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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., (© 2022 The Authors. Molecular Ecology Resources published by John Wiley & Sons Ltd.)

Knowing the seasonality of COVID-19 helps decision-makers to take suitable interventions against the pandemic. In this study, we performed the Brown-Forsythe variance analysis on seasonal variations on different indicators based on the data on COVID-19 for the United States provided publicly by WHO. Our study finds that the seasonality of weekly cases and deaths of COVID-19 are strongly statistically supported by the data. The weekly total cases(/deaths) in winter are three to seven times(/two to three times) more than the other three single seasons. The ICU patients in winter and autumn are four to five times more than spring. The weekly hospital admissions in winter are four times more than spring. The mean of the positive rate in winter is five times more than spring. The findings of this research can be a reference in decision-making when taking interventions against the pandemic, such as taking stricter interventions in winter while considering less strict interventions in summer, etc., (© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Since the 21st century, art therapy has made great progress and development in China's education. To find out the relationship between art therapy and special children, hundreds of related literatures were analyzed using co-word analysis software, which shows that art therapy is increasingly important in special children and their education. Expressive art therapy has a good development prospect in college students' mental health education and group counseling. The connotation of group painting therapy is constantly enriched. The theme research of mandala painting therapy is closely related, and painting art therapy focuses on the psychological counseling research of different groups, but the two are still in the marginal position in the whole research, and have not been paid attention to. Therefore, in the future research, firstly, we should continue to strengthen the research of art therapy and expressive art therapy in special education and individual mental health education; second, further broaden the depth and breadth of group painting therapy; third, strengthen the study of mandala painting therapy and painting art therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cui and Wang.)

l-Arginine serves as a carbon and nitrogen source and is critical for Mycobacterium tuberculosis (Mtb) survival in the host. Generally, ArgR acts as a repressor regulating arginine biosynthesis by binding to the promoter of the argCJBDFGH gene cluster. In this study, we report that the dormancy regulator DosR is a novel arginine regulator binding to the promoter region of argC ( rv1652 ), which regulates arginine synthesis. Phosphorylation modification promoted DosR binding to a region upstream of the promoter. Cofactors, including arginine and metal ions, had an inhibitory effect on this association. Furthermore, DosR regulatory function relies on the interaction of the 167, 181, 182, and 197 amino acid residues with an inverse complementary sequence. Arginine also binds to DosR and directly affects its DNA-binding ability. Together, the results demonstrate that DosR acts as a novel transcriptional regulator of arginine synthesis in Mycobacterium bovis bacille Calmette-Guerin.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb). Mtb can overcome macrophage intracellular killing and lead to persistent infections. The proteases of Mtb are critical virulence factors that participate in immune responses. We determined that Rv3090 is a cell wall-associated protease and a potential pathogenic factor. To characterize the role of Rv3090 in Mtb, recombinant Msg_Rv3090 and Msg_pAIN strains were constructed to infect macrophages and mice. Lactate dehydrogenase assays and flow cytometry results showed that Rv3090 induces late macrophage apoptosis. In vivo infection experiments indicated that Rv3090 could induce hepatocyte and lung cell apoptosis and cause pathological damage to the spleen, livers and lungs. Msg_Rv3090 specifically stimulated the secretion of inflammatory cytokines including TNF-α, IL-6 and IL-1β. Overexpression of Rv3090 significantly promoted the survival of Msg in livers and lungs. Thus, Rv3090 protease triggered late cell apoptosis and contributed to the pathogenicity and dissemination of Mtb., Competing Interests: Declaration of competing interest The authors declare no conflicts of interests in regards to this manuscript., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Studies have shown that the main pathway for tick host localization and perception of mating information may be chemosensory. However, chemical communication in ticks is poorly understood, especially in those other than the Ixodes ticks. Niemann-Pick C2 (NPC2) protein and ionotropic receptors (IRs) are considered to be closely related to the perception of infochemicals in arthropods. Through bioinformatic analysis, eight NPC2 and four IR candidate genes were identified through screening and identification of the transcriptome sequencing database of Haemaphysalis longicornis. Phylogenetic tree analysis indicated that H. longicornis possesses similar homology to the genus Ixodes. A comparison of the expression of NPC2 and IR in tick forelegs (first pair of legs), hind legs (fourth pair of legs), and capitula using RT-PCR revealed that, barring HlonNPC2-8, 11 candidate genes were highly expressed in the foreleg and capitulum, which are the main sensory organs of ticks. They were also expressed in the hind legs, except for six genes that were not expressed in the males. RT-qPCR analysis showed upregulation and higher relative expression of HlonNPC2-1, HlonNPC2-3, HlonNPC2-6, and HlonNPC2-8 when stimulated by ammonium hydroxide, whereas the others were downregulated and demonstrated lower relative expression. These results further support the putative role of NPC2s as a new odorant carrier in ticks and present 12 promising candidate genes for understanding tick olfactory communication, enriching the data on these genes, especially outside the genus Ixodes., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Protein degradation occurs during the processing of dry-cured ham, which has important influences on the flavor and quality of products. The aim of this work was to study the degradation kinetics of myofibrillar proteins (MPs) and sarcoplasmic proteins (SPs) extracted from the biceps femoris muscle during the processing of Xuan'en ham. A relationship between protein degradation and the flavor formation was found. During the processing of Xuan'en ham, MPs and SPs were mainly degraded in the salting stage and incipient fermentation. Accompanied by protein degradation, the content of carbonyl group in SPs increased gradually, but in MPs, it first increased and then decreased. Interconversion between sulfhydryl and disulfide bonds was investigated during this processing. Oxidation, degradation, and thermal effects significantly affected the surface hydrophobicity of proteins. More than one hundred volatile compounds have been identified at each stage of ham preparation. Among them, organic acids were the predominant group, followed by hydrocarbons, aldehydes, alcohols, ketones, and esters., (© 2022 Institute of Food Technologists®.)

