Association Between Polymorphisms in DNA Damage Repair Pathway Genes and Female Breast Cancer Risk.

Breast cancer risk have been discussed to be associated with polymorphisms in genes as well as abnormal DNA damage repair function. This study aims to assess the relationship between genes single nucleotide polymorphisms (SNPs) related to DNA damage repair and female breast cancer risk in Chinese population. A case-control study containing 400 patients and 400 healthy controls was conducted. Genotype was identified using the sequence MassARRAY method and expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2) in tumor tissues was analyzed by immunohistochemistry assay. The results revealed that ATR rs13091637 decreased breast cancer risk influenced by ER, PR (CT/TT vs. CC: adjusted odds ratio [OR] = 1.54, 95% confidence interval [CI]: 1.04-2.27, p = 0.032; CT/TT vs. CC: adjusted OR = 1.63, 95%CI: 1.14-2.35, p = 0.008) expression. Stratified analysis revealed that PALB2 rs16940342 increased breast cancer risk in response to menstrual status (AG/GG vs. AA: adjusted OR = 1.72, 95%CI: 1.13-2.62, p = 0.011) and age of menarche (AG/GG vs. AA: adjusted OR = 1.54, 95%CI: 1.03-2.31, p = 0.037), whereas ATM rs611646 and Ku70 rs132793 were associated with reduced breast cancer risk influenced by menarche (GA/AA vs. GG: adjusted OR = 0.50, 95%CI: 0.30-0.95, p = 0.033). In a summary, PALB2 rs16940342, ATR rs13091637, ATM rs611646, and Ku70 rs132793 were associated with breast cancer risk.

Efficacy and safety of a combination treatment of immune checkpoint inhibitors in metastatic breast cancer: a systematic review and meta-analysis.

PURPOSE: Immune checkpoint inhibitors (ICIs) in combination with chemotherapy have showed its benefits in clinical studies, and here we conducted a further evaluation on the safety and efficacy of this treatment strategy. METHODS: A systematic literature review was conducted in PubMed, Embase and Cochrane Library to identify clinical studies on ICIs and chemotherapy for metastatic breast cancer. The primary efficacy endpoints were progression-free survival (PFS) and overall survival (OS), and adverse events (AEs) were analyzed. Random or fixed effects models were used to estimate pooled Hazard ratio (HR), odds ratio (OR) and the data of 95% confidence interval (CI) depend on the Heterogeneity. Cochrane risk assessment tool was used to assess risk of bias. We also drew forest plots and funnel plots, respectively. RESULTS: Seven studies with intend-to-treat (ITT) population for 3255 patients were analyzed. ICIs pooled therapy showed clinical benefits compared with chemotherapy alone, improving PFS (HR = 0.81, 95% CI: 0.74-0.90) of patients with metastatic triple negative breast cancer (mTNBC), especially in patients with PD-L1-positive tumors. However, it had no effect on OS (HR = 0.92, 95% CI 0.85-1.01). Besides, mTNBC patients received pooled therapy were less frequently to have AEs (OR = 1.30, 95% CI: 1.09-1.54). In patients with metastatic Human Epidermal Growth Factor Receptor 2 (HER2) negative breast cancer, pooled therapy showed no benefit for PFS (HR = 0.80, 95% CI: 0.50-1.28) and OS (HR = 0.87, 95% CI: 0.48-1.58). CONCLUSION: Pooled therapy had improved PFS in mTNBC patients, especially in patients with PD-L1-positive tumors, and it was less likely to cause grade ≥ 3 AEs.

Schwann cell-derived extracellular vesicles promote memory impairment associated with chronic neuropathic pain.

