ChRIPK1 caused necroptosis signaling pathway deficiency in Crassostrea hongkongensis.

RIPK1/TAK1 are important for programmed cell death, including liver death, necroptosis and apoptosis. However, there have been few published reports on the functions of RIPK1/TAK1 in invertebrates. In this study, full-length ChRIPK1 and ChTAK1 were cloned from C. hongkongensis through the rapid amplification of cDNA ends (RACE) technology. ChRIPK1 has almost no homology with human RIPK1 and lacks a kinase domain at the N-terminus but has a DD and RHIM domain. ChTAK1 is conserved throughout evolution. qRT‒PCR was used to analyze the mRNA expression patterns of ChRIPK1 in different tissues, developmental stages, and V. coralliilyticus-infected individuals, and both were highly expressed in the mantle and gills, while ChRIPK1 was upregulated in hemocytes and gills after V. coralliilyticus or S. aureus infection, which indicates that ChRIPK1 is involved in immune regulation. Fluorescence assays revealed that ChRIPK1 localized to the cytoplasm of HEK293T cells in a punctiform manner, but the colocalization of ChRIPK1 with ChTAK1 abolished the punctiform morphology. In the dual-luciferase reporter assay, both ChRIPK1 and ChRIPK1-RIHM activated the NF-κB signaling pathway in HEK293T cells, and ChTAK1 activated ChRIPK1 in the NF-κB signaling pathway. The apoptosis rate of the hemocytes was not affected by the necroptosis inhibitor Nec-1 but was significantly decreased, and ChRIPK1 expression was knocked down in the hemocytes of C. hongkongensis. These findings indicated that ChRIPK1 induces apoptosis but not necroptosis in oysters. This study provides a theoretical basis for further research on the molecular mechanism by which invertebrates regulate the programmed cell death of hemocytes in oysters.

A diabatization method based upon integrating the diabatic potential gradient difference.

In this work we develop a new scheme to construct a diabatic potential energy matrix (DPEM). We propose a diabatization method which is based on integrating the diabatic potential gradient difference to diabatize adiabatic ab initio energies. This method is capable of performing high-precision adiabatic-to-diabatic transformations, with a unique advantage in effectively handling the significant fluctuations in derivative-couplings caused by conical intersection (CI) seams. The above scheme is applied to the DPEM construction of the Na(3p) + H2 → NaH + H reaction. The fitting data including adiabatic energies, energy gradients and derivative-couplings obtained from a previous benchmark DPEM are diabatized and fitted using a general neural network fitting procedure to generate the DPEM. The produced DPEM can effectively describe nonadiabatic processes involving different electronic states. We further perform quantum dynamical calculations on the new DPEM and the previous benchmark DPEM, and the obtained results demonstrate the effectiveness of our scheme.

Efficient Method for Numerical Calculations of Molecular Vibrational Frequencies by Exploiting Sparseness of Hessian Matrix.

Molecular vibrational frequency analysis plays an important role in theoretical and computational chemistry. However, in many cases, the analytical frequencies are unavailable, whereas frequency calculations using conventional numerical methods are very expensive. In this work, we propose an efficient method to numerically calculate the frequencies. Our main strategies are to exploit the sparseness of the Hessian matrix and to construct the N-fold two-variable potential energy surfaces to fit the parabola parameters, which are later used for the construction of Hessian matrices. A set of benchmark calculations is performed for typical molecules of different sizes and complexities using the proposed method. The obtained frequencies are compared to those calculated with the analytical methods and conventional numerical methods. It is shown that the results yielded with the new method are in very good agreement with corresponding accurate values (with a maximum error of ∼20 cm-1), while the required computation resource is largely reduced compared to that required by conventional numerical methods. For medium-sized molecules, the calculational scaling is lowered to O(N1.6) (this work) from that of O(N2) (conventional numerical methods). For even larger molecules, more computational savings can be achieved, and the scaling is estimated to be quasilinear with respect to the molecular size.

Tanning wastewater restructured nitrogen-transforming bacteria communities and promoted N2O emissions in receiving river riparian sediments.

