Global supply chains amplify economic costs of future extreme heat risk.

Evidence shows a continuing increase in the frequency and severity of global heatwaves1,2, raising concerns about the future impacts of climate change and the associated socioeconomic costs3,4. Here we develop a disaster footprint analytical framework by integrating climate, epidemiological and hybrid input-output and computable general equilibrium global trade models to estimate the midcentury socioeconomic impacts of heat stress. We consider health costs related to heat exposure, the value of heat-induced labour productivity loss and indirect losses due to economic disruptions cascading through supply chains. Here we show that the global annual incremental gross domestic product loss increases exponentially from 0.03 ± 0.01 (SSP 245)-0.05 ± 0.03 (SSP 585) percentage points during 2030-2040 to 0.05 ± 0.01-0.15 ± 0.04 percentage points during 2050-2060. By 2060, the expected global economic losses reach a total of 0.6-4.6% with losses attributed to health loss (37-45%), labour productivity loss (18-37%) and indirect loss (12-43%) under different shared socioeconomic pathways. Small- and medium-sized developing countries suffer disproportionately from higher health loss in South-Central Africa (2.1 to 4.0 times above global average) and labour productivity loss in West Africa and Southeast Asia (2.0-3.3 times above global average). The supply-chain disruption effects are much more widespread with strong hit to those manufacturing-heavy countries such as China and the USA, leading to soaring economic losses of 2.7 ± 0.7% and 1.8 ± 0.5%, respectively.

Identification of CCL20 as a Prognostic Predictor for Severe Fever With Thrombocytopenia Syndrome Based on Plasma Proteomics.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS), a lethal tick-borne hemorrhagic fever, prompted our investigation into prognostic predictors and potential drug targets using plasma Olink Proteomics. METHODS: Employing the Olink assay, we analyzed 184 plasma proteins in 30 survivors and 8 nonsurvivors of SFTS. Validation was performed in a cohort of 154 patients with SFTS via enzyme-linked immunosorbent assay. We utilized the Drug-Gene Interaction Database to identify protein-drug interactions. RESULTS: Nonsurvivors exhibited 110 differentially expressed proteins as compared with survivors, with functional enrichment in the cell chemotaxis-related pathway. Thirteen differentially expressed proteins-including C-C motif chemokine 20 (CCL20), calcitonin gene-related peptide alpha, and pleiotrophin-were associated with multiple-organ dysfunction syndrome. CCL20 emerged as the top predictor of death, demonstrating an area under the curve of 1 (P = .0004) and 0.9033 (P < .0001) in the discovery and validation cohorts, respectively. Patients with CCL20 levels exceeding 45.74 pg/mL exhibited a fatality rate of 45.65%, while no deaths occurred in those with lower CCL20 levels. Furthermore, we identified 202 Food and Drug Administration-approved drugs targeting 37 death-related plasma proteins. CONCLUSIONS: Distinct plasma proteomic profiles characterize SFTS cases with different outcomes, with CCL20 emerging as a novel, sensitive, accurate, and specific biomarker for predicting SFTS prognosis.

Kinesin family member 2C promotes hepatocellular carcinoma growth and metastasis via activating MEK/ERK pathway.

The current work was intended to explore the function and mechanism of Kinesin family member 2C (KIF2C) in hepatocellular carcinoma (HCC). In this study, KIF2C expression was at a high level in HCC and indicated poor prognosis. Silencing KIF2C significantly suppressed the proliferation, migration, and invasion in HCC cells. Furthermore, silencing KIF2C markedly decreased the expression of Snail, Vimentin, p-MEK, and p-ERK, but increased E-cadherin expression in HCC cells. Moreover, we also found that MEK/ERK inhibitor U0126 could enhance the impact on cell proliferation, migration, and invasion induced by silencing KIF2C in HCC. On the contrary, MEK/ERK activator PAF could weaken the impact induced by silencing KIF2C in HCC. Thus, our findings indicate that KIF2C can promote the proliferation, migration, and invasion by activating MEK/ERK pathway in HCC.

High Levels of Circulating Cell-free DNA Are Associated With a Poor Prognosis in Patients With Severe Fever With Thrombocytopenia Syndrome.