BACKGROUND: The pathogenesis of memory impairment, a common complication of chronic neuropathic pain (CNP), has not been fully elucidated. Schwann cell (SC)-derived extracellular vesicles (EVs) contribute to remote organ injury. Here, we showed that SC-EVs may mediate pathological communication between SCs and hippocampal neurons in the context of CNP. METHODS: We used an adeno-associated virus harboring the SC-specific promoter Mpz and expressing the CD63-GFP gene to track SC-EVs transport. microRNA (miRNA) expression profiles of EVs and gain-of-function and loss-of-function regulatory experiments revealed that miR-142-5p was the main cargo of SC-EVs. Next, luciferase reporter gene and phenotyping experiments confirmed the direct targets of miR-142-5p. RESULTS: The contents and granule sizes of plasma EVs were significantly greater in rats with chronic sciatic nerve constriction injury (CCI)than in sham rats. Administration of the EV biogenesis inhibitor GW4869 ameliorated memory impairment in CCI rats and reversed CCI-associated dendritic spine damage. Notably, during CCI stress, SC-EVs could be transferred into the brain through the circulation and accumulate in the hippocampal CA1-CA3 regions. miR-142-5p was the main cargo wrapped in SC-EVs and mediated the development of CCI-associated memory impairment. Furthermore, α-actinin-4 (ACTN4), ELAV-like protein 4 (ELAVL4) and ubiquitin-specific peptidase 9 X-linked (USP9X) were demonstrated to be important downstream target genes for miR-142-5p-mediated regulation of dendritic spine damage in hippocampal neurons from CCI rats. CONCLUSION: Together, these findings suggest that SCs-EVs and/or their cargo miR-142-5p may be potential therapeutic targets for memory impairment associated with CNP.

Skin-Friendly Flexible Ultraviolet Detectors Based on Reversibly Deformable Worm-Like Polymer Nanoparticles.

Flexible ultraviolet (UV) light detection technology has important applications in wearable devices, smart sensors, and other fields and attracts much attention in recent years. However, for most semiconductor-based UV detectors, the elastic modulus between rigid semiconductors and flexible substrates is mismatched, which makes it difficult to fabricate UV detectors that meet the needs of wearable devices. Herein, a fully flexible, large-scale, skin-friendly UV photodetector component centered on photo-responsive worm-like polymer nanoparticles (NPs) is developed, and the resulting device can quantitatively detect UV illumination. Skin-friendly poly(vinyl alcohol) (PVA), amphiphilic azobenzene-containing polymer NPs (AzNPs), and water-soluble ionic liquids (IL) are formed into (AzNPs-IL)/PVA fabrics by electrospinning. There are interactions such as hydrogen bonding among PVA, AzNPs, and IL, which make the material system stable. The UV detector made of the fabric realizes UV sensing through the illuminance-mechanical stress-electrical signal conversion mechanism. It is capable of achieving a response time of 9 s, a detection range of 10-150 mW cm-2 , and stability for 1000 cycle tests upon 365 nm UV irradiation. Moreover, it has good skin affinity, and the water contact angle of the fabric is only 23.57°, which holds great promise for wearable smart devices.

Blue Light Attracts More Spodoptera frugiperda Moths and Promotes Their Flight Speed.

Light traps are a useful method for monitoring and controlling the important migratory pest, the fall armyworm, Spodoptera frugiperda. Studies have shown that S. frugiperda is sensitive to blue, green, or ultraviolet (UV) light, but the conclusions are inconsistent. Furthermore, conventional black light traps are less effective for trapping S. frugiperda. To improve the trapping efficiency of this pest, it is crucial to determine the specific wavelength to which S. frugiperda is sensitive and measure its flight capability under that wavelength. This study investigated the effects of light wavelength on the phototaxis and flight performance of S. frugiperda. The results showed that blue light was the most sensitive wavelength among the three different LED lights and was unaffected by gender. The flight capability of S. frugiperda varied significantly in different light conditions, especially for flight speed. The fastest flight speed was observed in blue light, whereas the slowest was observed in UV light compared to dark conditions. During a 12 h flight period, speed declined more rapidly in blue light and more slowly in UV, whereas speed remained stable in dark conditions. Meanwhile, the proportion of fast-flying individuals was highest under blue light, which was significantly higher than under UV light. Therefore, the use of light traps equipped with blue LED lights can improve the trapping efficiency of S. frugiperda. These results also provide insights for further research on the effects of light pollution on migratory insects.

Hsa_circ_0007990 promotes breast cancer growth via inhibiting YBX1 protein degradation to activate E2F1 transcription.