Physicochemical and toxicological characterization of leather tanning wastewater has been widely documented. However, few reports have examined the response of denitrification N2 and N2O emissions in riparian sediments of tannery wastewater-receiving rivers. In this study, 15N-nitrate labeling was used to reveal the effects of tanning wastewater on denitrification N2 and N2O emission in a wastewater-receiving river (the old Mang River, OMR). OMR riparian sediments were highly polluted with total organic carbon (93.39 mg/kg), total nitrogen (5.00 g/kg) and heavy metals; specifically, Cr, Zn, Cd, and Pb were found at concentrations 47.3, 5.8, 1.6, 4.3, and 2.8 times that in a nearby parallel river without tanning wastewater input (the new Mang River, NMR), respectively. The denitrification N2 emission rates (0.0015 nmol N · g-1 h-1) of OMR riparian sediments were significantly reduced by 2.5 times compared with those from the NMR (p < 0.05), but the N2O emission rates (0.31 nmol N · g-1 h-1) were significantly increased (4.1 times, p < 0.05). Although the dominant nitrogen-transforming bacteria phylum was Proteobacteria in the riparian sediments of both rivers, 11 nitrogen-transforming bacteria genera in the OMR were found to be significantly enriched; five of these were related to pollutant degradation based on linear discriminant analysis (LDA >3). The average activity of the electron transport system in the OMR was 6.3 times lower than that of the NMR (p < 0.05). Among pollution factors, heavy metal complex pollution was the dominant factor driving variations in N2O emissions, microbial community structure, and electron transport system activity. These results provide a new understanding and reference for the treatment of tanning wastewater-receiving rivers.

Magnolol promotes the autophagy of esophageal carcinoma cells by upregulating HACE1 gene expression.

Esophagus cancer (EC) is one of the most aggressive malignant digestive system tumors and has a high clinical incidence worldwide. Magnolol, a natural compound, has anticancer effects on many cancers, including esophageal carcinoma, but the underlying mechanism has not been fully elucidated. Here, we first find that magnolol inhibits the proliferation of esophageal carcinoma cells and enhances their autophagy activity in a dose- and time-dependent manner. This study demonstrates that magnolol increases the protein levels of LC3 II, accompanied by increased HACE1 protein levels in both esophageal carcinoma cells and xenograft tumors. HACE1-knockout (KO) cell lines are generated, and the ablation of HACE1 eliminates the anti-proliferative and autophagy-inducing effects of magnolol on esophageal carcinoma cells. Additionally, our results show that magnolol primarily promotes HACE1 expression at the transcriptional level. Therefore, this study shows that magnolol primarily exerts its antitumor effect by activating HACE1-OPTN axis-mediated autophagy. It can be considered a promising therapeutic drug for esophageal carcinoma.

Effects of polycyclic aromatic hydrocarbons on the gut-testis axis.

Polycyclic aromatic hydrocarbons (PAHs) are a large group of organic compounds which are comprised of two or more fused benzene rings. As a typical environmental pollutant, PAHs are widely distributed in water, soil, atmosphere and food. Despite extensive researches on the mechanisms of health damage caused by PAHs, especially their carcinogenic and mutagenic toxicity, there is still a lack of comprehensive summarization and synthesis regarding the mechanisms of PAHs on the gut-testis axis, which represents an intricate interplay between the gastrointestinal and reproductive systems. Thus, this review primarily focuses on the potential forms of interaction between PAHs and the gut microbiota and summarizes their adverse outcomes that may lead to gut microbiota dysbiosis, then compiles the possible mechanistic pathways on dysbiosis of the gut microbiota impairing the male reproductive function, in order to provide valuable insights for future research and guide further exploration into the intricate mechanisms underlying the impact of gut microbiota dysbiosis caused by PAHs on male reproductive function.

Perioperative Toripalimab Plus Chemotherapy for Patients With Resectable Non-Small Cell Lung Cancer: The Neotorch Randomized Clinical Trial.