Background: Esophageal squamous cell carcinoma (ESCC) is characterized clinically by frequent recurrence, leading to a poor prognosis after radical surgery. The aim of this study was to identify a prognostic nomogram to predict the post-progression survival (PPS) of ESCC patients based on the features of primary tumor and recurrence., Methods: A total of 234 ESCC patients who underwent recurrence after radical surgery were enrolled in this study. The independent prognostic factors screened by the univariate and multivariate Cox regression analysis were subsequently used to construct a nomogram. The predictive performance of the nomogram was evaluated with the concordance index (C-index), decision curve, and the area under the receiver operating characteristic curve (AUC) and validated in two validation cohorts. The Kaplan-Meier curves of different recurrence patterns were analyzed., Results: The prognostic nomogram of PPS was established by integrating independent prognostic factors, including age, body mass index, number of lymph node dissection, recurrence pattern, and recurrence treatment. The nomogram demonstrated good performance, with C-index values of 0.756, 0.817, and 0.730 for the training and two validation cohorts. The 1-year AUC values were 0.773, 0.798, and 0.735 and 3-year AUC values were 0.832, 0.871, and 0.791, respectively. Furthermore, we found that patients with bone metastasis displayed the worst PPS compared to other isolated recurrence patterns., Conclusion: We constructed a nomogram to reliably predict PPS, which would be valuable to provide individual managements for ESCC patients after radical surgery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Leng, Cui, Chen, Wang, Yang, Wen, Fu and Liu.)