Breast cancer (BC) is the most commonly diagnosed malignant tumour in females worldwide. Although remarkable advances in early detection and treatment strategies have led to decreased mortality, recurrence and metastasis remain the major causes of cancer death in BC patients. Increasing evidence has demonstrated that circular RNAs (circRNAs) play critical roles in cancer progression. However, the detailed biological functions and molecular mechanisms of circRNAs in BC are unclear. The aim of this study was to investigate the possible role of circRNAs in the progression of BC. Differentially expressed circRNAs in BC were identified by integrating breast tumour-associated somatic CNV data and circRNA high-throughput sequencing. Aberrant hsa_circ_0007990 expression and host gene copy number were detected in BC cell lines via quantitative polymerase chain reaction (qPCR). The expression level of hsa_circ_0007990 in BC tissues was validated by in situ hybridization (ISH). Loss- and gain-of-function experiments were performed in vitro and in vivo, respectively, to explore the potential biological function of hsa_circ_0007990 in BC. The underlying mechanisms of hsa_circ_0007990 were investigated through MS2 RNA pull-down, RNA immunoprecipitation, RNA fluorescence in situ hybridization, immunofluorescence, chromatin immunoprecipitation and luciferase reporter assays. The levels of hsa_circ_0007990 were elevated in BC tissues and cell lines, an effect that was partly due to host gene copy number gains. Functional assays showed that hsa_circ_0007990 promoted BC cell growth. Mechanistically, hsa_circ_0007990 could bind to YBX1 and inhibit its degradation by preventing ubiquitin/proteasome-dependent degradation, thus enhancing the expression of the cell cycle-associated gene E2F1. Rescue experiments suggested that hsa_circ_0007990 promoted BC progression through YBX1. In general, our study demonstrated that hsa_circ_0007990 modulates the ubiquitination and degradation of YBX1 protein and further regulates E2F1 expression to promote BC progression. We explored the possible function and molecular mechanism of hsa_circ_0007990 in BC and identified a novel candidate target for the treatment of BC.

Phenotype and genotype analysis for Helicobacter pylori antibiotic resistance in outpatients: a retrospective study.

To investigate the antibiotic resistance of Helicobacter pylori (H. pylori) in outpatients and to explore the consistency between genotype and phenotype of H. pylori antibiotic resistance. A retrospective study on outpatients screened with urea breath test for H. pylori infection in Nanjing First Hospital from April 2018 to January 2022. Patients who tested positive underwent a consented upper endoscopy, and the H. pylori infection was confirmed by rapid urease test (RUT) and H. pylori culture. For antibiotic resistance phenotype analysis, the H. pylori strains isolated from gastric biopsy were tested for antibiotic resistance phenotype by the Kirby-Bauer disk diffusion test. In addition, the antibiotic resistance genotype of isolated H. pylori was tested with a real-time polymerase chain reaction. A total of 4,399 patients underwent H. pylori infection screening, and 3,306 H. pylori strains were isolated. The antibiotic resistance phenotype test revealed that the resistance rates of metronidazole (MTZ), clarithromycin (CLR), levofloxacin (LEV), amoxicillin (AMX), furazolidone (FR), and tetracycline (TE) were 74.58%, 48.61%, 34.83%, 0.76%, 0.27%, and 0.09%, respectively. Additionally, the antibiotic resistance genotype test revealed that rdxA gene mutation A610G (92.96%), A91G (92.95%), C92A (93.00%), and G392A (95.07%) were predominant in H. pylori with MTZ resistance; 23S rRNA gene mutation A2143G (86.47%) occurred in most H. pylori with CLR resistance; and gyrA gene mutation 87Ile/Lys/Tyr/Arg (97.32%) and 91Asn/Gly/Tyr (90.61%) were the most popular mutations in strains with LEV resistance. The phenotypic resistance and genotypic resistance to CLR (kappa value = 0.824) and LEV (kappa value = 0.895) were in good agreement. The history of eradication with MTZ, CLR, LEV, and AMX was correlated with H. pylori resistance. In short, this study demonstrated that drug resistance of H. pylori was mainly to MTZ, CLR, and LEV in local outpatients. Three drugs can be selected for increased MICs (Minimum Inhibitory Concentration) via single chromosomal mutations. In addition, the genotype could be used to predict the phenotypic H. pylori resistance to CLR and LEV. IMPORTANCE Helicobacter pylori is a key bacterium that causes stomach diseases. There was a high prevalence of H. pylori in the Chinese population. We analyzed the resistance phenotype and genotype characteristics of H. pylori in 4,399 outpatients at the First Hospital of Nanjing, China. We found a higher resistance rate to metronidazole (MTZ) , clarithromycin (CLR), and levofloxacin (LEV), and the genotype could be used to predict the phenotypic H. pylori resistance to CLR and LEV. This study provides information on H. pylori infection and also provides guidance for clinical doctors' drug treatment.

