Hypoxia-driven lncRNA CTD-2510F5.4: a potential player in hepatocellular carcinoma's prognostic stratification, cellular behavior, tumor microenvironment, and therapeutic response.

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly aggressive cancer with limited therapeutic options. Hypoxia is a common feature of the tumor microenvironment that reportedly promotes tumorigenesis. Long non-coding RNAs (lncRNAs) are a class of regulatory molecules with diverse functions in cancer biology. This study aimed to identify hypoxia-induced lncRNAs associated with HCC and evaluate their potential as prognostic and therapeutic biomarkers. METHODS: We employed microarray and The Cancer Genome Atlas (TCGA) data to identify hypoxia-induced lncRNAs in HCC. Subsequently, we focused on CTD-2510F5.4, a candidate lncRNA, and predicted its functional roles in HCC using Gene Ontology (GO) and Guilt-by-Association (GBA) analyses. We validated its expression under hypoxia in Huh7 and HepG2 cells using RT-PCR. Functional assays, including CCK8, wound-healing, and transwell assays, were performed to assess the effects of CTD-2510F5.4 overexpression on HCC cell proliferation, invasion, and metastasis potential. Furthermore, we investigated the association between CTD-2510F5.4 expression and patient prognosis, tumor mutation signature, immune microenvironment characteristics, and therapeutic response to different treatment modalities. RESULTS: Our data demonstrated a significant upregulation of CTD-2510F5.4 expression in response to hypoxia. Functional enrichment analyses revealed the involvement of CTD-2510F5.4 in cell cycle regulation, E2F targets, G2M checkpoint control, and MYC signaling pathways. Functionally, CTD-2510F5.4 overexpression promoted HCC cell proliferation, invasion, and metastasis. Patients with high CTD-2510F5.4 expression exhibited a worse prognosis, a higher prevalence of TP53 mutations, increased infiltration by immunosuppressive regulatory T cells, elevated expression of immune checkpoint molecules, and higher TIDE scores indicative of immune dysfunction and exclusion. Notably, patients with low CTD-2510F5.4 expression displayed greater sensitivity to immunotherapy and antiangiogenic therapy, while those with high expression responded better to chemotherapy. CONCLUSION: Our findings suggest that CTD-2510F5.4 plays a critical role in HCC progression and immune modulation. Its potential as a prognostic biomarker and a predictor of therapeutic response warrants further investigation for personalized treatment strategies in HCC patients.

Identification of C1q/TNF-related protein 4 as a novel appetite-regulating peptide that reduces food intake in Siberian sturgeon (Acipenser baerii).

Emerging findings point to a role for C1q/TNF-related protein 4 (CTRP4) in feeding in mammals. However, it remains unknown whether CTRP4 regulates feeding in fish. This study aimed to determine the feeding regulation function of CTRP4 in Siberian sturgeon (Acipenser baerii). In this study, the Siberian sturgeon ctrp4 (Abctrp4) gene was cloned, and Abctrp4 mRNA was shown to be highly expressed in the hypothalamus. In the hypothalamus, Abctrp4 mRNA decreased during fasting and reversed after refeeding. Subsequently, we obtained the AbCTRP4 recombinant protein by prokaryotic expression and optimized the expression and purification conditions. Siberian sturgeon (81.28 ± 14.75 g) were injected intraperitoneally using 30, 100, and 300 ng/g Body weight (BW) AbCTRP4 to investigate its effect on feeding. The results showed that 30, 100, and 300 ng/g BW of the AbCTRP4 significantly reduced the cumulative food intake of Siberian sturgeon at 1, 3, and 6 h. Finally, to investigate the potential mechanism of CTRP4 feeding inhibition, 300 ng/g BW AbCTRP4 was injected intraperitoneally. The findings demonstrated that AbCTRP4 treatment for 1 h significantly promoted the mRNA levels of anorexigenic peptides (pomc, cart, and leptin) while suppressing the mRNA abundances of orexigenic peptides (npy and agrp).In addition, the jak2/stat3 pathway in the hypothalamus was significantly activated after 1 h of AbCTRP4 treatment. In conclusion., this study confirms the anorexigenic effect of CTRP4 in Siberian sturgeon.

Dietary exposure to 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) induces oxidative damage promoting cell apoptosis primarily via mitochondrial pathway in the hepatopancreas of carp, Cyprinus carpio.

