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BackgroundNAFLD (Nonalcoholic fatty liver disease) is becoming an increasingly common cause of chronic liver disease. Metabolic dysfunction, overweight/obesity, and diabetes are thought to be closely associated with increased NAFLD risk. However, few studies have focused on the mechanisms of NAFLD occurrence in T1DM.MethodsWe conducted a two-sample Mendelian randomization (MR) analysis to assess the causal association between T1DM and NAFLD with/without complications, such as coma, renal complications, ketoacidosis, neurological complications, and ophthalmic complications. Multiple Mendelian randomization methods, such as the inverse variance weighted (IVW) method, weighted median method, and MR-Egger test were performed to evaluate the causal association of T1DM and NAFLD using genome-wide association study summary data from different consortia, such as Finngen and UK biobank.ResultsWe selected 37 SNPs strongly associated with NAFLD/LFC (at a significance level of p < 5 × 10−8) as instrumental variables from the Finnish database based on the T1DM phenotype (8,967 cases and 308,373 controls). We also selected 14/16 SNPs based on with or without complications. The results suggest that the genetic susceptibility of T1DM does not increase the risk of NAFLD (OR=1.005 [0.99, 1.02], IVW p=0.516, MR Egger p=0.344, Weighted median p=0.959, Weighted mode p=0.791), regardless of whether complications are present. A slight causal effect of T1DM without complications on LFC was observed (OR=1.025 [1.00, 1.03], MR Egger p=0.045). However, none of the causal relationships were significant in the IVW (p=0.317), Weighted median (p=0.076), and Weighted mode (p=0.163) methods.ConclusionOur study did not find conclusive evidence for a causal association between T1DM and NAFLD, although clinical observations indicate increasing abnormal transaminase prevalence and NAFLD progression in T1DM patients.

The large yellow croaker Larimichthys crocea (Richardson, 1846) (Sciaenidae) is distributed in southern Yellow Sea, East China Sea, and northern South China Sea of China and is a commercially important nearshore fishery species. L. crocea was listed on the IUCN Red List as “Critically Endangered” in 2020 mainly due to the over-exploration of its spawning and over-wintering aggregations in the 1950s–1980s throughout its distribution region. However, detailed studies on reproductive dynamics of L. crocea were limited in the past three decades. In this study, the reproductive dynamics of L. crocea was examined in the traditional Guanjingyang (GJY) spawning ground, one of the 15 well-known ones in its distribution region. Samples were collected using set nets from April 2019 to November 2021 to ensure at least 20 samples for all 12 months. A total of 1,006 individuals were caught, ranging from 46 to 391 mm standard length (SL) and 1.45 to 1,110.05 g body weight (BW). A growth dimorphism was found between sexes with females heavier than males when body sizes exceeded 61 mm SL (non-parametric ANCOVA, p < 0.01). Gonad histology of all 1,006 individuals revealed, for the first time, that L. crocea was able to spawn almost year-round for both females and males. Two spawning peaks, spring and autumn, were identified in March and May and in November for females and in April to June and in October to November for males. The minimum sizes at sexual maturity were 160 mm SL for females and 112 mm SL for male. The sizes at 50% sexual maturity were 187.2 mm SL for females and 150.2 mm SL for males. Results showed that the minimum SL for female maturity decreased about 20% in the past six decades. The spawning peaks were 2 months earlier in spring and 1 month extension in autumn in GJY. Clearly, the national fishing moratorium regulation in May to August, an important fishery management measure in China, can only protect the spring spawning peak partly. Further evaluation on the influence of climate change on reproductive strategies and stock recruitment of L. crocea is highly recommended.