BACKGROUND: The extensive geographical distribution and high mortality rate of severe fever with thrombocytopenia syndrome (SFTS) have made it an important threat to public health. Neutrophil extracellular traps (NETs) can be activated by a variety of pathogens and are associated with thrombocytopenia in viral infections. We aimed to identify NET production and its predictive value for disease progression and prognosis in patients with SFTS. METHODS: A prospective study was performed with a multicenter cohort of patients with SFTS (n = 112) to quantify serum NET levels. Three markers of NETs-namely, cell-free DNA (cfDNA), myeloperoxidase-DNA complexes, and lactoferrin-DNA complexes-were measured with PicoGreen double-stranded DNA assays and enzyme-linked immunosorbent assays. Receiver operating characteristic curves and multivariate regression analyses were performed to calculate the predictive value of cfDNA levels. RESULTS: SFTS was characterized by pronounced NET formation. The serum levels of NETs changed dynamically during disease progression, with an inverse pattern of the trends of platelet and neutrophil levels. High cfDNA levels were strongly associated with multiple pathological processes, including coagulopathy, myocardial damage, liver dysfunction, and the development of encephalopathy. A high level of cfDNA (>711.7 ng/mL) at the time of the initial diagnosis predicted severe illness in patients with SFTS (odds ratio, 8.285 [95% confidence interval, 2.049-33.503]; P = .003). CONCLUSIONS: This study has a high degree of clinical impact for identification of cfDNA as a useful predictive biomarker of clinical outcomes of SFTS.

The C-terminus of DSX(F5) protein acts as a novel regulatory domain in Bombyx mori.

The doublesex gene regulates the somatic sexual development of Bombyx mori by alternatively splicing into sex-specific splice forms. In our previous study, the splice form Bmdsx (F7) , which encodes the BmDSX(F5) protein, was found to be expressed in a female-specific manner and to contain a novel C-terminus. In this study, we aimed to investigate the role of this C-terminus. Two transgenic lines, L1 and L2, were constructed to ectopically express Bmdsx (F7) in males. Phenotype and W chromosome-specific polymerase chain reaction (PCR) analysis showed that developmental abnormalities and sex reversal did not occur. Moreover, the sex ratio was also normal. Quantitative PCR revealed that the expression levels of SP1 and Vg were upregulated in the fat body of transgenic males. Additionally, the expression level of PBP was downregulated in the antenna of transgenic males. The results suggested that the C-terminus of BmDSX(F5) functioned as a regulatory domain during regulation of downstream target gene expression and that BmDSX(F5) participated in the sexual development of somatic cells together with other DSX proteins in B. mori.

Preparation of Polyamide-6 Submicrometer-Sized Spheres by In Situ Polymerization.

Polyamide-6 (PA6) submicron-sized spheres are prepared by two steps: (1) anionic ring-opening polymerization of ε-caprolactam in the presence of poly(ethylene glycol)-block-poly-(propylene glycol)-block-poly(ethylene glycol)(PEG-b-PPG-b-PEG) and (2) separation of PA6 spheres by dissolving PEG-b-PPG-b-PEG from the prepared blends. The PA6 microspheres obtained are regular spherical, with diameter ranging from 200 nm to 2 µm and narrow size distribution, as confirmed by scanning electron microscopy. By comparison with PA6/PS and PA6/PEG systems, it is denominated that the PEG blocks in PEG-b-PPG-b-PEG can effectively reduce the surface tension of PA6 droplets and further decrease the diameter of the PA6 microspheres. The PPG block in PEG-b-PPG-b-PEG can prevent the PA6 droplets coalescing with each other, and isolated spherical particles can be obtained finally. The phase inversion of the PA6/PEG-b-PPG-b-PEG blends occurs at very low PEG-b-PPG-b-PEG content; the PEG-b-PPG-b-PEG phase can be removed by water easily. The whole experiment can be finished in a short time (approximately in half an hour) without using any organic solvents; it is an efficient strategy for the preparation of submicron-sized PA6 microspheres.

Ectopic expression of the male BmDSX affects formation of the chitin plate in female Bombyx mori.