To investigate the mechanisms of BDE-47 on hepatotoxicity in fish, this study examined the effects of dietary exposure to BDE-47 (40 and 4000 ng/g) on carp for 42 days. The results showed that BDE-47 significantly increased carp's condition factor and hepatosomatic index. Pathological results revealed unclear hepatic cord structure, hepatocytes swelling, cellular vacuolization, and inflammatory cell infiltration in the hepatopancreas of carp. Further investigation showed that ROS levels significantly increased on days 7, 14, and 42. Moreover, the activities of antioxidant enzymes SOD, GSH, CAT, and GST increased significantly from 1 to 7 days, and the transcription levels of antioxidant enzymes CAT, Cu-Zn SOD, Mn-SOD, GST, and GPX, and antioxidant pathway genes Keap1, Nrf2, and HO-1 changed significantly at multiple time-points during the 42 days. The results of apoptosis pathway genes showed that the mitochondrial pathway genes Bax, Casp3, and Casp9 were significantly upregulated and Bcl2 was significantly downregulated, while the transcription levels of FADD and PERK were significantly enhanced. These results indicate that BDE-47 induced oxidative damage in hepatopancreas, then it promoted cell apoptosis mainly through the mitochondrial pathway. This study provides a foundation for analyzing the mechanism of hepatotoxicity induced by BDE-47 on fish.

Neglected function of gastrin to reduce feeding in Siberian sturgeon (Acipenser baerii) via cholecystokinin receptor B.

Gastrin is an important intragastrointestinal hormone, but reports on its regulation of feeding behavior in fish are still scarce. This study aimed to determine the feeding regulatory function of gastrin in sturgeon. In this study, a gastrin/cholecystokinin-like peptide was identified in the genomes of sturgeon and proved to be gastrin by evolutionary tree analysis. Tissue distribution of gastrin and its receptor, cholecystokinin receptor B (CCKRB), showed that both had high mRNA abundance in the hypothalamus and gastrointestinal tract. In the duodenum, gastrin and CCKRB mRNAs were reduced at 1 h of fasting, and both were also observed in the stomach and hypothalamus in response to changes in feeding status. Sulfated gastrin 17 is the major form of gastrin in vivo. Therefore, we investigated the effect of sulfated gastrin 17 on feeding by intraperitoneal injection into Siberian sturgeon using sulfated gastrin 17. The results showed that gastrin 17 significantly reduced the cumulative feeding of Siberian sturgeon in the short term (1, 3 and 6 h) and long term (1, 2, 3, 4, 5 and 7 days). Finally, we explored the potential mechanism of feeding inhibition after intraperitoneal injection of gastrin 17 for 7 consecutive days. The results showed that gastrin 17 treatment significantly increased the mRNA levels of anorexigenic peptides (cart, cck and pyy), while it had no significant effect on the mRNA abundance of orexigenic peptides (npy and agrp). In addition, gastrin 17 treatment significantly affected the expression of appetite signaling pathways in the hypothalamus, such that the mRNA expression of ampkα1 was significantly reduced, whereas the mRNA abundance of stat3, mtor and s6k was significantly increased. In conclusion, the present study confirmed the anorectic effect of gastrin on Siberian sturgeon.

GSTZ1-1 Deficiency Activates NRF2/IGF1R Axis in HCC via Accumulation of Oncometabolite Succinylacetone.

The IGF1R signaling is important in the malignant progression of cancer. However, overexpression of IGF1R has not been properly assessed in HCC. Here, we revealed that GSTZ1-1, the enzyme in phenylalanine/tyrosine catabolism, is downregulated in HCC, and its expression was negatively correlated with IGF1R. Mechanistically, GSTZ1-1 deficiency led to succinylacetone accumulation, alkylation modification of KEAP1, and NRF2 activation, thus promoting IGF1R transcription by recruiting SP1 to its promoter. Moreover, inhibition of IGF1R or NRF2 significantly inhibited tumor-promoting effects of GSTZ1 knockout in vivo. These findings establish succinylacetone as an oncometabolite, and GSTZ1-1 as an important tumor suppressor by inhibiting NRF2/IGF1R axis in HCC. Targeting NRF2 or IGF1R may be a promising treatment approach for this subset HCC.

SPOP inhibits HBV transcription and replication by ubiquitination and degradation of HNF1α.