Background: In adolescents, multiple unhealthy behaviors frequently occur together and are likely to be associated with suicidal behaviors (SBs), increasing the risk of suicide. This study aimed to clarify the potential patterns of unhealthy behaviors in Chinese adolescents and to examine the associations between the different patterns of unhealthy behaviors and SBs., Methods: A total of 22,628 middle school students were enrolled in this study. Self-reported unhealthy behaviors and SBs were investigated using questionnaires. Latent class analysis (LCA) was performed based on five unhealthy behaviors [smoking, alcohol use (AU), diet pill use (DPU), screen time (ST), and problematic mobile phone use (PMPU)]. Multivariate logistic regressions were used to examine associations between the different patterns of unhealthy behaviors and SBs., Results: Four subgroups of unhealthy behaviors were identified by LCA, including high-risk class (smoking/AU/DPU/PMPU/ST), moderate-risk class 1 (DPU/PMPU), moderate-risk class 2 (smoking/AU/ST), and low-risk class. Compared with the low-risk class, moderate-risk class 1, moderate-risk class 2, and high-risk class had higher risks of suicidal ideation, suicide plan, and suicide attempt., Conclusions: These findings suggested that patterns of unhealthy behaviors were related to SBs in Chinese adolescents. Accordingly, considerations of different classes of unhealthy behaviors may be essential for developing effective preventive programs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Guo, Xue, Xia, Cui, Hu, Huang, Wan, Fang and Zhang.)

The long-term cultivation of tea plants without fertilization can severely decrease yield, but it remains unclear whether this soil nutrient deficiency affects tea quality. In this study, tea plants (Camellia sinensis (L.) Kuntze) cultivated in unfertilized soil for 11 years were analyzed. The soil nutrient deficiency down-regulated protochlorophyllide oxidoreductase-encoding gene expression, which adversely affected chlorophyll biosynthesis, ultimately leading to leaf etiolation. Because of decreased synthesis and increased degradation in response to nutrient deficiency, l-theanine content decreased to 11.4% of the control level, which increased the phenol-ammonia ratio and decreased taste quality. Soil nutrient deficiency also decreased the abundance of many aroma compounds (e.g., green leaf volatile, linalool and its oxides, and methyl salicylate). Thus, nutrient deficiency adversely influences tea color, taste, and aroma. This study provides researchers and tea growers with important information regarding the effects of soil nutrient deficiency on tea quality and the rational fertilization of tea gardens., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Cyclosporin A (CsA) induced nephrotoxicity i.e., renal fibrosis is a critical clinical problem in renal transplant patients, in which chronic inflammatory response is the major cause. Previously, we developed a nano-drug delivery system for carbon monoxide (CO), a multi-functional gaseous molecule with a potent anti-inflammatory effect, i.e., SMA/CORM2, which showed therapeutic potential in several inflammatory disease models. Accordingly, in this study, we explored the potential and usefulness of SMA/CORM2 on CsA induced renal fibrosis. When mice were exposed to CsA for 4 weeks, severe injuries in the kidney as revealed by decreased kidney function and histological examination, and activation of NLRP3 inflammasome, as well as renal fibrosis along with the upregulation of transforming growth factor β (TGFβ)/Smad signaling molecule were observed, whereas SMA/CORM2 (1 mg/kg) treatment remarkably ameliorated the inflammatory injury and fibrosis in the kidney. CO is the major effector molecule of SMA/CORM2 which significantly suppressed the activation of NLRP3 inflammasome, and induced the downregulation of TGFβ/Smad signaling. Inhibition of NLRP3 inflammasome by its inhibitor MCC950 also similarly decreased TGFβ/Smad expression and subsequently improved kidney injury and renal fibrosis, suggesting SMA/CORM2 induced suppression of TGFβ/Smad signaling and renal signaling via an NLRP3 inflammasome-dependent pathway. Compared to native CORM2, SMA/CORM2 exhibited better therapeutic/preventive effects owing to its superior water-solubility and bioavailability. These findings strongly indicated the applicability of SMA/CORM2 as an enhanced permeability and retention (EPR) effect-based nanomedicine for CsA induced renal fibrosis as well as other inflammatory diseases. STATEMENT OF SIGNIFICANCE: Carbon monoxide (CO) is an important gaseous signaling molecule that plays a crucial role in the maintenance of homeostasis. Because of its versatile functions, it exhibits the potential as the target molecule for many diseases, including inflammatory diseases and cancer. The development of stable and disease-targeted delivery systems of CO is thus of interest and importance. Previously we developed a nano micellar CO donor SMA/CORM2 which shows superior bioavailability and therapeutic potential in many inflammatory disease models. We reported here, SMA/CORM2, through controlled release of CO, greatly ameliorated CsA-induced renal fibrosis via suppressing the NLRP3 inflammasome mediated TGF-β/Smad pathway. These findings suggest a new anti-inflammatory mechanism of CO, which also provides a new approach for controlling CsA-induced nephrotoxicity., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022. Published by Elsevier Ltd.)