Importance: Adjuvant and neoadjuvant immunotherapy have improved clinical outcomes for patients with early-stage non-small cell lung cancer (NSCLC). However, the optimal combination of checkpoint inhibition with chemotherapy remains unknown. Objective: To determine whether toripalimab in combination with platinum-based chemotherapy will improve event-free survival and major pathological response in patients with stage II or III resectable NSCLC compared with chemotherapy alone. Design, Setting, and Participants: This randomized clinical trial enrolled patients with stage II or III resectable NSCLC (without EGFR or ALK alterations for nonsquamous NSCLC) from March 12, 2020, to June 19, 2023, at 50 participating hospitals in China. The data cutoff date for this interim analysis was November 30, 2022. Interventions: Patients were randomized in a 1:1 ratio to receive 240 mg of toripalimab or placebo once every 3 weeks combined with platinum-based chemotherapy for 3 cycles before surgery and 1 cycle after surgery, followed by toripalimab only (240 mg) or placebo once every 3 weeks for up to 13 cycles. Main Outcomes and Measures: The primary outcomes were event-free survival (assessed by the investigators) and the major pathological response rate (assessed by blinded, independent pathological review). The secondary outcomes included the pathological complete response rate (assessed by blinded, independent pathological review) and adverse events. Results: Of the 501 patients randomized, 404 had stage III NSCLC (202 in the toripalimab + chemotherapy group and 202 in the placebo + chemotherapy group) and 97 had stage II NSCLC and were excluded from this interim analysis. The median age was 62 years (IQR, 56-65 years), 92% of patients were male, and the median follow-up was 18.3 months (IQR, 12.7-22.5 months). For the primary outcome of event-free survival, the median length was not estimable (95% CI, 24.4 months-not estimable) in the toripalimab group compared with 15.1 months (95% CI, 10.6-21.9 months) in the placebo group (hazard ratio, 0.40 [95% CI, 0.28-0.57], P < .001). The major pathological response rate (another primary outcome) was 48.5% (95% CI, 41.4%-55.6%) in the toripalimab group compared with 8.4% (95% CI, 5.0%-13.1%) in the placebo group (between-group difference, 40.2% [95% CI, 32.2%-48.1%], P < .001). The pathological complete response rate (secondary outcome) was 24.8% (95% CI, 19.0%-31.3%) in the toripalimab group compared with 1.0% (95% CI, 0.1%-3.5%) in the placebo group (between-group difference, 23.7% [95% CI, 17.6%-29.8%]). The incidence of immune-related adverse events occurred more frequently in the toripalimab group. No unexpected treatment-related toxic effects were identified. The incidence of grade 3 or higher adverse events, fatal adverse events, and adverse events leading to discontinuation of treatment were comparable between the groups. Conclusions and Relevance: The addition of toripalimab to perioperative chemotherapy led to a significant improvement in event-free survival for patients with resectable stage III NSCLC and this treatment strategy had a manageable safety profile. Trial Registration: ClinicalTrials.gov Identifier: NCT04158440.

A Testis-Specific DMRT1 (Double Sex and Mab-3-Related Transcription Factor 1) Plays a Role in Spermatogenesis and Gonadal Development in the Hermaphrodite Boring Giant Clam Tridacna crocea.

The testis-specific double sex and mab-3-related transcription factor 1 (DMRT1) has long been recognized as a crucial player in sex determination across vertebrates, and its essential role in gonadal development and the regulation of spermatogenesis is well established. Here, we report the cloning of the key spermatogenesis-related DMRT1 cDNA, named Tc-DMRT1, from the gonads of Tridacna crocea (T. crocea), with a molecular weight of 41.93 kDa and an isoelectric point of 7.83 (pI). Our hypothesis is that DMRT1 machinery governs spermatogenesis and regulates gonadogenesis. RNAi-mediated Tc-DMRT1 knockdown revealed its critical role in hindering spermatogenesis and reducing expression levels in boring giant clams. A histological analysis showed structural changes, with normal sperm cell counts in the control group (ds-EGFP) but significantly lower concentrations of sperm cells in the experimental group (ds-DMRT1). DMRT1 transcripts during embryogenesis exhibited a significantly high expression pattern (p < 0.05) during the early zygote stage, and whole-embryo in-situ hybridization confirmed its expression pattern throughout embryogenesis. A qRT-PCR analysis of various reproductive stages revealed an abundant expression of Tc-DMRT1 in the gonads during the male reproductive stage. In-situ hybridization showed tissue-specific expression of DMRT1, with a positive signal detected in male-stage gonadal tissues comprising sperm cells, while no signal was detected in other stages. Our study findings provide an initial understanding of the DMRT1 molecular machinery controlling spermatogenesis and its specificity in male-stage gonads of the key bivalve species, Tridacna crocea, and suggest that DMRT1 predominantly functions as a key regulator of spermatogenesis in giant clams.