Hepatitis B virus (HBV) infection remains a significant public health burden worldwide. The persistence of covalently closed circular DNA (cccDNA) within the nucleus of infected hepatocytes is responsible for the failure of antiviral treatments. The ubiquitin proteasome system (UPS) has emerged as a promising antiviral target, as it can regulate HBV replication by promoting critical protein degradation in steps of viral life cycle. Speckle-type POZ protein (SPOP) is a critical adaptor for Cul3-RBX1 E3 ubiquitin ligase complex, but the effect of SPOP on HBV replication is less known. Here, we identified SPOP as a novel host antiviral factor against HBV infection. SPOP overexpression significantly inhibited the transcriptional activity of HBV cccDNA without affecting cccDNA level in HBV-infected HepG2-NTCP and primary human hepatocyte cells. Mechanism studies showed that SPOP interacted with hepatocyte nuclear factor 1α (HNF1α), and induced HNF1α degradation through host UPS pathway. Moreover, the antiviral role of SPOP was also confirmed in vivo. Together, our findings reveal that SPOP is a novel host factor which inhibits HBV transcription and replication by ubiquitination and degradation of HNF1α, providing a potential therapeutic strategy for the treatment of HBV infection.

Neuromedin U regulates food intake of Siberian sturgeon through the modulation of central and peripheral appetite factors.

Neuromedin U (NMU) has a critical function on the regulation of food intake in mammals, while the information is little in teleost. To investigate the function of NMU on appetite regulation of Siberian sturgeon (Acipenser baerii), this study first cloned nmu cDNA sequence that encoded 154 amino acids including NMU-25 peptide. Besides, the results showed that nmu mRNA was widely distributed in various tissues especially in the hypothalamus and telencephalon. The results of nutritional status (pre-feeding and post-feeding, fasting and re-feeding) experiments showed that nmu mRNA expression was significantly decreased at 1 and 3 h after feeding in different brain regions. Similarly, after feeding, the expression of nmu significantly decreased in peripheral tissues. Moreover, nmu expression in the hypothalamus was significantly increased after fasting 1 d, but decreased after fasting 17 d, which was significantly reversed after re-feeding. However, other brain regions like telencephalon and peripheral tissues like oesophagus, intestinum valvula and liver have different change patterns. Further study showed that acute i.c.v. and i.p. injection of NMU and chronic i.p. injection of NMU significantly reduced the food intake in a dose-dependent mode. In addition, the expressions of several critical appetite factors (nmu, aplein, cart, cck, ghrelin, npy, nucb2, pyy and ucn3) were significantly affected by acute NMU-25 administration in the hypothalamus, intestinum valvula and liver. These results indicate that NMU-25 has the anorexigenic function on food intake by affecting different appetite factors in Siberian sturgeon, which provides a foundation for further exploring the appetite regulation networks in fish.

Accurate luminance and chromaticity controls of digital colors using CIE-based RGBW algorithms.

Emerging high brightness of color displays and high signal-to-noise ratio of camera sensors require an addition of white (W) subpixels to ordinary red, green, and blue (RGB) subpixels. Conventional algorithms converting RGB signals to RGBW signals suffer from reduced chroma of highly saturated colors and complicated coordinate transformations between RGB color spaces and color spaces defined by the Commission internationale de l'éclairage (CIE). In this work, we developed a complete set of RGBW algorithms to digitally code a color in the CIE-based color spaces, making complicated processes including color space transformations and white balancing become largely unnecessary. The analytic three-dimensional gamut can be obtained so that the maximal hue and luminance of a digital frame could be simultaneously obtained. Exemplary applications in adaptive controls of the colors of an RGB display in accordance with the W component of background light validate our theory. The algorithm opens an avenue toward accurate manipulations of digital colors for RGBW sensors and displays.

Cascaded Degradation-Aware Blind Super-Resolution.

Image super-resolution (SR) usually synthesizes degraded low-resolution images with a predefined degradation model for training. Existing SR methods inevitably perform poorly when the true degradation does not follow the predefined degradation, especially in the case of the real world. To tackle this robustness issue, we propose a cascaded degradation-aware blind super-resolution network (CDASRN), which not only eliminates the influence of noise on blur kernel estimation but also can estimate the spatially varying blur kernel. With the addition of contrastive learning, our CDASRN can further distinguish the differences between local blur kernels, greatly improving its practicality. Experiments in various settings show that CDASRN outperforms state-of-the-art methods on both heavily degraded synthetic datasets and real-world datasets.

Kallistatin prevents ovarian hyperstimulation syndrome by regulating vascular leakage.