Insects have evolved numerous adaptations and colonized diverse terrestrial environments. Several polyneopterans, including dictyopterans (cockroaches and mantids) and locusts, have developed oothecae, but little is known about the molecular mechanism, physiological function, and evolutionary significance of ootheca formation. Here, we demonstrate that the cockroach asymmetric colleterial glands produce vitellogenins, proline-rich protein, and glycine-rich protein as major ootheca structural proteins (OSPs) that undergo sclerotization and melanization for ootheca formation through the cooperative protocatechuic acid pathway and dopachrome and dopaminechrome subpathway. Functionally, OSP sclerotization and melanization prevent eggs from losing water at warm and dry conditions, and thus effectively maintain embryo viability. Dictyopterans and locusts convergently evolved vitellogenins, apolipoprotein D, and laminins as OSPs, whereas within Dictyoptera, cockroaches and mantids independently developed glycine-rich protein and fibroins as OSPs. Highlighting the ecological-evolutionary importance, convergent ootheca formation represents a successful reproductive strategy in Polyneoptera that promoted the radiation and establishment of cockroaches, mantids, and locusts., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Introduction: Prostate cancer (PCa) is dependent on coupled androgen-androgen receptor (AR) signaling for growth and progression. Significant efforts have been made in this research field, as hormonal therapies have greatly improved the survival of patients with metastatic PCa (mPCa). The drug treatment agent JQ1, which potently abrogates bromodomain 4 (BRD4) localization to the AR target loci and therefore significantly impairs AR-mediated gene transcription, is a potent therapeutic option for patients with advanced PCa. In this study, we aimed to investigate the inhibitory effect of JQ1 combined with docetaxel on PCa cells in vitro for the first time. Furthermore, the 3D spheroid culture system was modeled to more accurately simulate the response of PCa cells to drugs. Methods: We established and measured 3D LNCaP spheroids in vitro in order to evaluate the susceptibility of 2D- and 3D-cultured LNCaP cells exposed to the same anti-cancer drug. Results: We demonstrated that JQ1 was an effective drug for promoting cell inhibition after docetaxel treatment in 2D- and 3D- cultured LNCaP cells. Inhibition of 3D cultured formation in the combined treatment group was significantly higher than that in docetaxel or JQ1 alone. Under the same conditions of drug solubility, the drug resistance of 3D spheroids was significantly higher than that of 2D cells. Moreover, d max and lg volume were suitable parameters for LNCaP cells/spheroid size displaying and evaluating cell viability. Conclusion: 3D cultured spheroids of PCa are an effective tool for studying PCa drug trials. JQ1 combined with docetaxel may be an effective treatment for advanced PCa. This combination therapy strategy deserves further evaluation in clinical trials., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xu, Pachnikova, Przybilla, Schäfer, Cui, Zhou, Chen, Zhao and Keilholz.)

Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible interstitial pulmonary disease due to chronic inflammatory responses. The prognosis of IPF is very poor, however, the therapeutic options are very limited. Previously we developed a polymeric micellar drug delivery system of carbon monoxide (CO) that is a pivotal anti-inflammatory gaseous molecule, i.e., SMA/CORM2, which exhibited therapeutic potentials against dextran sulfate sodium (DSS)-induced mouse colitis and acetaminophen (APAP) induced liver injury. Along this line, here we investigate the applicability of SMA/CORM2 on IPF using a bleomycin (BLM)-induced pulmonary fibrosis model. Severe inflammation and the consequent pulmonary fibrosis were triggered by BLM, whereas SMA/CORM2 treatment remarkably suppressed the inflammation progression and ameliorated the formation of fibrosis. CO is the effector molecule of SMA/CORM2, which exerted the therapeutic/protective effect mostly through suppressing the reprogramming of anti-inflammatory macrophages as revealed by the decreased expressions of CD206 and arginase-1 that were remarkably upregulated by BLM exposure. The suppression of macrophage polarization accompanied the downregulated hypoxia-inducible factor-1α (HIF-1α) and its target molecule heme oxygenase-1 (HO-1), suggesting a HIF-1α/HO-1 pathway for modulating macrophage reprogramming. As the downstream event of anti-inflammatory macrophage polarization, the alveolar epithelial to mesenchymal transition that is the major source of myofibroblast, the hallmark of IPF, was significantly suppressed by SMA/CORM2 via a TGF-β/Smad2/3 pathway. Compared to native CORM2 of equivalent dose, SMA/CROM2 exhibited a much better protective effect indicating its superior bioavailability as an enhanced permeability and retention (EPR) effect-based nanomedicine. We thus anticipate the application of SMA/CORM2 as a therapeutic candidate for IPF as well as other inflammatory diseases and disorders., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In this study, we aimed to elucidate the role of chronic cadmium (Cd) exposure in epithelial-mesenchymal transition (EMT) and thus malignant phenotypic changes of prostate cancer cells. Prostate cancer cells (PC-3 and DU145) were exposed to a non-toxic level (0.5 or 2 μM) of Cd for up to 3 months, which resulted in significantly promoted migration and invasion of the cells. These phenotypic changes were considered to be the consequence of enhanced EMT as evidenced by diminished expression of E-cadherin and increased vimentin expression. Regarding the mechanisms of Cd-induced EMT, we found Smad3 was activated but without upregulation of TGF-β. Alternatively, we found endoplasmic reticulum (ER) stress of prostate cancer cells was significantly evoked, which was parallel with the increased reactive oxygen species (ROS). Removal of ROS by N-acetylcysteine significantly reduced ER stress in prostate cancer cells, followed by the decrease of Smad3 phosphorylation and expression of nuclear Snail, resulting in the inhibition of EMT and malignant phenotypic changes of prostate cancer cells. These findings indicated a new TGF-β independent, ROS-mediated ER stress/Smad signaling pathway in chronic Cd exposure-induced EMT of prostate cancer cells, which could be a novel mechanism involved in cadmium-mediated cancer cells malignant transformation. Accordingly, ROS-induced ERs may become a novel preventive and therapeutic target for cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: Recent animal studies have demonstrated that the deletion of mouse double minute 2 (Mdm2) in mice leads to premature ovarian insufficiency (POI). The aim of the present study was to investigate whether mutations in the MDM2 gene contribute to POI in Chinese Han women., Methods: The coding region of the MDM2 gene was examined in 54 Chinese Han women with idiopathic POI and 54 Han healthy controls. Two known single nucleotide polymorphisms (SNPs), rs937283 in 5'-UTR and rs2870820 in intron 1, were compared between both POI and control groups., Results: There were no significant differences in the genotype distributions or allelic frequencies between the POI and control groups. No plausible causative mutations were identified., Conclusion: Our findings suggest that mutations in the coding region of the MDM2 gene may not represent a risk factor in the pathogenesis of idiopathic POI among Chinese Han women. Although we fail to confirm that MDM2 is a disease-causing gene, our study is the first to investigate the role of MDM2 in POI patients. Further studies with larger sample size from different ethnic populations are warranted., Competing Interests: None., (IJCEP Copyright © 2020.)