Mating structures are involved in successful copulation, intromission, and/or insemination. These structures enable tight coupling between external genitalia of two sexes. During Bombyx mori copulation, the double harpagones in the external genitalia of males clasp the female chitin plate, which is derived from the larval eighth abdominal segment; abnormal development of the female chitin plate affects copulation. We report that ERK phosphorylation (p-ERK) and expression of Abdominal-B (Abd-B) in the posterior abdomen of the female adult is lower than in the male. Ectopic expression of the male-specific spliced form of B. mori doublesex (Bmdsx(M)) in females, however, up-regulates Abd-B and spitz (spi) expression, increasing EGFR signaling activity, and thus forming an abnormal chitin plate and reduced female copulation. These findings indicate that Bmdsx affects the development of the eighth abdominal segment by regulating the activity of EGFR signaling and the expression of Abd-B, resulting in an extra eighth abdominal segment (A8) in males versus the loss of this segment in adult females.

Increased cTnI Predicts Early Death in Patients with Severe Fever with Thrombocytopenia: A Multicenter Study in North China.

Background: Myocardial injury is common in severe fever with thrombocytopenia syndrome (SFTS) patients. Currently, research on the prognostic value of cardiac troponin I (cTnI) for predicting the mortality of SFTS patients, especially death within 7 days is limited. Methods: Between May 2011 and October 2022, clinical and laboratory data on admission of consecutive SFTS cases were collected from six medical centres in China. The clinical endpoint was in-hospital all-cause death within seven days. Risk factors of myocardial injury and death were analysed using multivariable regression models. Prognostic models were established using Cox regression and performance of indicators was evaluated in terms of calibration, discrimination. Results: A total of 1379 laboratory-confirmed patients were enrolled, in which 686 subjects were included for analysis. The median age was 66 years, with 48.1% of male. Eighty-seven patients died within seven days and 396 patients diagnosed with myocardial injury during hospitalization. Non-survivors had significant higher levels of cardiac indices than survivors, including cTnI, aspartic transaminase (AST) and lactate dehydrogenase (LDH). Elevated levels of cTnI (HR = 1.058, 95% CI:1.032-1.085), AST (HR = 1.191, 95% CI:1.150-1.234) and LDH (HR = 1.019, 95% CI:1.009-1.029) predicted risk of early in-hospital mortality. cTnI model performed best, with area under curve of 0.850 (0.774-0.926) and concordance index of 0.842, respectively. Statistical differences were found between high and low levels of cTnI for mortality (P<0.001) using 0.35 ng/mL as the optimal cut-off. Conclusion: The risk of early in-hospital death can be predicted by cTnI. Clinical doctors should remind vigilant concerning the elevation of cardiac enzyme as soon as possible.

Activated partial thromboplastin time predicts mortality in patients with severe fever with thrombocytopenia syndrome: A multicenter study in north China.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high lethality. This study aimed to determine whether prolonged activated partial thromboplastin time (APTT) predicted SFTS mortality. Methods: SFTS patients were enrolled from 6 hospitals in the north China. Subjects were divided into training cohort and 5 externally validation cohorts. The least absolute shrinkage and selection operator Cox regression model was performed to screen potential prognostic factors. Risk factors were analyzed using multivariable regression models. Prognostic models were established by Cox regression and random survival forest (RSF) methods, and evaluated regarding discrimination, validity and clinical benefit. Time-dependent receiver operating characteristic (ROC) curve was used to evaluate the predictive effectiveness of variables. Results: 1332 SFTS cases were included, in which 211 patients died. Six potential prognostic factors were screened, and pulse, breath, APTT and aspartic transaminase (AST) were independently associated with mortality in both training cohort (Yantai, N = 791) and external validation cohort (N = 541). APTT was steadily correlated with the fatality (HR: 1.039-1.144; all P < 0.01) in each five sub-validation cohorts (Dandong, Dalian, Tai'an, Qingdao and Beijing). RSF model with variables of APTT, AST, pulse and breath had considerable prognostic effectiveness, which APTT showed the highest prognostic ability with the area under the curve of 0.848 and 0.787 for 7-day and 14-day survival, respectively. Survival differences were found between high and low levels of APTT for mortality using 50s as the optimal cut-off. Conclusions: SFTS patients have prolonged APTT, which is an independent risk factor for fatality. APTT≥50s was recommended as a biomarker to remind physicians to monitor and treat patients more aggressively to improve clinical prognosis.