[Retracted] LOXL1­AS1 promotes thymoma and thymic carcinoma progression by regulating miR­525­5p­HSPA9.

Following the publication of the above article, a concerned reader drew to the Editor's attention that certain of the cell invasion assay data featured in Figs. 2G and H, 5M and N, and 9K and L, and the tumor images shown in Fig. 6B, were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had either already been published elsewhere prior to the submission of this paper to Oncology Reports, or were under consideration for publication at around the same time (some of which have been retracted). In view of the fact that certain of these data had already apparently been published prior to the submission of this article for publication, the Editor of Oncology Reports has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 45: 117, 2021; DOI: 10.3892/or.2021.8068].

Polaron Formation in Conducting Polymers: A Novel Approach to Designing Materials with a Larger NLO Response.

Substantial efforts have been made to design and investigate new approaches for high-performance nonlinear optical (NLO) materials. Herein, we report polaron formation in conducting polymers as a new approach to designing materials with a large NLO response. A comparative study of polypyrrole and polypyrrole-based polaron (nPy+ where n = 1, 3, 5, 7, and 9) is carried out for optoelectronic and NLO properties. The studied polarons (PPy+) show excellent electronic properties and have reduced ionization potential (IP) as compared to neutral PPy, and a monotonic decrease is observed with increased chain lengths (1Py to 9Py). Interesting trends of global reactivity descriptors can be seen; the softness (S) increases with an increase in the chain length of PPy, while the hardness (η) decreases in the same fashion. The EH-L gaps for the PPy+ polaronic state are significantly lower than their corresponding neutral PPy. In the polaronic model (PPy+), radicals decisively reduce the crucial excitation energy, reminiscent of excess electrons (alkali metals). The performed TDOS spectral analysis further justifies the better conductive and electronic properties of polarons (PPy+) with increased chain lengths (conjugation). The static hyperpolarizability response (ßo) is recorded up to 1.3 × 102 au for 9Py, while for polaron 9Py+, it has increased up to 3.2 × 104 au. The static hyperpolarizability of the 9Py+ polaronic state is 246 times higher than that of the corresponding neutral analogue, 9Py. It is observed that the values of ßo obtained at the CAM-B3LYP/6-311+G(d,p) level of theory are comparable to those obtained at the LC-BLYP and ωB97XD functionals. The ßvec values show a strong correlation with the total hyperpolarizability (ßo). Furthermore, the calculated second harmonic generation (SHG) values are up to 4.0 × 106 au at 532 nm, whereas electro-optic Pockel's effect (EOPE) is much more pronounced at the smaller dispersion frequency (1064 nm). The TD-DFT study reveal the red-shifted absorption maxima (λmax) with an increased length of PPy+. A significant reduction in excitation energy (ΔE) is observed with increased length of PPy and PPy+, which also favors the improved NLO response. Hence, the studied thermally conducting polypyrrole-based polarons (PPy+) are new entries into NLO materials with better electrical and optical features.

The investigation of the interaction between fluorescent carbon dots labeling silk fibroin using a fluorescence microscope-surface plasmon resonance system.