Angiogenesis and increased permeability are essential pathological basis for the development of ovarian hyperstimulation syndrome (OHSS). Kallistatin (KS) is an endogenous anti-inflammatory and anti-angiogenic factor that participates in a variety of diseases, but its role in OHSS remains unknown. In this study, treating a human ovarian granulosa-like tumour cell line KGN and human primary granulosa cells (PGCs) with human chorionic gonadotropin (hCG) reduced the expression of KS, but increased the expression of VEGF. Furthermore, we found that KS could attenuate the protein level of VEGF in both KGN cells and human PGCs. More interestingly, we observed that exogenous supplementation of KS significantly inhibited a series of signs of OHSS in mice, including weight gain, ovarian enlargement, increased vascular permeability and up-regulation of VEGF expression. In addition, KS was proved to be safe on mice ovulation, progression of normal pregnancy and fetus development. Collectively, these findings demonstrated that KS treatment prevented OHSS, at least partially, through down-regulating VEGF expression. For the first time, these results highlight the potential preventive value of KS in OHSS.

Clinical application of noninvasive chromosomal screening for elective single-blastocyst transfer in frozen-thawed cycles.

BACKGROUND: The objective of this study was to explore the clinical application of noninvasive chromosomal screening (NICS) for elective single-blastocyst transfer (eSBT) in frozen-thawed cycles. METHODS: This study retrospectively analysed the data of 212 frozen-thawed single-blastocyst transfers performed in our centre from January 2019 to July 2019. The frozen embryos were selected based on morphological grades and placed in preincubation for 6 h after warming. Then spent microdroplet culture media of frozen-thawed blastocysts were harvested and subjected to NICS. The clinical outcomes were evaluated and further stratified analysis were performed, especially different fertilization approaches. RESULTS: The clinical pregnancy, ongoing pregnancy, and live birth rates in the euploidy group were significantly higher than those in the aneuploidy group (56.2% versus 29.4%) but were nonsignificantly different from those in the chaotic abnormal/NA embryos group (56.2% versus 60.4%). Compared with day6 (D6) blastocysts, D5 blastocysts had a nonsignificantly different euploidy rate (40.4% versus 48.1%, P = 0.320) but significantly increased clinical pregnancy (57.7% versus 22.2%, P < 0.001), ongoing pregnancy (48.1% versus 14.8%, P < 0.001), and live birth rates (48.1% versus 13.0%, P < 0.001). The percentage of chaotic abnormal/NA embryos group was significantly higher among D5 embryos than among D6 embryos (30.1% versus 11.1%, P = 0.006). The percentage of aneuploid embryos was higher among the embryos with lower morphological quality(21.5% among 'good' embryos versus 34.6% among 'fair' embryos versus 46.0% among 'poor' embryos, P = 0.013); correspondingly, the overall clinical pregnancy, ongoing pregnancy and live birth rate rates showed similar declines. CONCLUSIONS: NICS combined with morphological assessment is an effective tool to guide frozen-thawed SBT. The optimal embryo for SBT is a 'euploid embryo with good morphology', followed sequentially by a 'chaotic abnormal/NA embryo with good morphology', 'euploid embryo with fair morphology', and 'chaotic abnormal/NA embryo with fair morphology'.

Distinct immune responses in the early phase to natural SARS-CoV-2 infection or vaccination.

Immune responses elicited by viral infection or vaccination play key roles in the viral elimination and the prevention of reinfection, as well as the protection of healthy persons. As one of the most widely used Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, there have been increasing concerns about the necessity of additional doses of inactivated vaccines, due to the waning immune response several months after vaccination. To further optimize inactivated SARS-CoV-2 vaccines, we compared immune responses to SARS-CoV-2 elicited by natural infection and immunization with inactivated vaccines in the early phase. We observed the lower antibody levels against SARS-CoV-2 spike (S) and nucleocapsid (N) proteins in the early phase of postvaccination with a slow increase, compared to the acute phase of SARS-CoV-2 natural infection. Specifically, IgA antibodies have the most significant differences. Moreover, we further analyzed cytokine expression between these two groups. A wide variety of cytokines presented high expression in the infected individuals, while a few cytokines were elicited by inactivated vaccines. The differences in antibody responses and cytokine levels between natural SARS-CoV-2 infection and vaccination with the inactivated vaccines may provide implications for the optimization of inactivated SARS-CoV-2 vaccines and the additional application of serological tests.