Antennal transcriptome analysis of odorant-binding proteins and characterization of GOBP2 in the variegated cutworm Peridroma saucia.

Odorant-binding proteins (OBPs) are expressed at extremely high concentrations in the chemo-sensilla lymph of insects and have long been thought to be crucial for delivering the semiochemicals to the odorant receptors. They are represented by multiple classes: general odorant-binding proteins (GOBP1 and GOBP2) and pheromone-binding proteins. In the current study, we identified a total of 35 OBPs in the antennal transcriptome of Peridroma saucia, a worldwide pest that causes serious damage to various crops. A gene expression value (TPM, transcripts per million) analysis revealed that seven OBPs (PsauPBP1/2/3, PsauGOBP1/2, PsauOBP6, and PsauOBP8) were highly abundant in the antennae. Next, we focused on the expression and functional characterization of PsauGOBP2. Real-time quantitative-PCR analysis demonstrated that PsauGOBP2 was predominantly expressed in the antennae of both sexes. Fluorescence binding assays showed that the recombinant PsauGOBP2 strongly binds to the female sex pheromone components Z11-16: Ac (Ki = 4.2 µM) and Z9-14: Ac (Ki = 4.9 µM) and binds moderately (6 µM ≤ Ki ≤ 13 µM) to the host plant volatiles phenylethyl acetate, ß-myrcene, and dodecanol. Further 3D structural modeling and molecular docking revealed that several crucial amino acid residues are involved in ligand binding. The results not only increase our understanding of the olfactory system of P. saucia but also provide insights into the function of PsauGOBP2 that has implications for developing sustainable approaches for P. saucia management.

Azobenzene-Containing Liquid Crystalline Twisted Ribbons via Polymerization-Induced Hierarchical Self-Assembly.

Polymerization-induced self-assembly incorporating liquid crystallization, as a polymerization-induced hierarchical self-assembly (PIHSA) method to produce polymeric particles with anisotropic morphologies facilely and efficiently, has drawn wide attention recently. However, the means of regulating the morphologies of liquid crystalline (LC) polymer assemblies still need to be explored. Herein, a route is presented to fabricate the twisted ribbons via PIHSA containing azobenzene based on poor reversible addition-fragmentation chain transfer (RAFT) control, called poorly controlled PIHSA. Cyano-4-(dodecylsulfanylthiocarbonyl)sulfanyl pentanoic acid-2-(2-pyridyldithio) ethyl ester is used as the RAFT agent with poor controllability, and the morphological evolution from ribbons to twisted ribbons can be observed in the corresponding PIHSA system. The formation mechanism of the twisted ribbons is studied systematically and the broad molecular weight distribution is considered to be the decisive factor. Moreover, the supramolecular chirality induced by symmetry breaking is also related to the twist of the ribbons. This study enriches the methods of controlling the morphologies of LC polymer particles and is helpful for further clarifying the mechanism of PIHSA.

Expression, affinity, and binding mode analysis of antennal-binding protein X in the variegated cutworm Peridroma saucia (Hübner).

The variegated cutworm Peridroma saucia (Hübner) is a worldwide pest that causes serious damage to many crops. Odorant-binding proteins (OBPs) are small soluble proteins involved in the first step of odorant reception. In moths, antennal-binding protein Xs (ABPXs) represent a main subfamily of classic OBPs. However, their functions remain unclear. Here, we cloned the ABPX gene from the antennae of P. saucia. RT-qPCR and western-blot analyses showed that PsauABPX is antenna-predominant and male-biased. Further temporal expression investigation indicated that the expression of PsauABPX started 1 day before eclosion and reached the highest 3 days after eclosion. Next, fluorescence binding assays revealed that recombinant PsauABPX had high binding affinities with P. saucia female sex pheromone components Z11-16: Ac and Z9-14: Ac. Then, molecular docking, molecular dynamics simulation, and site-directed mutagenesis were employed to identify key amino acid residues involved in the binding of PsauABPX to Z11-16: Ac and Z9-14: Ac. The results demonstrated that Val-32, Gln-107 and Tyr-114 are essential for the binding to both sex pheromones. This study not only give us insight into the function and binding mechanism of ABPXs in moths, but could also be used to explore novel strategies to control P. saucia.