Novel female-specific trans-spliced and alternative splice forms of dsx in the silkworm Bombyx mori.

The Bombyx mori doublesex gene (Bmdsx) plays an important role in somatic sexual development. Its pre-mRNA splices in a sex-specific manner to generate two female-specific and one male-specific splice forms. The present study investigated six novel dsx variants generated by trans-splicing between female dsx transcripts and two additional novel genes, dsr1 and dsr2. Expression analysis indicated that Bmdsx-dsr1 represented splicing noise, whereas dsr2, which trans-spliced with dsx to generate five variants, regulated the expression of the female-specific B. mori dsx transcript Bmdsx(F)s. We unexpectedly found a novel exon 2n insertion during Bmdsx transcription, which did not influence the validity of the novel protein, BmDSX(F3). Ectopic expression of BmDSX(F3) repressed the pheromone-binding protein gene and the testis-specific gene A2 in males, and activated of the storage protein 1 gene. Our findings suggest that trans-splicing is a novel regulatory function of Bmdsx, which participates in female sexual development by regulating the expression of three BmDSX(F) proteins.

High­efficiency system for construction and evaluation of customized TALENs for silkworm genome editing.

Transcription activator-like effector nuclease (TALEN) possesses the characteristics of ease design and precise DNA targeting. In the silkworm Bombyx mori, TALEN has been successfully used to knockout an endogenous Bombyx gene, and shown the huge potential in functional genes research and improvement of the economical characteristics of silkworm. Thus, there is an urgent need to develop an applicable system that permits the efficient construction of customized TALEN with high activity that could efficiently induce the hereditable mutagenesis in the silkworm. In this study, we constructed an efficient assembly and evaluation system of the customized TALEN especiallly for silkworm genome editing by combination of a modified Golden Gate ligation strategy, a luciferase (LUC) reporter system in insect cell culture for binding activity and a surveyor nuclease assay system in silkworm embryos for cleavage efficiency. We showed the reliability of this system by assembling a pair of TALENs targeting a silkworm genome locus and assaying their binding and cleavage activities. The assembly strategy was convenient and efficient which allows the rapid construction of customized TALEN in less than 1 week, and the evaluation system was reliable and necessary for screening of the customized TALEN pair with high binding and cleavage activities. The results showed this system is a reliable and efficient tool for the construction of customized TALEN with high activity for gene targeting of silkworm, and will contribute to the wide application of TALEN technology in the functional gene research of silkworm.

Cre-mediated targeted gene activation in the middle silk glands of transgenic silkworms (Bombyx mori).

Cre-mediated recombination is widely used to manipulate defined genes spatiotemporally in vivo. The present study evaluated the Cre/loxP system in Bombyx mori by establishing two transgenic lines. One line contained a Cre recombinase gene controlled by a sericin-1 gene (Ser1) promoter. The other line contained a loxP-Stop-loxP-DsRed cassette driven by the same Ser1 promoter. The precise deletion of the Stop fragment was found to be triggered by Cre-mediated site-specific excision, and led to the expression of DsRed fluorescence protein in the middle silk glands of all double-transgenic hybrids. This result was also confirmed by phenotypical analysis. Hence, the current study demonstrated the feasibility of Cre-mediated site-specific recombination in B. mori, and opened a new window for further refining genetic tools in silkworms.

An optimized sericin-1 expression system for mass-producing recombinant proteins in the middle silk glands of transgenic silkworms.