Ghrelin-Ghrelin receptor (GSHR) pathway via endocannabinoid signal affects the expression of NPY to promote the food intake of Siberian sturgeon (Acipenser baerii).

Previous data suggested that activation of endocannabinoid receptor 1 (CB1) was necessary for the orexigenic effect of Ghrelin in rodents, but the information is limited in teleosts. To investigate the feeding regulation pathway of Ghrelin and CB1 in Siberian sturgeon (Acipenser baerii), this study first identified the Ghrelin (345 bp, complete coding sequence) and Ghrelin receptor (GHSR, 500 bp, partial coding sequence) sequences, and then detected their tissue distribution patterns, which showed that Ghrelin is mainly distribution in peripheral tissues, while GSHR is mainly in different brain divisions. Besides, the qPCR before and after feeding showed that the mRNA expressions of Ghrelin and GHSR were inhibited after feeding in telencephalon, diencephalon and mesencephalon. Subsequently, the food intake and appetite factor expressions were measured by i.c.v. co-injection of Ghrelin and GSHR antagonist. The results showed that Ghrelin promoted the food intake of Siberian sturgeon, which was reversed by its receptor antagonist. Besides, i.c.v. injection of Ghrelin decreased telencephalon CART expression while increased NPY expression in the three brain regions. In addition, to further explore the relationship of Ghrelin and CB1 signal regulating feeding, the co-injection of Ghrelin and CB1 antagonists was performed. The results showed that AM6545 (CB1 peripheral restricted antagonist) failed to affect the orexigenic effect of Ghrelin and the expression pattern of NPY mRNA in the telencephalon. While in the diencephalon, the increase of food intake and NPY mRNA expression induced by Ghrelin was completely reversed by Rimonabant (CB1 global antagonist). These results indicate Ghrelin-GSHR pathway promotes the food intake of Siberian sturgeon by inducing the expression of NPY in the diencephalon, and the stimulating effect will be reversed by cannabinoid receptor antagonism. This study provides a foundation for understanding the pathways Ghrelin and CB1 signals in appetite regulation of the teleost.

Implications of Free and Occluded Fine Colloids for Organic Matter Preservation in Arable Soils.

Colloidal organo-mineral associations contribute to soil organic matter (OM) preservation and mainly occur in two forms: (i) as water-dispersible colloids that are potentially mobile (free colloids) and (ii) as building units of soil microaggregates that are occluded inside them (occluded colloids). However, the way in which these two colloidal forms differ in terms of textural characteristics and chemical composition, together with the nature of their associated OM, remains unknown. To fill these knowledge gaps, free and occluded fine colloids <220 nm were isolated from arable soils with comparable organic carbon (Corg) but different clay contents. Free colloids were dispersed in water suspensions during wet-sieving, while occluded colloids were released from water-stable aggregates by sonication. The asymmetric flow field-flow fractionation analysis on the free and occluded colloids suggested that most of the 0.6-220 nm fine colloidal Corg was present in size fractions that showed high abundances of Si, Al, and Fe. The pyrolysis-field ionization mass spectrometry revealed that the free colloids were relatively rich in less decomposed plant-derived OM (i.e., lipids, suberin, and free fatty acids), whereas the occluded colloids generally contained more decomposed and microbial-derived OM (i.e., carbohydrates and amides). In addition, a higher thermal stability of OM in occluded colloids pointed to a higher resistance to further degradation and mineralization of OM in occluded colloids than that in free colloids. This study provides new insights into the characteristics of subsized fractions of fine colloidal organo-mineral associations in soils and explores the impacts of free versus occluded colloidal forms on the composition and stability of colloid-associated OM.

Identification, tissue distribution, and anorexigenic effect of amylin in Siberian sturgeon (Acipenser baeri).