Background: The pro-oncogenic anterior gradient 2 (AGR2) is involved in tumor growth and drug resistance of breast cancer. Mechanisms that regulate expression of AGR2 still need to be elucidated., Methods: In this study, expression levels of AGR2 and miR-135b-5p were analyzed in different breast cancer cell lines as well as in clinical breast cancer tissues. The in vitro and in vivo functional effect of AGR2 and miR-135b-5p were also investigated. A luciferase reporter assay was applied to confirm the interaction between miR-135b-5p and AGR2 mRNA., Results: We identified AGR2 as a target of miR-135b-5p. Expression of AGR2 was up-regulated in doxorubicin-resistant breast cancer cells. AGR2 mediated doxorubicin-sensitivity of breast cancer cells both in vitro and in vivo. miR-135b-5p negatively regulated AGR2-expression of breast cancer cells increasing doxorubicin-sensitivity. However, miR-135b-5p was down-regulated in doxorubicin-resistant breast cancer cells as well as during treatment with doxorubicin, which might be a probable reason for over-expression of AGR2. Up-regulation of miR-135b-5p increased doxorubicin-sensitivity of breast cancer cells in vivo. In addition, levels of AGR2 negatively correlated with levels of miR-135b-5p in clinical breast cancer tissue samples., Conclusion: Our results highlight the potential of miR-135b-5p as a target for treating AGR2-expressing breast cancer with doxorubicin-resistance.

The discovery and creation of biocatalysts for plant biomass conversion are essential for industrial demand and scientific research of the plant cell wall. α-1,2 and α-1,3-L-arabinofuranosidases are debranching enzymes that catalyzing hydrolytic release of α-L-arabinofuranosyl residues in plant cell wall. Gene database analyses shows that GH62 family only contains specific α-L-arabinofuranosidases that play an important role in the degradation and structure of the plant cell wall. At present, there are only 22 enzymes in this group has been characterized. In this study, we cloned a novel α-1,3-arabinofuranosidase gene (poabf62a) belonging to glycoside hydrolase family 62 from Penicillium oxalicum sp. 68 and expressed it in Pichia pastoris. The molecular mass of recombinant PoAbf62A was estimated to be 32.9 kDa. Using p-nitrophenyl-α-l-arabinofuranoside (pNPαAbf) as substrate, purified PoAbf62A exhibited an optimal pH of 4.5 and temperature of 35 °C. Results of methylation and 13 C NMR analyses showed that PoAbf62A was exclusively α-1,3-arabinofuranosidase, specific for cleavage of α-1,3-arabinofuranosyl residues, and with the absence of activity towards α-1,2-arabinofuranose and α-1,5-arabinofuranose. Therefore, PoAbf62A exhibits high activity on sugar beet arabinan and wheat arabinoxylan, because their branched side chain are decorated with α-1,3-arabinofuranose. On the other hand, there is a lack of activity with linear-α-L-1,5-arabinan and xylan that only contained α-L-1,5-arabinofuranose or β-1,4-xylose. The α-1,3-arabinofuranosidase activity identified here provides a new biocatalytic tool to degrade hemicellulose and analyze the structure of plant cell walls.

The programmed death-1 (PD-1)/programmed death-ligands (PD-Ls) signal pathway has been implicated as a potential immune escape mechanism in several human cancers. However, the studies of PD‑1/PD‑Ls pathway in esophageal squamous cell carcinoma (ECSS) are not yet sufficient. The current study investigated the expression of PD‑L1, PD‑L2 and PD‑1 in ESCC tissues. The correlations between the expression of these proteins and clinical histopathological parameters were analyzed. Then the stable transfected Ec109 cell lines overexpressing PD‑L1/PD‑L2 were established by plasmid transfection successfully. Ec109 and CD8+ T cells were co‑cultured to analyze the effects of PD‑1/PD‑Ls signal pathway on the function of CD8+ T cells including proliferation, apoptosis and interferon‑γ production. We found that PD‑L1-positive patients had significantly poorer prognosis than the negative patients, while their prognosis was not related to PD‑L2 expression. The count of PD‑1+ TILs (tumor‑infiltrating lymphocytes) was negatively correlated with both PD‑L1 and PD‑L2 expression. In functional studies, we found that PD‑1/PD‑Ls signal pathway was able to downregulate the function of CD8+ T lymphocyte and its function could be restored by blocking the signal pathway. This indicates that PD‑1/PD‑Ls may prevent effective antitumor immunity, which provides important evidence to delineate the cellular immune deficiency mechanism in ESCC. Therefore, PD-1/PD-Ls are predicted to become novel targets for ESCC immunotherapy.