The middle silk gland (MSG) of silkworm is thought to be a potential host for mass-producing valuable recombinant proteins. Transgenic MSG expression systems based on the usage of promoter of sericin1 gene (sericin-1 expression system) have been established to produce various recombinant proteins in MSG. However, further modifying the activity of the sericin-1 expression system to yield higher amounts of recombinant proteins is still necessary. In this study, we provide an alternative modification strategy to construct an efficient sericin-1 expression system by using the hr3 enhancer (hr3 CQ) from a Chongqing strain of the Bombyx mori nuclear polyhedrosis virus (BmNPV) and the 3'UTRs of the fibroin heavy chain (Fib-HPA), the fibroin light chain (Fib-LPA), and Sericin1 (Ser1PA) genes. We first analyzed the effects of these DNA elements on expression of luciferase, and found that the combination of hr3 CQ and Ser1PA was most effective to increase the activity of luciferase. Then, hr3 CQ and Ser1PA were used to modify the sericin1 expression system. Transgenic silkworms bearing these modified sericin1 expression vectors were generated by a piggyBac transposon mediated genetic transformation method. Our results showed that mRNA level of DsRed reporter gene in transgenic silkworms containing hr3 CQ and Ser1PA significantly increased by 9 fold to approximately 83 % of that of endogenous sericin1. As the results of that, the production of recombinant RFP increased by 16 fold to 9.5 % (w/w) of cocoon shell weight. We conclude that this modified sericin-1 expression system is efficient and will contribute to the MSG as host to mass produce valuable recombinant proteins.

A global daily evapotranspiration deficit index dataset for quantifying drought severity from 1979 to 2022.

Droughts cause multiple ecological and social damages. Drought indices are key tools to quantify drought severity, but they are mainly limited to timescales of monthly or longer. However, shorter-timescale (e.g., daily) drought indices enable more accurate identification of drought characteristics (e.g., onset and cessation time) and help timely potential mitigation of adverse effects. Here, we propose a dataset of a daily drought index named daily evapotranspiration deficit index (DEDI), which is produced for global land areas from 1979 to 2022 using actual and potential evapotranspiration data. Validation efforts show that the DEDI dataset can well identify dry and wet variations in terms of spatial patterns and temporal evolutions when compared with other available drought indices on a daily scale. The dataset also has the capability to capture recent drying trends and to detect ecology- or agriculture-related droughts. Overall, the DEDI dataset is a step forward in facilitating drought monitoring and early warning at higher temporal resolution than other compared existing products.

Comparative efficacy of exercise training processes in improving nonalcoholic fatty liver disease: a systematic review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis aimed to evaluate the efficacy of exercise training in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: We searched PubMed, Cochrane Library, Web of Science, and Embase for relevant research from January 2001 to December 2021. The efficacy of exercise training was analyzed. RESULTS: A total of 21 articles, involving 1733 patients, were included. Exercise training, including resistance training, aerobic exercise training, and high-intensity training, showed the efficacy in reducing weight (MD = 3.46, 95% CI [1.94, 4.98]), BMI (MD = 0.89, 95% CI [0.17, 1.61]), and ALT (MD = 6.66, 95% CI [3.27, 10.04]) and AST (MD = 3.14, 95% CI [0.35, 5.93]) levels in patients with NAFLD. When the exercise training lasted for ≥ 20 weeks, the total cholesterol (TC) (MD = 0.13, 95% CI [0.04, 0.22]), triglyceride (TG) (MD = 0.29, 95% CI [0.12, 0.47]), and blood glucose (GLU) (MD = - 0.18, 95% CI [0.10, 0.26]) levels significantly reduced. Compared with the exercise training group, the exercise training combined with probiotics group showed more efficiency in reducing the ALT, AST, TG, and TC levels. However, the exercise training combined with a hypoglycemic agent group showed no obvious efficiency compared with the exercise training group. CONCLUSION: Exercise training can improve NAFLD. The improvement was more obvious when exercise was performed for ≥ 20 weeks. Probiotics may enhance the efficiency of exercise training.

Comprehensive analysis of an autophagy-related prognostic model for predicting survival based on TCGA and ICGC database in hepatocellular carcinoma patients.