Sansha Bay (26.40−27.00°N, 119.50−120.20°E) is a typical semi-enclosed bay, located in northern Fujian Province, China, and adjacent to the East China Sea. The ichthyoplankton species composition and assemblage structure were investigated based on monthly sampling at 25 stations in April−September 2019, covering the important spring and summer spawning seasons in the region. Sampling was conducted in the first 3−5 days of the full moon or new moon phases using a standard plankton net through horizontal and vertical tows during daytime. In total, 25,819 ichthyoplankton samples were collected, of which 25,449 samples (i.e., 24,757 eggs and 692 larvae) were from horizontal tows. For horizontal tow samples, the ichthyoplankton were classified into 58 taxa in 15 orders and 23 families with a combination of external morphology and DNA barcoding analyses, from pelagic to demersal and benthic species. The dominant order was the Gobiiformes, including 23 species (39.7% of all species). The dominant taxa, in terms of relative abundance and frequency of occurrence, consisted of commercially important fishes, such as Setipinna tenuifilis (Valenciennes, 1848) (Engraulidae), Epinephelus akaara (Temminck and Schlegel, 1842) (Serraenidae), Collichthys lucidus (Richardson, 1844), Nibea albiflora (Richardson, 1846) (Sciaenidae), Acanthopagrus schlegelii (Bleeker, 1854), and Pagrus major (Temminck and Schlegel, 1843) (Sparidae), accounting for 78.9% of the horizontal tow samples. Low-valued and small-sized fishes, such as Stolephorus commersonnii Lacepède, 1803 (Engraulidae), Solea ovata Richardson, 1846 (Soleidae), Nuchequula nuchalis (Temminck and Schlegel, 1845), and Photopectoralis bindus (Valenciennes, 1835) (Leiognathidae), were also dominant species, accounting for 11.4% of the horizontal tow samples. The ichthyoplankton assemblage was categorized into five different temporal assemblages based on the cluster and nonmetric multidimensional scaling analysis, namely, April, May, June, July, and August−September (ANOSIM, Global R = 0.656, p < 0.01) with the highest density and richness of ichthyoplankton occurred in May. The spatial distribution pattern showed that the high density (ind./m3) of ichthyoplankton occurred mainly in S12–S25 in Guanjingyang and along the Dongchong Peninsula coastline into Dongwuyang, while low density occurred mainly in S01–S11 in the northwest waters of Sandu Island (ANOVA, F = 8.270, p < 0.05). Temperature, salinity, and chlorophyll a were key factors structuring the ichthyoplankton assemblages in Sansha Bay. In addition, this study revealed the changes of the ichthyoplankton composition, density, and spatial distribution in Sansha Bay over the past three decades.

Abstract Chimeric antigen receptor (CAR)‐positive cell therapy, specifically with anti‐CD19 CAR‐T (CAR19‐T) cells, achieves a high complete response during tumor treatment for hematological malignancies. Large‐scale production and application of CAR‐T therapy can be achieved by developing efficient and low‐cost enrichment methods for CAR‐T cells, expansion monitoring in vivo, and overcoming tumor escape. Here, novel CAR‐specific binding aptamers (CAR‐ap) to traceless sort CAR‐positive cells and obtain a high positive rate of CAR19‐T cells is identified. Additionally, CAR‐ap‐enriched CAR19‐T cells exhibit similar antitumor capacity as CAR‐ab (anti‐CAR antibody)‐enriched CAR‐T cells. Moreover, CAR‐ap accurately monitors the expansion of CAR19‐T cells in vivo and predicts the prognosis of CAR‐T treatment. Essentially, a novel class of stable CAR‐ap‐based bispecific circular aptamers (CAR‐bc‐ap) is constructed by linking CAR‐ap with a tumor surface antigen (TSA): protein tyrosine kinase 7 (PTK7) binding aptamer Sgc8. These CAR‐bc‐aps significantly enhance antitumor cytotoxicity with a loss of target antigens by retargeting CAR‐T cells to the tumor in vitro and in vivo. Overall, novel CAR‐aptamers are screened for traceless enrichment, monitoring of CAR‐positive cells, and overcoming tumor cell immune escape. This provides a low‐cost and high‐throughput approach for CAR‐positive cell‐based immunotherapy.

Background: The relationship between non-cholestatic liver disease and total bile acid (TBA) remains obscure. The present study aimed to verify this relationship in patients with non-cholestatic chronic hepatitis B virus (HBV) infection. Methods: A total of 922 consecutive chronic HBV infected patients with alkaline phosphatase (ALP) = 1.5 upper limit of normal (ULN) and gamma-glutamyl transferase (GGT) = 3 ULN were rigorously included in this crosssectional study. Liver biopsy was performed in 53 patients and Scheuer scoring system was used to evaluate inflammation grade. G3/G4 or Child-Pugh B/C were considered to be significant liver injury. Results: Compared to Child-Pugh A, TBA, total bilirubin (TBIL), ALP, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and AST to ALT ratio (AST/ALT) were significantly higher in Child-Pugh B/C, while TBIL to TBA ratio (TBIL/TBA) was significantly lower (all p < 0.001). In multivariate analysis, TBA and AST/ALT were independently correlated with Child-Pugh B/C [odds ratio (OR) = 1.04, p < 0.001; OR = 1.79, p < 0.001, respectively]. The area under the curve (AUC) of TBA (0.82) was significantly higher than that of AST (0.73, p < 0.001) and ALT (0.63, p < 0.001). Furthermore, in patients with liver biopsy, TBA was also significantly higher in G3/G4 while TBIL/TBA was significantly lower (p < 0.05). After adjusting the factors related to bile excretion, TBIL/TBA was independently associated with G3/G4 (OR = 0.89, p = 0.037). Conclusions: Serum TBA shows a close relationship with significant liver injury in chronic HBV infected patients without cholestasis. Assessment of TBA, especially in combination with TBIL/TBA, may serve as a non-invasive marker for the diagnosis of non-cholestatic hepatic damage. [ABSTRACT FROM AUTHOR]