The use of fluorescent carbon dots (CDs) as highly precise biolabeling probes has been widespread in the fields of live cell imaging and protein labeling due to their small size and excellent photoluminescence ability to accurately target specific molecules with surface chemical properties. However, there was a lack of research on the interaction between CDs and labeled molecules. In this work, we presented a novel investigation strategy, the fluorescence microscopy-surface plasmon resonance (FM-SPR) system, which combined the use of fluorescence microscopy and wavelength modulation surface plasmon resonance to study the interaction between CDs and labeled molecules in real-time. Using this system, simultaneously recorded the SPR signals and the fluorescence images on the surface of the FM-SPR sensor chip. We observed the dynamic curve and fluorescence images of the interaction between green emissive nitrogen-doped carbon dots (N-CDs) and silk fibroin (SF) in real-time. The kinetic parameters, the quantitative analysis, and the investigation of the binding could be achieved. The results showed a strong linear relationship between the change in SPR signals and the concentration of N-CDs, with a linear coefficient of 0.99913. The linear detection range was 2.5 µg/mL-100 µg/mL, and the real lowest detection limit reached 0.5 µg/mL. Additionally, the green fluorescence points in the imaging region on the FM-SPR sensor chip increased with the concentration of N-CDs, which was consistent with the change in SPR signals. Using this system we also acquired the association rate and dissociation rate of N-CDs to SF which were 2.65 × 10-5/s and 1.52 × 10-5/s, respectively. This demonstrated the effectiveness of our method in quantitatively analyzing SF labeled with N-CDs.

dwMLCS: An Efficient MLCS Algorithm based on Dynamic and Weighted Directed Acyclic Graph.

The problem of finding the longest common subsequence (MLCS) for multiple sequences is a computationally intensive and challenging problem that has significant applications in various fields such as text comparison, pattern recognition, and gene diagnosis. Currently, the dominant point-based MLCS algorithms have become popular and extensively studied. Generally, they construct the directed acyclic graph (DAG) of matching points and convert the MLCS problem into a search for the longest paths in the DAG. Several improvements have been made, focusing on decreasing model size and reducing redundant computations. These include 1) hash methods for eliminating duplicated nodes, 2) dynamic structures for supporting smaller DAG and 3) path pruning strategy and so on. However, the algorithms are still too limited when facing large-scale MLCS problem due to 1) the dynamic structures are too time-consuming to maintain and 2) the path pruning relies heavily on the tightness of the lower and upper bound of the MLCS. These factors contribute to the large-scale MLCS problem remaining a challenge. We propose a novel algorithm for the large-scale MLCS problem, named dwMLCS. It is based on two models: one is a dynamic DAG model which is both space and time efficient. It can decrease the size of the DAG significantly. The other is a weighted DAG model with new successor strategies. With this model, we design the algorithm for finding a tighter lower bound of the MLCS. Then, the path pruning is conducted to further reduce the size of the DAG and eliminate redundant computation. Additionally, we propose an upper bound method for improving the efficiency of the path pruning strategy. The experimental results demonstrate that the effectiveness and efficiency of the models and algorithms proposed are better than state-of-the-art algorithms. The source codes of dwMLCS can be downloaded from web site https://github.com/BioLab310/dwMLCS.

[Analysis of the efficacy of high tibial osteotomy combined with medial meniscus centralization in knee osteoarthritis].

OBJECTIVE: To explore the efficacy of high tibial osteotomy （HTO） combined with medial meniscus centralization in knee osteoarthritis. METHODS: A total of 26 patients who underwent surgery from October 2018 to October 2020 were reviewed. Among them, 14 patients underwent high tibial osteotomy combined with arthroscopic meniscus centralization surgery were centralized group, including 8 males and 6 females, with an average age of （50.2±1.4） years old and follow-up time of （16.8±4.0） months. Twelve patients with high tibial osteotomy were in the control group, including 6 males and 6 females, with an average age of （50.9±1.8） years and follow-up time of （19.0±4.8） months. Operation time, the knee Lysholm score, knee 2000 IKDC score, MRI, femoral tibial angle（FTA）, hip knee ankle angle （HKA）, and intraoperative and postoperative complications were recorded. RESULTS: All the incisions healed without any complication. The operation time in the centralized group was longer than that in the control group[（65.0±2.1）min vs（52.0±2.1）min, P<0.05]. The medial meniscus extrusion reduction value in the centralized group was significantly reduced compared with the control group[（2.8±1.4） mm vs （1.1±2.2） mm, P<0.05]. The FTA, HKA, knee Lyshlom score, and 2000 IKDC score between two groups were no significantly （P>0.05）. Postoperative knee Lyshlom score and knee 2000 IKDC score improved in both groups（P<0.05）. CONCLUSION: HTO combined with centralization of medial meniscus can improve the reduction of medial meniscus and improve knee function. The medium and long-term curative effect still needs long-term follow-up of more cases.