Background: There is accumulating evidence that autophagic activity is crucial to the development of hepatocellular carcinoma (HCC). Thus, we sought to develop a predictive model based on autophagy-related genes (ARGs) to forecast the prognosis of HCC patients. Methods: Based on expression data from The Cancer Genome Atlas (TCGA) and ARGs from Human Autophagy Database (HADb), the differentially expressed ARGs were screened. The prognosis-related ARGs were identified using a univariate Cox regression analysis. Using multivariate Cox regression analysis, a prognostic model was developed. To assess the predictive value of the model, receiver operating characteristic (ROC) curve, Kaplan-Meier curve, and multivariable Cox regression analyses were conducted. A data cohort gathered independently from the International Cancer Genome Consortium (ICGC) database further verified the model's predictive accuracy. The immune landscape was generated using the TIMER and CIBERSORT algorithms. Finally, the correlation between the prognostic signature and gene mutation status was analyzed by employing "maftools" package. Results: We identified a novel prediction model based on the ARGs of PLD1 and SLC36A1 with significant prognostic values for HCC in both univariate and multivariate Cox regression analysis, and patients were classified into high- or low-risk groups based on their risk scores. High-risk patients had significantly shorter overall survival (OS) times than low-risk patients (P=5e-4). According to the ROC curve analysis, the risk score had a higher predictive value than the other clinical characteristics. Prognostic nomograms were also performed to visualize the relationship between individual predictors and survival rates in patients with HCC. Further, an external independent cohort of ICGC patients provided additional confirmation of the predictive efficacy of the model. We subsequently analyzed the differential immune densities of the two groups and discovered that various immune cells, including naïve B cells, resting memory cluster of differentiation (CD)4 T cells, regulatory T cells, M2 macrophages, and neutrophils, had considerably larger infiltrating densities in the high-risk group than the low-risk group. Conclusions: We established a robust autophagy-related risk model having a certain prediction accuracy for predicting the prognosis of HCC patients. Our findings will contribute to the definition of prognosis and establishment of personalized treatment interventions for HCC patients.

Genome-Wide Identification of M14 Family Metal Carboxypeptidases in Antheraea pernyi (Lepidoptera: Saturniidae).

The M14 family metal carboxypeptidase genes play an important role in digestion and pathogenic infections in the gut of insects. However, the roles of these genes in Antheraea pernyi (Guérin-Méneville, 1855) remain to be analyzed. In the present study, we cloned a highly expressed M14 metal carboxypeptidase gene (ApMCP1) found in the gut and discovered that it contained a 1,194 bp open reading frame encoding a 397-amino acid protein with a predicted molecular weight of 45 kDa. Furthermore, 14 members of the M14 family metal carboxypeptidases (ApMCP1-ApMCP14) were identified in the A. pernyi genome, with typical Zn_pept domains and two Zn-anchoring motifs, and were further classified into M14A, M14B, and M14D subfamilies. Expression analysis indicated that ApMCP1 and ApMCP9 were mainly expressed in the gut. Additionally, we observed that ApMCP1 and ApMCP9 displayed opposite expression patterns after starvation, highlighting their functional divergence during digestion. Following natural infection with baculovirus NPV, their expression was significantly upregulated in the gut of A. pernyi. Our results suggest that the M14 family metal carboxypeptidase genes are conservatively digestive enzymes and evolutionarily involved in exogenous pathogenic infections.

Pupal Diapause Termination and Transcriptional Response of Antheraea pernyi (Lepidoptera: Saturniidae) Triggered by 20-Hydroxyecdysone.