Abstract Bacteria from coast seawaters are widely known to induce larval recruitment of many invertebrates. However, whether and how deep-sea bacteria, that play crucial roles in the ecological and biogeochemical cycles, promote larval recruitment remains little known. Here, the interaction between deep-sea bacterial biofilms (BFs) and Mytilus coruscus larvae was tested. All these nine deep-sea bacterial isolates triggered planktonic-sessile transition, and the highest percentage of post-larvae was observed in Virgibacillus sp. 1 BF. Except for Pseudomonas sp. 3, Pseudoalteromonas sp. 32 and Bacillus sp. 13, other BF cell densities were significantly related to their corresponding inductive efficiency. The deep-sea Virgibacillus sp. 1 BFʼs cue that triggers planktonic-sessile transition was uncovered. Treating Virgibacillus sp. 1 BFs through physic-chemical approaches reduced inducing impact and cell survival. The conditioned water collaborated with formalin-fixed Virgibacillus sp. 1 BF hoisted planktonic-sessile transition efficiency in comparison to each one alone. Thus, two signals derived from deep-sea bacteria trigger planktonic-sessile transition in M. coruscus. This finding firstly demonstrates that deep-sea bacteria has good potential for application in the mussel seed production and provides novel insight to clarify the bacteria-mussel interaction.

Summary: The bio-based lactic acid (LA) and the common metal ion chelating agent iminodiacetic acid (IDA) are used to design and prepare a polymeric sustained-release Pb2+ chelating agent by a brief one-step reaction. After the analysis on theoretical calculation for this reaction, poly(lactic acid-iminodiacetic acid) [P(LA-co-IDA)] with different monomer molar feed ratios is synthesized via direct melt polycondensation. P(LA-co-IDA) mainly has star-shaped structure, and some of them have two-core or three-core structure. Thus, a possible mechanism of the polymerization is proposed. The degradation rate of P(LA-co-IDA)s can reach 70% in 4 weeks. The change of IDA release rate is consistent with the trend of the degradation rate, and the good Pb2+ chelating performance is confirmed. P(LA-co-IDA) is expected to be developed as a lead poisoning treatment drug or Pb2+ adsorbent in the environment with long-lasting effect, and this research provides a new strategy for the development of such drugs.

B-cell acute lymphocytic leukemia (B-ALL) is a malignant blood cancer that develops in children and adults and leads to high mortality. THZ1, a covalent cyclin-dependent kinase 7 (CDK7) inhibitor, shows anti-tumor effects in various cancers by inhibiting cell proliferation and inducing apoptosis. However, whether THZ1 has an inhibitory effect on B-ALL cells and the underlying mechanism remains obscure. In this study, we showed that THZ1 arrested the cell cycle of B-ALL cells in vitro in a low concentration, while inducing the apoptosis of B-ALL cells in vitro in a high concentration by activating the apoptotic pathways. In addition, RNA-SEQ results revealed that THZ1 disrupted the cellular metabolic pathways of B-ALL cells. Moreover, THZ1 suppressed the cellular metabolism and blocked the production of cellular metabolic intermediates in B-ALL cells. Mechanistically, THZ1 inhibited the cellular metabolism of B-ALL by downregulating the expression of c-MYC-mediated metabolic enzymes. However, THZ1 treatment enhanced cell apoptosis in over-expressed c-MYC B-ALL cells, which was involved in the upregulation of p53 expression. Collectively, our data demonstrated that CDK7 inhibitor THZ1 induced the apoptosis of B-ALL cells by perturbing c-MYC-mediated cellular metabolism, thereby providing a novel treatment option for B-ALL.