Light-Triggered Reversible Swelling of Polymeric Spheres via Surfactant-Free RAFT Emulsion Polymerization-Induced Self-Assembly.

Responsive photonic crystals (RPCs) assembled by monodisperse colloidal particles have attracted enormous interest recently due to their tremendous applications in smart devices. Their structural colors can be determined by particle sizes. However, the lack of a reliable way to tune the sizes in situ limits their development. Herein, we present an efficient route to solve this problem through the fabrication of spherical polymeric particles with light-triggered reversible swelling behavior via surfactant-free reversible addition-fragmentation chain transfer (RAFT) emulsion polymerization-induced self-assembly (PISA). Amphiphilic macro-RAFT agents containing azobenzene groups were synthesized and subsequently employed to mediate the polymerization of methyl methacrylate. Uniform submicron spheres were obtained by modulating solid contents and other parameters. Benefiting from the photoisomerization of azobenzene moieties, the particle sizes expanded and contracted upon alternative ultraviolet/visible-light irradiation accordingly. This strategy will be a supplement to the emulsion PISA and especially give aid to the progress of the RPC materials.

The prognostic values of FOXP3+ tumor-infiltrating T cells in breast cancer: a systematic review and meta-analysis.

BACKGROUND: Tumor microenvironment is infiltrated by many immune cells, of which Regulatory T (Treg) cells are usually considered as negative regulators of the immune responses. However, the effect of FOXP3+ (forkhead box transcription factor 3) Treg cells infiltrated into the tumor areas on the prognosis of breast cancer is controversial. This meta-analysis aimed to dissect the potential values of FOXP3+ tumor-infiltrating lymphocytes (TILs) as a prognosis predictor of breast cancer. METHODS: After systematic retrieval of all relevant studies, 28 eligible articles were identified for meta-analysis. Odd ratio (OR), hazard ratio (HR), and 95% confidence interval (CI) were obtained for pooled analyses of pathological complete response (pCR), overall survival (OS), and corresponding forest plots and funnel plots were plotted, respectively. RESULTS: Pooled results revealed that patients with higher levels of FOXP3+ TILs experienced better pCR (OR: 1.24, 95% CI 1.09-1.41) and OS (HR: 0.79, 95% CI 0.64-0.97). Subgroup analysis revealed that elevated FOXP3+ TILs were significantly associated with improved pCR (OR: 1.20, 95% CI 1.02-1.40) and OS (HR: 0.22, 95% CI 0.06-0.88) in human epidermal growth factor receptor 2 positive (HER2+) breast cancer patients. Furthermore, FOXP3+ TILs in the stromal area were statistically correlated with the favorable pCR (OR: 1.22, 95% CI 1.08-1.38) and OS (HR: 0.68, 95% CI 0.49-0.96). CONCLUSIONS: The predictive role of FOXP3+ TILs in the prognosis of breast cancer is influenced by various factors such as molecular subtype of breast cancer and the location of Treg. In HER2+ breast cancer and triple-negative breast cancer, FOXP3+ TILs are associated with better pCR and OS. Additionally, FOXP3+ TILs in stromal represent a favourable prognosis.

Trifluoro-icaritin ameliorates spared nerve injury-induced neuropathic pain by inhibiting microglial activation through α7nAChR-mediated blockade of BDNF/TrkB/KCC2 signaling in the spinal cord of rats.