SLC2A1 boosts the resistance of non-small cell lung cancer to taxanes by stimulating the formation of EPCAM+ cancer stem-like cells via glycolysis.

BACKGROUND: The mechanisms by which SLC2A1 enhances chemo-resistance of taxanes to non-small cell lung cancer (NSCLC) remains enigmatic. METHODS: An investigation into the SLC2A1 expression pattern and prognosis across diverse datasets, as well as our internally collected samples, was undertaken. Additionally, the biological function of SLC2A1 was further delved into through in vitro experiments. The study also examined the chemo-resistance of NSCLC to taxanes using CCK-8, Annexin-V, and caspase-3 assays. Furthermore, the impact of taxanes on SLC2A1 expression was determined via western blot analysis. The effects of SLC2A1 on the formation of CSCs was examined via flow cytometry and metabolomics techniques. Finally, the impact of SLC2A1 on the tumor microenvironment was analyzed using single-cell sequencing and cellchat. RESULTS: In the present investigation, it was observed that there was an elevated expression of SLC2A1 in NSCLC tumor tissues, which exhibited a significant association with a poorer prognosis. SLC2A1 overexpression in vitro promoted NSCLC cell proliferation, invasion, migration, chemo-resistance, and the formation of CD90+ and EpCAM+ CSCs. NSCLC cells were categorized based on SLC2A1 and EpCAM expression. SLC2A1highEpCAM+ CSCs were more chemo-resistance to taxanes. NSCLC patients with high SLC2A1 and EpCAM expression had poorer prognosis. Mechanically, SLC2A1 promoted the formation of CD90+ and EpCAM+ CSCs via activating glycolysis. Finally, SLC2A1low tumor cells promoted CD8+T cell function via HLA-A, B, C, and suppressed NK cell function via HLA-E. CONCLUSION: Together, SLC2A1 plays an important role in enhancing chemo-resistance of taxanes to NSCLC.

Diffusion Barrier Performance of Ni-W Layer at Sn/Cu Interfacial Reaction.

As the integration of chips in 3D integrated circuits (ICs) increases and the size of micro-bumps reduces, issues with the reliability of service due to electromigration and thermomigration are becoming more prevalent. In the practical application of solder joints, an increase in the grain size of intermetallic compounds (IMCs) has been observed during the reflow process. This phenomenon results in an increased thickness of the IMC layer, accompanied by a proportional increase in the volume of the IMC layer within the joint. The brittle nature of IMC renders it susceptible to excessive growth in small-sized joints, which has the potential to negatively impact the reliability of the welded joint. It is therefore of the utmost importance to regulate the formation and growth of IMCs. The following paper presents the electrodeposition of a Ni-W layer on a Cu substrate, forming a barrier layer. Subsequently, the barrier properties between the Sn/Cu reactive couples were subjected to a comprehensive and systematic investigation. The study indicates that the Ni-W layer has the capacity to impede the diffusion of Sn atoms into Cu. Furthermore, the Ni-W layer is a viable diffusion barrier at the Sn/Cu interface. The "bright layer" Ni2WSn4 can be observed in all Ni-W coatings during the soldering reflow process, and its growth was almost linear. The structure of the Ni-W layer is such that it reduces the barrier properties that would otherwise be inherent to it. This is due to the "bright layer" Ni2WSn4 that covers the original Ni-W barrier layer. At a temperature of 300 °C for a duration of 600 s, the Ni-W barrier layer loses its blocking function. Once the "bright layer" Ni2WSn4 has completely covered the original Ni-W barrier layer, the diffusion activation energy for Sn diffusion into the Cu substrate side will be significantly reduced, particularly in areas where the distortion energy is concentrated due to electroplating tension. Both the "bright layer" Ni2WSn4 and Sn will grow rapidly, with the formation of Cu-Sn intermetallic compounds (IMCs). At temperatures of 250 °C, the growth of Ni3Sn4-based IMCs is controlled by grain boundaries. Conversely, the growth of the Ni2WSn4 layer (consumption of Ni-W layer) is influenced by a combination of grain boundary diffusion and bulk diffusion. At temperatures of 275 °C and 300 °C, the growth of Ni3Sn4-based IMCs and the Ni2WSn4 layer (consumption of Ni-W layer) are both controlled by grain boundaries. The findings of this study can inform the theoretical design of solder joints with barrier layers as well as the selection of Ni-W diffusion barrier layers for use in different soldering processes. This can, in turn, enhance the reliability of microelectronic devices, offering significant theoretical and practical value.

