group, valaciclovir hydrochloride tablet and vitamin B1 tablet were administered orally. The duration of treatment in each group was 10 days. Before each treatment from day 1 to day 10 and on day 11 , the score of symptoms and physical signs was observed in the two groups separately. Before each treatment from day 1 to day 10 and on day 11, 30, 60, the score of visual analogue scale (VAS) and skin lesion indexes were observed in the two groups. On day 60, the incidence of postherpetic neuralgia was recorded in the two groups. The levels of Th17 and Treg cells, Th17/Treg ratio in the peripheral blood, as well as serum levels of IL-10 and IL-17 were detected before and after treatment in the two groups. The clinical efficacy was compared between the two groups.@*RESULTS@#From day 6 to day 10 during treatment and on day 11, the scores of symptoms and physical signs in the combined therapy group were lower than those of the western medication group (P<0.05, P<0.01). On day 3, day 6 to day 10 during treatment and day 11, day 30, VAS scores in the combined therapy group were lower than those of the western medication group (P<0.05, P<0.01). On day 60, the incidence of postherpetic neuralgia in the combined therapy group was lower compared with that in the western medication group (P<0.05). The blister arresting time and scabbing time in the combined therapy group were shorter than those of the western medication group (P<0.05). After treatment, the level of Th17, and Th17/Treg ratio in the peripheral blood, as well as the serum levels of IL-10 and IL-17 were all lower in comparison with those in the western medication group (P<0.05). The curative and remarkably effective rate was 82.5% (33/40) in the combined therapy group, higher than 62.5% (25/40) in the western medication group (P<0.05).@*CONCLUSION@#The early application of fire needling combined with cupping therapy can effectively treat herpes zoster of acute stage, relieve pain, and reduce the incidence of postherpetic neuralgia, which may be related to reducing the levels of Th17 and Treg cells, and Th17/Treg ratio in the peripheral blood, as well as the serum levels of IL-10 and IL-17 so that the cellular immune balance is modulated.

Corynoxine B targets at HMGB1/2 to enhance autophagy for α-synuclein clearance in fly and rodent models of Parkinson's disease

Parkinson's disease (PD) is the most common neurodegenerative movement disease. It is featured by abnormal alpha-synuclein (α-syn) aggregation in dopaminergic neurons in the substantia nigra. Macroautophagy (autophagy) is an evolutionarily conserved cellular process for degradation of cellular contents, including protein aggregates, to maintain cellular homeostasis. Corynoxine B (Cory B), a natural alkaloid isolated from Uncaria rhynchophylla (Miq.) Jacks., has been reported to promote the clearance of α-syn in cell models by inducing autophagy. However, the molecular mechanism by which Cory B induces autophagy is not known, and the α-syn-lowering activity of Cory B has not been verified in animal models. Here, we report that Cory B enhanced the activity of Beclin 1/VPS34 complex and increased autophagy by promoting the interaction between Beclin 1 and HMGB1/2. Depletion of HMGB1/2 impaired Cory B-induced autophagy. We showed for the first time that, similar to HMGB1, HMGB2 is also required for autophagy and depletion of HMGB2 decreased autophagy levels and phosphatidylinositol 3-kinase III activity both under basal and stimulated conditions. By applying cellular thermal shift assay, surface plasmon resonance, and molecular docking, we confirmed that Cory B directly binds to HMGB1/2 near the C106 site. Furthermore, in vivo studies with a wild-type α-syn transgenic drosophila model of PD and an A53T α-syn transgenic mouse model of PD, Cory B enhanced autophagy, promoted α-syn clearance and improved behavioral abnormalities. Taken together, the results of this study reveal that Cory B enhances phosphatidylinositol 3-kinase III activity/autophagy by binding to HMGB1/2 and that this enhancement is neuroprotective against PD.