Neuropathic pain is still a serious and unsolved health problem. Activation of α7 nicotinic acetylcholine receptor (α7nAChR) is known to modulate neuropathic pain by inhibiting microglial activation and BDNF/TrkB/KCC2 signaling. We previously identified that trifluoro-icaritin (ICTF) has an attenuated effect on spared nerve injury (SNI)-induced neuropathic pain, but its potential mechanisms remain unknown. Here, the pain-related behaviors were determined by paw withdrawal threshold (PWT), CatWalk gait analysis, rotarod test, open field test and elevated plus maze test. The expression of pain-related signal molecules was evaluated by Western blot and immunofluorescence staining. The results showed that ICTF (5.0 mg/kg, i.p.) successfully relieved SNI-induced mechanical allodynia and anxiety-like behavior, we subsequently found there existed either positive or negative correlation between mechanical allodynia and gait parameters or rotating speed following ICTF treatment. Moreover, ICTF not only enhanced the expression of spinal α7nAChR, KCC2, CD206 and IL-10, but also decreased the levels of spinal BDNF, TrkB, CD11b, Iba-1, CD40 and IL-1ß in SNI rats. Conversely, α7nAChR antagonist α-Bgtx (I.T.) effectively reversed the inhibitory effects of ICTF on SNI rats, resulting in a remarkable improvement of mechanical allodynia, activation of microglia. and suppression of α7nAChR-mediated BDNF/TrkB/KCC2 signaling. Additionally, exogenous BDNF (I.T.) dramatically abrogated both blockade of BDNF/TrkB/KCC2 cascade and alleviation of mechanical allodynia by ICTF treatment. Altogether, the study highlighted that ICTF could relieve SNI-induced neuropathic pain by suppressing microglial activation via α7nAChR-mediated inhibition of BDNF/TrkB/KCC2 signaling in the spinal cord, suggesting that ICTF may be served as a possible painkiller against neuropathic pain.

Sex pheromone communication in an insect parasitoid, Campoletis chlorideae Uchida.

Sex pheromones are pivotal for insect reproduction. However, the mechanism of sex pheromone communication remains enigmatic in hymenopteran parasitoids. Here we have identified the sex pheromone and elucidated the olfactory basis of sex pheromone communication in Campoletis chlorideae (Ichneumonidae), a solitary larval endoparasitoid of over 30 lepidopteran pests. Using coupled gas chromatography-electroantennogram detection, we identified two female-derived pheromone components, tetradecanal (14:Ald) and 2-heptadecanone (2-Hep) (1:4.6), eliciting strong antennal responses from males but weak responses from females. We observed that males but not females were attracted to both single components and the blend. The hexane-washed female cadavers failed to arouse males, and replenishing 14:Ald and 2-Hep could partially restore the sexual attraction of males. We further expressed six C. chlorideae male-biased odorant receptors in Drosophila T1 neurons and found that CchlOR18 and CchlOR47 were selectively tuned to 14:Ald and 2-Hep, respectively. To verify the biological significance of this data, we knocked down CchlOR18 and CchlOR47 individually or together in vivo and show that the attraction of C. chlorideae to their respective ligands was abolished. Moreover, the parasitoids defective in either of the receptors were less likely to court and copulate. Finally, we show that the sex pheromone and (Z)-jasmone, a potent female attractant, can synergistically affect behaviors of virgin males and virgin females and ultimately increase the parasitic efficiency of C. chlorideae. Our study provides new insights into the molecular mechanism of sex pheromone communication in C. chlorideae that may permit manipulation of parasitoid behavior for pest control.

Ultrastructure of Ejaculatory Ducts of Cerapanorpa nanwutaina and Furcatopanorpa longihypovalva (Mecoptera: Panorpidae).

The ultrastructure of the ejaculatory duct was investigated in the scorpionflies Cerapanorpa nanwutaina (Chou 1981) and Furcatopanorpa longihypovalva (Hua & Cai, 2009) (Mecoptera: Panorpidae) using light and transmission electron microscopy. The ejaculatory ducts of both species comprise a median duct and an accessory sac. The median duct consists of a basal lamina, a mono-layered epithelium, a subcuticular cavity, and an inner cuticle. The accessory sac contains a single layer of epithelium and a basal lamina. A muscular layer is present in the accessory sac of C. nanwutaina and in the median duct of F. longihypovalva. The epithelia in the median duct and the accessory sac are well developed, their cells containing numerous cisterns of rough endoplasmic reticulum, mitochondria, and microvilli. The secretions of the median duct are first extruded into the subcuticular cavity and then into the lumen through an inner cuticle, while the secretions of the accessory sac are discharged directly into the lumen. The ejaculatory duct of F. longihypovalva is longer and has thicker epithelium with more cell organelles and secretions than that of C. nanwutaina.

Candidate chemosensory receptors in the antennae and maxillae of Spodoptera frugiperda (J. E. Smith) larvae.