Amylin is a 37-amino acid polypeptide that has been found to be involved in feeding regulation in some mammals, birds, and goldfish. We cloned amylin of Siberian sturgeon and detected its distribution pattern in 15 tissues. The expression levels in the periprandial period (pre-and post-feeding), the changes in the food intake, and the expression levels of related appetite factors after the intraperitoneal injection of amylin were detected. The expression of amylin was found to be the highest in the hypothalamus. Compared with 1 h pre-feeding, the expression levels of amylin in the hypothalamus and duodenum were increased significantly 1 h post-feeding. Compared with the control group (saline), intraperitoneal injection of 50 ng/g, 100 ng/g, and 200 ng/g of amylin significantly inhibited food intake at 1 h post injection, but not at 3 h and 6 h. The injection of 50 ng/g, 100 ng/g, and 200 ng/g amylin significantly inhibited the cumulative feed. After 1 h of 50 ng/g amylin injection, the levels of MC4R and somatostatin in the hypothalamus increased significantly, while the levels of amylin and NPY decreased significantly. The levels of CCK in the valvular intestine were increased significantly. Insulin in the duodenum was also increased significantly, but there was no significant change in ghrelin in the duodenum. These results show that amylin inhibits feeding in Siberian sturgeon by down-regulating the appetite-stimulating factor NPY and up-regulating the appetite-suppressing factors somatostatin, MC4R, CCK, and insulin. This study provides a theoretical basis for studying the feeding function and action mechanisms of amylin in Siberian sturgeon.

Transcriptome Reveals the Effects of Early Weaning on Lipid Metabolism and Liver Health of Yangtze Sturgeon (Acipenser dabryanus).

The Yangtze sturgeon (Acipenser dabryanus) has recently been declared extinct in the wild, and artificial breeding is the only means to protect its germplasm resources, but it has difficulty in weaning (from live prey to artificial food). In this study, we first performed a histological observation, enzyme-activity determination, and transcriptome sequencing on the livers of juvenile Yangtze sturgeons, and we then cloned five critical genes of lipid metabolism according to the transcriptome-sequencing results. We designed a weaning experiment to analyze their expression levels during weaning. The results showed that the density of hepatocytes and the transaminase activity of the juveniles failed to wean. The differentially expressed genes were enriched significantly in the pathways involving steroid synthesis, amino acid metabolism, and pancreatic secretion. It was found that the mRNA level of the fatty acid-synthesis gene decreased, and the mRNA level of the lipolysis gene increased significantly during weaning. The results of this research indicated that weaning could affect the liver health of Yangtze sturgeon, and it could affect the liver lipid metabolism by inhibiting fatty acid synthesis and promoting lipolysis. This study enhances our understanding of the impact of weaning on the lipid metabolism in fish.

The insulin gene as an energy homeostasis biomarker in Yangtze sturgeon (Acipenser dabryanus).

Insulin plays an important role in maintaining energy homeostasis and has the potential to be an indicator of energy homeostasis in the Yangtze sturgeon, Acipenser dabryanus. In this study, the Yangtze sturgeon insulin (Adinsulin) was cloned and characterized. To evaluate the possibility of insulin as an energy state assessment indicator, quantification real-time PCR (qRT-PCR) was used to evaluate expression changes in different tissues (the whole brain, esophagus, cardiac stomach, pyloric stomach, pyloric caeca, duodenum, valvula intestine, rectum, liver, pancreas, spleen, kidney, heart, muscle, gill and eye) from 6 fish (average weight 325.7 ± 22.3 g) and in three experiments including postprandial, fasting and re-feeding, and glucose tolerance treatment in which fish were divided into two groups including a group that administered a glucose solution (1 ul/g body weight) and another group that administered sterile water as control. In these three experiments, 6 fish were sampled, respectively, then been used to evaluate expression changes of insulin. All fish in feeding groups were fed in tanks (60.0 cm × 50.0 cm × 40.0 cm) with a commercial diet (crude protein ≥ 40%, crude fat ≥ 12%, coarse fiber ≤ 6%, crude ash ≤ 18%; TONGWEI CO., LTD, China) once a day at 16:00. The result showed that Adinsulin was highly expressed in the pancreas, which was the basis for the next experiment to use the pancreas as the test target. Adinsulin expression significantly increased 1 h after feeding and decreased rapidly after 3 h of feeding, but it was still significantly higher than that of the group without feeding (P < 0.01). Compared to the feeding group, the expression of Adinsulin was significantly reduced in the fasting group of 3 days (P < 0.01), 6 days (P < 0.01), 10 days (P < 0.05), 11 days (P < 0.05) and 13 days (P < 0.01) and was no significant difference in re-feeding for 1st day, 2nd day and 4th day, but there was difference between re-feeding group and fasting group. After glucose tolerance treatment, serum glucose levels increased significantly (P < 0.05), accompanied by a significant increase (P < 0.001) in insulin expression. This study result shows that insulin has the capacity to measure the energy homeostasis of Yangtze sturgeon. Further development of detection methods for sturgeon plasma or serum insulin will avoid slaughtering animals and is more practical in energy homeostasis assessment.