The pupal diapause of univoltine Antheraea pernyi hampers sericultural and biotechnological applications, which requires a high eclosion incidence after artificial diapause termination to ensure production of enough eggs. The effect of pupal diapause termination using 20-hydroxyecdysone (20E) on the eclosion incidence has not been well-documented in A. pernyi. Here, the dosage of injected 20E was optimized to efficiently terminate pupal diapause of A. pernyi, showing that inappropriate dosage of 20E can cause pupal lethality and a low eclosion incidence. The optimal ratio of 20E to 1-month-old pupae was determined as 6 µg/g. Morphological changes showed visible tissue dissociation at 3 days post-injection (dpi) and eye pigmentation at 5 dpi. Comprehensive transcriptome analysis identified 1,355/1,592, 494/203, 584/297, and 1,238/1,404 upregulated and downregulated genes at 1, 3, 6, and 9 dpi, respectively. The 117 genes enriched in the information processing pathways of "signal transduction" and "signaling molecules and interaction" were upregulated at 1 and 3 dpi, including the genes involved in FOXO signaling pathway. One chitinase, three trehalase, and five cathepsin genes related to energy metabolism and tissue dissociation showed high expression levels at the early stage, which were different from the upregulated expression of four other chitinase genes at the later stage. Simultaneously, the expression of several genes involved in molting hormone biosynthesis was also activated between 1 and 3 dpi. qRT-PCR further verified the expression patterns of two ecdysone receptor genes (EcRB1 and USP) and four downstream response genes (E93, Br-C, ßFTZ-F1, and cathepsin L) at the pupal and pharate stages, respectively. Taken together, these genes serve as a resource for unraveling the mechanism underlying pupal-adult transition; these findings facilitate rearing of larvae more than once a year and biotechnological development through efficient termination of pupal diapause in A. pernyi in approximately half a month.

LINC00238 inhibits hepatic carcinoma progression by activating TMEM106C­mediated apoptosis pathway.

The present study aimed to explore the regulatory mechanism of long intergenic non­protein coding (LINC)00238 in hepatocellular carcinoma (HCC). LINC00238 expression in HCC tissues and cell lines was measured using reverse transcription­quantitative PCR. LncTar was used to predict the binding sites between LINC00238 and transmembrane protein 106C (TMEM106C). Survival analysis of LINC00238, TMEM106C and activating transcription factor 3 (ATF3) in patients with HCC was performed based on TCGA data. The proliferation, apoptosis, migration, and invasion of HCC cells were measured by 3­(4,5­dimethylthiazol­2­yl)­5­(3­carboxymethoxyphenyl)­2­(4­sulfophenyl)­2H­tetrazolium assay, flow cytometer, wound healing and Transwell assays, respectively. LINC00238 promoted apoptosis and inhibited proliferation, migration and invasion of HCC cells. LINC00238 was downregulated in HCC. TMEM106C was a target of LINC00238 and TMEM106C expression was negatively regulated by LINC00238. TMEM106C suppressed the apoptosis pathway and decreased the expression of caspase­7, tissue inhibitor of metalloproteinase 2, programmed cell death 4 and ATF3. Notably, ATF3 was the upstream promoter of LINC00238 and positively regulated LINC00238 expression. In conclusion, LINC00238 inhibited HCC progression by inhibiting TMEM106 expression and activating the TMEM106C­mediated apoptosis pathway.

A Gut-Specific LITAF-Like Gene in Antheraea pernyi (Lepidoptera: Saturniidae) Involved in the Immune Response to Three Pathogens.

Antheraea pernyi (Guérin-Méneville 1855) is an important resource for silk, food, and biohealth products; however, exogenous pathogens largely affect the commercial application potential of this species. Since the gut is a key organ for the digestion and absorption of nutrients as well as for immune defense, we used comparative transcriptome analysis to screen for a gut-specific molecular tool for further functional research in A. pernyi. In total, 3,331 differentially expressed genes (DEGs) were identified in the gut compared with all other pooled tissues of A. pernyi, including 1,463 upregulated genes in the gut. Among these, we further focused on a lipopolysaccharide-induced tumor necrosis factor-α factor (LITAF) gene because of its high gut-specific expression and the presence of a highly conserved SIMPLE-like domain, which is related to the immune response to pathogenic infections in many species. The cDNA sequence of ApLITAF was 447-bp long and contained a 243-bp open reading frame encoding an 80-amino acid protein. Immune challenge assays indicated that ApLITAF expression was significantly upregulated in the gut of A. pernyi naturally infected with nucleopolyhedrovirus (NPV) or fed leaves infected with the gram-negative bacterium Escherichia coli (Migula 1895) and the gram-positive bacterium Bacillus subtilis (Ehrenberg 1835). Cell transfection showed that ApLITAF localized to the lysosome. Collectively, these results suggested that ApLITAF played a role in the immune response of A. pernyi and could facilitate the future research and breeding application in this species.