Although most of the damage caused by lepidopteran insects to plants is caused by the larval stage, chemosensory systems have been investigated much more frequently for lepidopteran adults than for larvae. The fall armyworm Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae) is a polyphagous and worldwide pest. To understand the larval chemosensory system in S. frugiperda, we sequenced and assembled the antennae and maxillae transcriptome of larvae in the sixth instar (larval a-m) using the Illumina platform. A total of 30 putative chemosensory receptor genes were identified, and these receptors included 11 odorant receptors (ORs), 4 gustatory receptors (GRs), and 15 ionotropic receptors/ionotropic glutamate receptors (IRs/iGluRs). Phylogeny tests with the candidate receptors and homologs from other insect species revealed some specific genes, including a fructose receptor, a pheromone receptor, IR co-receptors, CO2 receptors, and the OR co-receptor. Comparison of the expression of annotated genes between S. frugiperda adults and larvae (larval a-m) using RT-qPCR showed that most of the annotated OR and GR genes were predominantly expressed in the adult stage, but that 2 ORs and 1 GR were highly expressed in both the adult antennae and the larval a-m. Although most of the tested IR/iGluR genes were mainly expressed in adult antennae, transcripts of 3 iGluRs were significantly more abundant in the larval a-m than in the adult antennae of both sexes. Comparison of the expression levels of larval a-m expressed chemosensory receptors among the first, fourth, and sixth instars revealed that the expression of some of the genes varied significantly among different larval stages. These results increase our understanding of the chemosensory systems of S. frugiperda larvae and provide a basis for future functional studies aimed at the development of novel strategies to manage this pest.

Identification of potential key circular RNAs related to cognitive impairment after chronic constriction injury of the sciatic nerve.

Chronic neuropathic pain is commonly accompanied by cognitive impairment. However, the underlying mechanism in the occurrence of cognitive deficits under constant nociceptive irritation remains elusive. Herein, we established a chronic neuropathic pain model by chronic constriction injury (CCI) of the unilateral sciatic nerve in rats. Behavioral tests indicated that CCI rats with long-term nociceptive threshold decline developed significant dysfunction of working memory and recognitive memory starting at 14 days and lasting for at least 21 days. Afterward, circRNA expression profiles in the hippocampus of CCI and sham rats were analyzed via high-throughput sequencing to explore the potential key factors associated with cognitive impairment induced by ongoing nociception, which showed 76 differentially expressed circRNAs, 39 upregulated and 37 downregulated, in the CCI group. These differentially expressed circRNA host genes were validated to be primarily associated with inflammation and apoptotic signaling pathways according to GO/KEGG analysis and the circRNA-miRNA-mRNA network, which was also confirmed through the analysis of neuroinflammation and neuronal apoptosis. Consequently, we assumed that enhanced neuroinflammation and neuronal apoptosis might act as potential regulators of cognitive impairment induced by chronic neuropathic pain. The identification of the regulatory mechanism would provide promising clinical biomarkers or therapeutic targets in the diagnostic prediction and intervention treatment of memory deficits under neuropathic pain conditions.

The diagnostic and prognostic value of the miR-17-92 cluster in hepatocellular carcinoma: A meta-analysis.

Previous studies demonstrated that microRNAs (miRNAs) could serve as biomarkers in various cancers. This meta-analysis aimed to determine the roles of a miR-17-92 cluster in hepatocellular carcinoma (HCC). Here, eligible included studies were searched through PubMed, Embase, and Wan Fang databases up to 1st February 2022. Relevant data were extracted from each eligible study to evaluate the relationship between miRNA-17-92 cluster miRNA expression and the diagnosis and prognosis of HCC. Finally, a total of 21 studies were pooled and included in the meta-analysis, of which four articles were used for diagnostic meta-analysis and eight articles were used for prognostic meta-analysis. The pooled sensitivity, specificity, and diagnostic odds ratios (DOR) of the miR17-92 cluster for diagnosis of HCC were 0.75 [95% confidence interval (CI): 0.64-0.83], 0.73 (95% CI: 0.65-0.79), and 7.87 (95% CI: 5.36-11.54), respectively. Also, the area under the curve (AUC) for the miR-17-92 cluster when diagnosing HCC was 0.79 (95% CI: 0.76-0.83). For prognostic analysis, hazard ratios (HRs) with 95% CIs were extracted from the included studies and pooled HRs were determined to assess the associations. Patients with increased expression of miR17-92 cluster miRNA were associated with poor overall survival (OS) and recurrence-free survival (RFS) (HR=1.86, 95% CI: 1.04-3.33; HR = 4.18, 95% CI: 3.02-5.77, respectively), but not progression-free survival (PFS) (HR = 0.43, 95% CI: 0.25-0.73), while no association of the miR-17-92 cluster high-expression was detected with disease-free survival (DFS) (HR: 0.95, 95% CI: 0.21-4.34). In short, current pieces of evidence suggested that the miR-17-92 cluster may serve as a novel diagnostic and prognostic biomarker for HCC. However, given the limited study number, larger-size, multi-center, and higher-quality studies are indispensable in the future.