Cloning and expression of kiss genes and regulation of feeding in Siberian sturgeon (Acipenser baerii).

In 1996, kiss was reported to regulate feeding in mammals, but studies are limited in fish. Our study aimed to explore the possible role of kiss in the regulation of feeding in Siberian sturgeon (Acipenser baerii). kiss1 and kiss2 were cloned, and the expression patterns were analyzed in Siberian sturgeon. The complete coding regions of kiss1 and kiss2 genes were 393 and 471 bp. Both kiss1 and kiss2 showed the highest expression level in the hypothalamus. During the periprandial and fasting experiments, the expression of kiss1 and kiss2 highly significantly increased in the hypothalamus after feeding (P < 0.01). Compared with the feeding group, in hypothalamus, kiss1 expression in the fasting group highly significantly decreased (P < 0.01). In contrast, kiss2 expression had no significant difference on days 1 and 7 (P > 0.05) but highly significantly increased on day 14 (P < 0.01). Subsequently, the feeding function was verified by intraperitoneal (i.p.) injection of Kp1(10) and Kp1(10) into fish. The results showed that i.p. injection of 1 µg/g BW Kp1(10) or 0.01 µg/g BW Kp2(10) could significantly reduce 0-1 h food intake (P < 0.05) and affected the expression levels of apelin, ghrelin, leptin, nmu, etc. in the hypothalamus. These results suggested that kiss1 plays an anorexic role in both short- and long-term feeding regulation, while kiss2 plays a short-term anorexic and long-term orexigenic role. This study described kiss as a novel regulator of appetite in fish and laid the groundwork for further studies focused on physiological function. HIGHLIGHTS: • The kiss1 and kiss2 of Siberian sturgeon were cloned. • The expression levels of kiss1 and kiss2 mRNA were the highest in the hypothalamus. • Postprandial hypothalamic kiss1 and kiss2 expression levels increased in the periprandial experiment. • In the fasting test, the expression of hypothalamic kiss1 decreased after fasting, while the expression of kiss2 increased after fasting on the 14th day. • Siberian sturgeon food intake was reduced, and appetite factors expression levels in the hypothalamus were altered after intraperitoneal injection of Kp1(10) and Kp2(10).

Longitudinal Dynamics of the Neutralizing Antibody Response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global pandemic with no licensed vaccine or specific antiviral agents for therapy. Little is known about the longitudinal dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific neutralizing antibodies (NAbs) in patients with COVID-19. METHODS: Blood samples (n = 173) were collected from 30 patients with COVID-19 over a 3-month period after symptom onset and analyzed for SARS-CoV-2-specific NAbs using the lentiviral pseudotype assay, coincident with the levels of IgG and proinflammatory cytokines. RESULTS: SARS-CoV-2-specific NAb titers were low for the first 7-10 days after symptom onset and increased after 2-3 weeks. The median peak time for NAbs was 33 days (interquartile range [IQR], 24-59 days) after symptom onset. NAb titers in 93.3% (28/30) of the patients declined gradually over the 3-month study period, with a median decrease of 34.8% (IQR, 19.6-42.4%). NAb titers increased over time in parallel with the rise in immunoglobulin G (IgG) antibody levels, correlating well at week 3 (r = 0.41, P < .05). The NAb titers also demonstrated a significant positive correlation with levels of plasma proinflammatory cytokines, including stem cell factor (SCF), TNF-related apoptosis-inducing ligand (TRAIL), and macrophage colony-stimulating factor (M-CSF). CONCLUSIONS: These data provide useful information regarding dynamic changes in NAbs in patients with COVID-19 during the acute and convalescent phases.

Hepatitis B virus X protein modulates upregulation of DHX9 to promote viral DNA replication.

Hepatitis B virus (HBV) infection is a major cause of acute and chronic liver diseases. During the HBV life cycle, HBV hijacks various host factors to assist viral replication. In this research, we find that the HBV regulatory protein X (HBx) can induce the upregulation of DExH-box RNA helicase 9 (DHX9) expression by repressing proteasome-dependent degradation mediated by MDM2. Furthermore, we demonstrate that DHX9 contributes to viral DNA replication in dependence on its helicase activity and nuclear localization. In addition, the promotion of viral DNA replication by DHX9 is dependent on its interaction with Nup98. Our findings reveal that HBx-mediated DHX9 upregulation is essential for HBV DNA replication.