Cyclooxygenase-2 (COX-2) and interleukin-32 (IL-32) expression has been examined in various carcinomas and inflammations, and has been suggested to be significant in tumor progression and prognosis. The present study was conducted to investigate the expression of COX-2 and IL-32 in primary gastric B-cell lymphoma in order to define their clinical significance and their association with Helicobacter pylori (Hp) infection. COX-2 and IL-32 protein expression was detected in 31 primary gastric B-cell lymphoma patients and 19 chronic gastritis patients with immunohistochemistry. COX-2 and IL-32 expression was significantly higher in primary gastric lymphoma (PGL) tissues compared with gastritis tissues (51.6 vs. 21.1% for COX-2, P=0.032; and 58.1 vs. 26.3% for IL-32, P=0.029) and was significantly higher in Hp + lymphoma tissues compared with Hp - lymphoma tissues (66.7 vs. 20% for COX-2, P=0.015; and 71.4 vs. 30% for IL-32, P=0.029). In the PGL tissues, the expression level of COX-2 was positively correlated with the expression level of IL-32, and the two were each positively correlated with Hp infection (P=0.004 for COX-2 and IL-32; P=0.01 for COX-2 and Hp infection; and P=0.003 for IL-32 and Hp infection). COX-2 expression was found to be significantly associated (P<0.05) with an aggressive tumor type, higher expression of Ki-67, frequent lymph node metastasis and advanced stage. IL-32 expression was found to be significantly correlated (P<0.05) with frequent lymph node metastasis and an advanced stage. The survival time was longer in the COX-2 - and IL-32 - lymphoma patients compared with the COX-2 + and IL-32 + lymphoma patients, but these differences were not statistically significant. These results suggested that Hp infection and the expression of COX-2 and IL-32 were closely linked with each other, and that the overexpression of COX-2 and IL-32 was correlated with tumor progression in primary gastric B-cell lymphoma, thus indicating potential novel therapeutic target.

Evaluation of bone marrow involvement (BMI) by conventional bone marrow biopsy (BMB) can generate false-negative results if marrow disease is focal. The sensitivity of 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) in assessing BMI in extranodal NK/T cell lymphoma (ENKL) has not been determined. We retrospectively collected clinical data from a series of 55 patients with newly diagnosed ENKL, who have received both FDG-PET/CT and BMB prior to treatment. BMB results were used as reference standard. Twelve patients (21.8 %) were considered positive lymphomatous infiltration by FDG-PET/CT (PET-CT/BM+), and five patients (9 %) were identified positive by BMB (BMB/BM+). There was a discordant result in seven patients who were PET-CT/BM+ but BMB/BM-. The sensitivity and specificity of FDG-PET/CT for identifying BMI were 100 and 86 %, respectively. Then, we analyzed the overall survival (OS) and progression-free survival (PFS) of patients who were PET-CT/BM+ and PET-CT/BM-. The median follow-up time was 16 months (range, 3 to 43 months). PET-CT/BM+ patients possessed worse 2-year OS than PET-CT/BM- patients (84.8 vs 67.9 %, P < 0.05). The estimated 2-year PFS for PET-CT/BM- and PET-CT/BM+ patients were 72.7 and 41.9 % (P < 0.05), respectively. However, it was hard to conclude that patients who were PET-CT/BM+ had similar survivals to advanced-stage patients due to the low number of patients who were PET-CT/BM+. In conclusion, FDG-PET/CT can complementally detect positive BMI patients missed by BMB in ENKL. The utility of FDG-PET/CT for defining bone marrow status has important prognostic value.