Causal associations of iron status and back pain risk: A Mendelian randomization study.

Background: Observational studies have previously suggested a link between iron status makers and back pain. We conducted a two-sample Mendelian randomization (MR) study to determine the putative causal relationship between systemic iron status and back pain. Materials and methods: In this MR study, a genome-wide association study (GWAS) involving 48,972 individuals was used to identify genetic instruments highly associated with systemic iron status. The outcome data (back pain) were derived from the Neale Lab consortium's summary data from the UK Biobank (85,221 cases and 336,650 controls). With the inverse variance weighted (IVW) method as the main analysis, conservative analyses (selecting SNPs with concordant change of iron status biomarkers) and liberal analyses (selecting SNPs with genome-wide significant association with each iron status biomarker) were carried out. For sensitivity analyses, the MR-Egger, MR-Egger intercept, weighted median, weighted mode, and MR based on a Bayesian model averaging approaches were used. The Cochran's Q-test was used to detect heterogeneity. Results: Back pain was associated with genetically instrumented serum iron (OR = 1.01; 95% CI = 1.00-1.02, p = 0.01), ferritin (OR = 1.02; 95% CI = 1.00-1.04, p = 0.02), and transferrin saturation (OR = 1.01; 95% CI = 1.00-1.01, p = 0.01). Furthermore, there was no evidence of a link between transferrin and the risk of back pain (OR = 0.99, 95% CI = 0.98-1.00, p = 0.08). The sensitivity analyses and Cochran's Q-test indicated that no pleiotropy or heterogeneity was detected (all p > 0.05). Conclusion: We provided potential genetic evidences for the causal associations of iron status with increased incidence of back pain. However, the evidences were weakened due to the low power. Further larger MR studies or RCTs are needed to investigate small effects.

Risk Factors for Diabetic Peripheral Neuropathy, Peripheral Artery Disease, and Foot Deformity Among the Population With Diabetes in Beijing, China: A Multicenter, Cross-Sectional Study.

Diabetic peripheral neuropathy (DPN), peripheral artery disease (PAD), and foot deformity are the most common causes of diabetic foot, which can considerably worsen the patient's quality of life. In this study, we aimed to investigate the prevalence and risk factors associated with DPN, PAD, and foot deformity among patients with diabetes living in Beijing, China. In total, 3,898 diabetes patients from 11 hospitals in Beijing were evaluated using questionnaires and physical examinations, and 3,758 patients were included in the analysis. We compared the demographic, clinical, biological characteristics, and comorbidities of patients with and without DPN, PAD, or foot deformity, and used binary logistic regression analysis to identify potential factors associated with these outcomes. Overall, 882 patients (23.5%) had DPN, 437 patients (11.6%) had PAD, and 1,117 patients (29.7%) had foot deformities, including callus. The risk factors for DPN included: age ≥40 years, a ≥10+year duration of diabetes, a body mass index of <18.5 kg/m2 or ≥24 kg/m2, a systolic blood pressure (SBP) of ≥140 mm Hg, a hemoglobin A1c (HbA1c) level of ≥7%, chronic kidney disease, and cerebrovascular disease. The risk factors for PAD included: a 15+ year diabetes duration, a body mass index of <18.5 kg/m2, a SBP of ≥140 mm Hg, a HbA1c level of ≥7%, chronic kidney disease, coronary heart disease, and cerebrovascular disease. The risk factors for skeletal foot deformities included: women, age ≥40 years, a SBP ≥140 mm Hg, and hyperlipidemia. The risk factors for callus formation included: women, a SBP ≥140 mm Hg, and hyperlipidemia. In conclusion, the prevalence of foot deformities was higher than DPN and PAD in patients with diabetes. Managing the risk factors for DPN, PAD, and foot deformity is important for reducing the risk of diabetic foot.