Resistance of an intertidal oyster(Saccostrea mordax)to marine heatwaves and the implication for reef building.

Marine heatwaves (MHWs) have a significant impact on intertidal bivalves and the ecosystems they sustain, causing the destruction of organisms' original habitats. Saccostrea mordax mainly inhabits the intertidal zone around the equator, exhibiting potential tolerance to high temperatures and maybe a species suitable for habitat restoration. However, an understanding about the tolerance mechanism of S. mordax to high temperatures is unclear. It is also unknown the extent to which S. mordax can tolerate repeated heatwaves of increasing intensity and frequency. Here, we simulated the effects of two scenarios of MHWs and measured the physiological and biochemical responses and gene expression spectrum of S. mordax. The predicted responses varied greatly across heatwaves, and no heatwave had a significant impact on the survival of S. mordax. Specifically, there were no statistically significant changes apparent in the standard metabolic rate and the activities of enzymes of the oyster during repeated heatwaves. S. mordax exposed to high-intensity heatwaves enhanced their standard metabolic rate to fuel essential physiological maintenance and increasing activity of SOD and expression of HSP70/90. These strategies are presumably at the expense of functions related to immunity and growth, as best exemplified by significant depressions in activities of enzymes (NaK, CaMg, T-ATP, and AKP) and expression levels of genes (Rab, eEF-2, HMGR, Rac1, SGK, Rab8, etc.). The performance status of S. mordax tends to improve by implementing a suite of less energy-costly compensatory mechanisms at various levels of biological organization when re-exposed to heatwaves. The adaptive abilities shown by S. mordax indicate that they can play a crucial role in the restoration of oyster reefs in tropical seas.

Identification and validation of prognostic and immunotherapeutic responses in esophageal squamous carcinoma based on hypoxia phenotype-related genes.

The study aimed to investigate the clinical significance of the interaction between hypoxia and the immune system in esophageal squamous cell carcinoma (ESCC) microenvironment. A comprehensive evaluation of 13 hypoxia phenotype-related genes (HPRs) was conducted using data from TCGA-ESCC and two GEO cohorts. Three distinct HPRclusters were identified, and the HPRscore was established as an independent prognostic factor (p = 0.001), with higher scores indicating poorer prognosis. The HPRscore was validated in various immunotherapy cohorts, demonstrating its efficacy in evaluating immunotherapy and chemotherapy outcomes. Additionally, phenome-wide association study (PheWAS) analysis showed that PKP1 had no significant correlation with other traits at the gene level. PKP1 was identified as a potential prognostic marker for ESCC, with upregulated expression observed in ESCC patients. In vitro experiments showed that the knockdown of PKP1 inhibited ESCC cell proliferation and migration. These findings suggest that the novel HPRscore and PKP1 may serve as prognostic tools and therapeutic targets for ESCC patients.