Rv2525c from Mycobacterium tuberculosis belongs to the domain of unknown function (DUF) 1906 superfamily, but it also contains the motif G-X-S-X-G, the consensus active site sequence of the ester/lipid family. Biochemical analysis indicated that the mature Rv2525c protein is secreted. The discovery and characterisation of novel enzymes secreted by M. tuberculosis are vital for understanding the pathogenesis of the most important human bacterial pathogen. The proteome of M. tuberculosis contains over 400 potentially secreted proteins, of which the majority remain uncharacterised. In this study, we cloned and expressed the rv2525c gene in Escherichia coli and purified the recombinant protein using a three-step process (affinity chromatography, ion exchange chromatography, gel filtration chromatography), obtaining more than 99% pure protein. Mass spectrometry was performed to confirm that the purified protein was Rv2525c. Circular dichroism spectroscopy results showed that its conformation was stable at pH ranging from 6.0 to 8.0 and at temperatures ≤ 40 °C. Moreover, we tested the esterase activity using p-nitrophenyl esters (C2, C4, C6, C8, C12, C14, C16). This enzyme exhibited broad substrate acceptance, preferentially hydrolysing p-nitrophenyl butyrate (C4) at pH 7.0 and 37 °C. The dynamic activity test demonstrated that the optimal conditions were pH 8.0 and 38 °C. Site-directed mutagenesis studies revealed that Gly 113, Ser 115 and Gly 117 residues play catalytic roles in Rv2525c.

To develop new anticancer agents, we prepared a sulfated polysaccharide (SCGLP1) from the fruiting bodies of Ganoderma lucidum, and the effect of SCGLP1 on human osteosarcoma MG63 cell line was investigated. Our result showed that treatment with SCGLP1 resulted in a significant inhibitory effect on cell proliferation and cell viability of MG63 cells in a dose- and time-dependent manner and caused apoptotic death in MG63 cells through an increase in G0/G1 phase arrest, but had minor cytotoxic effect on human normal osteoblast (NHOst) cells. Western blot analysis identified that SCGLP1-induced apoptosis was associated with an increased protein expression of proapoptotic Bax and Bad, decreased expression of antiapoptotic Bcl-2 and Bcl-XL, loss of mitochondrial membrane potential (Δψm), the release of mitochondrial cytochrome c to cytosol, and cleavage of caspase-9, caspase-3, and poly(ADP-ribose) polymerase (PARP). In addition, pretreatment with the pan-caspase inhibitor (z-VAD-fmk) blocked the SCGLP1-induced apoptosis in MG63 cells. The data indicate that SCGLP1-induced apoptosis is primarily associated with caspase-3- and caspase-9-dependent apoptotic pathway.

The silent Twist gene may increase the sensitivity of cervical cancer cells chemotherapy to paclitaxel, thus was a new idea to improve the efficacy of cancer chemotherapy. The aim was to explore chemotherapy sensitivity of silent Twist gene increased cervical cancer cells to paclitaxel through study the proliferation and apoptosis of cervical cancer Twist gene after paclitaxel treatment. Cervical carcinoma Caski cells and Hela cells was cultured in vitro, mRNA gene expression was detected by using semi-quantitative, fluorescence quantitative PCR, and transferred to Caski cells transiently, and affected with paclitaxel solution of five kinds of different concentrations of 0.001, 0.01, 0.1, 1, 10 umol/L respectively. Then the results of <0.05). Every 12h after 36 h, the expression inhibition rate in two groups of Caski cells that has transfected this study was Twist gene expression in Caski cells was higher than in Hela cells, which was of significant difference (p siRNA1 and siRNA2 were 20.3%, 38.2%, 33%, 24%, 68.6%, 50.8% respectively. After 48 h in five different concentrations of paclitaxel effect, the cell growth inhibition rate of group siRNA2 with the best transfection efficiency was obviously higher than that of negative control group and blank control group, and the growth inhibition rates showed concentration dependence (p<0.05). It can be concluded that Twist gene in Caski cell was of high expression and the silent Twist gene could inhibit Caski cell proliferation and promote its apoptosis, thus to improve the chemotherapy sensitivity of Caski cells.