Ecophysiological responses of Phragmites australis populations to a tidal flat gradient in the Yangtze River Estuary, China.

Phragmites australis is a prevalent species in the Chongming Dongtan wetland and is capable of thriving in various tidal flat environments, including high salinity habitats. P. australis population displays inconsistent ecological performances, highlighting the need to uncover their survival strategies and mechanisms in tidal flats with diverse soil salinities. Upon comparing functional traits of P. australis at multiple tidal flats (low, middle, and high) and their responses to soil physicochemical properties, this study aimed to clarify the salt-tolerant strategy of P. australis and the corresponding mechanisms. These results showed that leaf characteristics, such as specific leaf area and leaf dry matter content, demonstrated more robust stability to soil salinity than shoot height and dry weight. Furthermore, as salt stress intensified, the activities of superoxide dismutase (SOD), catalase (CAT) and peroxisome (POD) in P. australis leaves at low tidal flat exhibited an increased upward trend compared to those at other tidal flats. The molecular mechanism of salt tolerance in Phragmites australis across various habitats was investigated using transcriptome sequencing. Weighted correlation network analysis (WGCNA) combined with differentially expressed genes (DEGs) screened out 3 modules closely related to high salt tolerance and identified 105 core genes crucial for high salt tolerance. Further research was carried out on the few degraded populations at low tidal flat, and 25 core genes were identified by combining WGCNA and DEGs. A decrease in the activity of ferroptosis marker gonyautoxin-4 and an increase in the content of Fe3+ in the degenerated group were observed, indicating that ferroptosis might participate in degradation. Furthermore, correlation analysis indicated a possible regulatory network between salt tolerance and ferroptosis. In short, this study provided new insights into the salt tolerance mechanism of P. australis population along tidal flats.

Corrosion Behavior of Homogenized and Extruded 1100 Aluminum Alloy in Acidic Salt Spray.

The 1100 aluminum alloy has been widely used in many industrial fields due to its high specific strength, fracture toughness, excellent thermal conductivity, and corrosion resistance. In this study, the corrosion behavior of the homogenized and hot-extruded 1100 aluminum alloy in acid salt spray environment for different time was studied. The microstructure of the 1100 aluminum alloy before and after corrosion was characterized by an optical microscope (OM), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and a laser scanning confocal microscope (LSCM). The difference in corrosion resistance between the homogenized and extruded 1100 aluminum alloy was analyzed via the electrochemical method. The results indicate that after hot extrusion at 400 °C, the microstructure of the 1100 aluminum alloy changes from an equiaxed crystal structure with (111) preferentially distributed in a fibrous structure with (220) preferentially distributed. There was no obvious dynamic recrystallization occurring during extrusion, and the second-phase particles containing Al-Fe-Si were coarse and unevenly distributed. With the increase in corrosion time, corrosion pits appeared on the surface of the 1100 aluminum alloy, and a corrosion product layer was formed on the surface of the homogenized 1100 aluminum alloy, which reduced the corrosion rate. After 96 h of corrosion, the CPR of the extruded samples was 0.619 mm/a, and that of the homogenized samples was 0.442 mm/a. The corrosion resistance of the extruded 1100 aluminum alloy was affected by the microstructure and the second phase, and no protective layer of corrosion products was formed on the surface, resulting in a faster corrosion rate and deeper corrosion pits.

Deletion of Nox from Listeria monocytogenes Strain EGDe Enhances Bacterial Virulence and Reduces the Production of Reactive Oxygen Species and Inflammatory Factors In Vivo.

The foodborne pathogens have a serious threat to human health, especially Listeria monocytogenes. NADPH oxidase (NOX) is involved in cellular respiration and the production of reactive oxygen species (ROS), acting as messengers to host cells during the infection. However, the role of nox in the process of L. monocytogenes infection is unclear. In this study, we examined the impact of nox in L. monocytogenes by gene deletion. The results of cell experiment showed that knocking out nox from L. monocytogenes strain EGDe resulted in a twofold increase invasion ability to Caco-2 cells compared with that of wild-type strain (WT), but did not affect adhesion ability. Animal infection assays also showed that bacterial loads in the liver and spleen of mice challenged with EGDe-Δnox were approximately two times higher compared with those challenged with the WT strain. On the one hand, quantitative real-time polymerase chain reaction revealed that deletion of nox leads to upregulation of genes related to the internalization of L. monocytogenes (inlA, inlB, and inlC). More importantly, the expression of listeriolysin-positive regulatory (prfA) gene increased by three times in vivo compared with that of WT. On the other hand, the deletion of nox resulted in a reduction of the upregulation of proinflammatory factors in EGDe-Δnox compared with the WT and complementary strains. Thus, our study revealed that nox affected the virulence of L. monocytogenes by upregulating the expression of virulence genes and regulating the production of ROS and inflammatory factors in vivo.

The spontaneously produced lysogenic prophage phi456 promotes bacterial resistance to adverse environments and enhances the colonization ability of avian pathogenic Escherichia coli strain DE456.