A novel disulfidptosis-related prognostic gene signature and experimental validation identify ACTN4 as a novel therapeutic target in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is a prevalent form of malignancy globally. Disulfidptosis is novel programmed cell death pathway based on disulfide proteins, may have a positive impact on the development of LUAD treatment strategies. OBJECTIVE: To investigate the impact of disulfidptosis-related genes (DRGs) on the prognosis of LUAD, developed a risk model to facilitate the diagnosis and prognostication of patients. We also explored ACTN4 (DRGs) as a new therapeutic biomarker for LUAD. METHODS: We investigated the expression patterns of DRGs in both LUAD and noncancerous tissues. To assess the prognostic value of the DRGs, we developed risk models through univariate Cox analysis and lasso regression. The expression and function of ACTN4 was evaluated by qRT-PCR, immunohistochemistry and in vitro experiments. The TIMER examined the association between ACTN4 expression and immune infiltration in LUAD. RESULTS: Ten differentially expressed DRGs were identified. And ACTN4 was identified as potential risk factors through univariate Cox regression analysis (P< 0.05). ACTN4 expression and riskscore were used to construct a risk model to predict overall survival in LUAD, and high-risk demonstrated a significantly higher mortality rate compared to the low-risk cohort. qRT-PCR and immunohistochemistry assays indicated ACTN4 was upregulated in LUAD, and the upregulation was associated with clinicopathologic features. In vitro experiments showed the knockdown of ACTN4 expression inhibited the proliferation in LUAD cells. The TIMER analysis demonstrated a correlation between the expression of ACTN4 and the infiltration of diverse immune cells. Elevated ACTN4 expression was associated with a reduction in memory B cell count. Additionally, the ACTN4 expression was associated with m6A modification genes. CONCLUSIONS: Our study introduced a prognostic model based on DRGs, which could forecast the prognosis of patients with LUAD. The biomarker ACTN4 exhibits promise for the diagnosis and management of LUAD, given its correlation with tumor immune infiltration and m6A modification.

Chromosome-level genome assembly and annotation of rare and endangered tropical bivalve, Tridacna crocea.

Tridacna crocea is an ecologically important marine bivalve inhabiting tropical coral reef waters. High quality and available genomic resources will help us understand the population structure and genetic diversity of giant clams. This study reports a high-quality chromosome-scale T. crocea genome sequence of 1.30 Gb, with a scaffold N50 and contig N50 of 56.38 Mb and 1.29 Mb, respectively, which was assembled by combining PacBio long reads and Hi-C sequencing data. Repetitive sequences cover 71.60% of the total length, and a total of 25,440 protein-coding genes were annotated. A total of 1,963 non-coding RNA (ncRNA) were determined in the T. crocea genome, including 62 micro RNA (miRNA), 58 small nuclear RNA (snRNA), 83 ribosomal RNA (rRNA), and 1,760 transfer RNA (tRNA). Phylogenetic analysis revealed that giant clams diverged from oyster about 505.7 Mya during the evolution of bivalves. The genome assembly presented here provides valuable genomic resources to enhance our understanding of the genetic diversity and population structure of giant clams.

How many people can the Qinghai-Tibet Plateau hold, and how large cities can be built in recent hundred years?

The Qinghai-Tibet Plateau (QTP) serves as a vital barrier for both national security and ecological preservation. Overpopulation and urban sprawl pose threats to its ecological security, while underpopulation and small urban cities also undermine national security. Hence, optimizing population distribution and urban development on the QTP is crucial for bolstering the national security perimeter and ensuring basic modernisation across China. Nonetheless, understanding the population carrying capacity (CC) of the QTP and how large cities can safeguard both national security and ecological stability remains limited. To address this research gap, we utilised various model algorithms and methodologies to assess the population CC and urban scale of the QTP from seven different perspectives. The results indicate that the permanent population CC of the QTP in 2050 will be 26.2 million people, with an urbanisation level of 57.25 %, thereby allowing 15 million people to enter cities. Thus, the QTP can add 13.07 million people to its permanent population in the future, with a newly added urban population of 8.75 million, increasing the urbanisation level by 9.67 %. The future permanent population will mainly be distributed in the Xining, Lhasa, and Qaidam metropolitan areas. Combined, the permanent and urban populations will account for 38.54 % and 49.84 % of the QTP, respectively. Moreover, these populations will be moderately dispersed in 11 important node cities and more widely dispersed in key border towns. These findings provide a scientific basis for the sustainable development and high-quality urbanisation of the QTP, which have important implications for achieving sustainable development goals, offering crucial references for governments to formulate resource management policies and achieve sustainable resource utilisation.