In the last decade, prophages that possess the ability of lysogenic transformation have become increasingly significant. Their transfer and subsequent activity in the host have a significant impact on the evolution of bacteria. Here, we investigate the role of prophage phi456 with high spontaneous induction in the bacterial genome of Avian pathogenic Escherichia coli (APEC) DE456. The phage particles, phi456, that were released from DE456 were isolated, purified, and sequenced. Additionally, phage particles were no longer observed either during normal growth or induced by nalidixic acid in DE456Δphi456. This indicated that the released phage particles from DE456 were only phi456. We demonstrated that phi456 contributed to biofilm formation through spontaneous induction of the accompanying increase in the eDNA content. The survival ability of DE456Δphi456 was decreased in avian macrophage HD11 under oxidative stress and acidic conditions. This is likely due to a decrease in the transcription levels of three crucial genes-rpoS, katE, and oxyR-which are needed to help the bacteria adapt to and survive in adverse environments. It has been observed through animal experiments that the presence of phi456 in the DE456 genome enhances colonization ability in vivo. Additionally, the number of type I fimbriae in DE456Δphi456 was observed to be reduced under transmission electron microscopy when compared to the wild-type strain. The qRT-PCR results indicated that the expression levels of the subunit of I fimbriae (fimA) and its apical adhesin (fimH) were significantly lower in DE456Δphi456. Therefore, it can be concluded that phi456 plays a crucial role in helping bacterial hosts survive in unfavorable conditions and enhancing the colonization ability in DE456.

Numerical simulation of single-jet impact cooling and double-jet impact cooling of hot-rolled L-shaped steel based on multiphase flow model.

In this paper, numerical simulations of single-jet impingement cooling and double-jet impingement cooling processes of heated L-shaped steel are carried out using the VOF model. The SIMPLEC pressure-velocity coupling algorithm and realizable k-ε model are used for the solution. The effects of jet position, water flow, and jet distance in the single-jet condition are analyzed in the simulations. The distributions of impact pressure, turbulence kinetic energy, and Nusselt number were obtained, as well as the variation of the peak values of these three factors with the jet position, water flow, and jet distance. The water flow rate is 3-11 L/min, and the jet distance is 5-25 cm. The effect of the distance between the two nozzles on the jet cooling uniformity under the dual jet condition was also analyzed. The distance between the two nozzles was 15-45 mm. The results showed that the variation of water flow rate had a greater effect on the ability of jet cooling compared with the jet position and jet distance, and the heat transfer efficiency also increased gradually with the increase of water flow, but the increased rate of heat transfer efficiency decreased gradually. When the flow rate increased from 3 to 11 L/min, the maximum instantaneous cooling rates at 1/4 of the thickness of the short side upper side, long side upper side, short side lower side, and long side lower side positions increased by 38.9%, 48.5%, 48.2%, and 32.9%, respectively. To ensure that the jet does not shift, the jet distance should be less than or equal to 10 cm. In the case of the double jet, the nozzle distance is 1.5 cm, and the cooling uniformity of the cooling area between the two nozzles is better. The peak Nusselt number in the cooling area of each part under the double jet cooling condition increased by 5%, 9.4%, 10.2%, and 13.3%, respectively, compared with the single jet.

PB-LKS: a python package for predicting phage-bacteria interaction through local K-mer strategy.

Bacteriophages can help the treatment of bacterial infections yet require in-silico models to deal with the great genetic diversity between phages and bacteria. Despite the tolerable prediction performance, the application scope of current approaches is limited to the prediction at the species level, which cannot accurately predict the relationship of phages across strain mutants. This has hindered the development of phage therapeutics based on the prediction of phage-bacteria relationships. In this paper, we present, PB-LKS, to predict the phage-bacteria interaction based on local K-mer strategy with higher performance and wider applicability. The utility of PB-LKS is rigorously validated through (i) large-scale historical screening, (ii) case study at the class level and (iii) in vitro simulation of bacterial antiphage resistance at the strain mutant level. The PB-LKS approach could outperform the current state-of-the-art methods and illustrate potential clinical utility in pre-optimized phage therapy design.

Phosphorylation of Arabidopsis UVR8 photoreceptor modulates protein interactions and responses to UV-B radiation.

Exposure of plants to ultraviolet-B (UV-B) radiation initiates transcriptional responses that modify metabolism, physiology and development to enhance viability in sunlight. Many of these regulatory responses to UV-B radiation are mediated by the photoreceptor UV RESISTANCE LOCUS 8 (UVR8). Following photoreception, UVR8 interacts directly with multiple proteins to regulate gene expression, but the mechanisms that control differential protein binding to initiate distinct responses are unknown. Here we show that UVR8 is phosphorylated at several sites and that UV-B stimulates phosphorylation at Serine 402. Site-directed mutagenesis to mimic Serine 402 phosphorylation promotes binding of UVR8 to REPRESSOR OF UV-B PHOTOMORPHOGENESIS (RUP) proteins, which negatively regulate UVR8 action. Complementation of the uvr8 mutant with phosphonull or phosphomimetic variants suggests that phosphorylation of Serine 402 modifies UVR8 activity and promotes flavonoid biosynthesis, a key UV-B-stimulated response that enhances plant protection and crop nutritional quality. This research provides a basis to understand how UVR8 interacts differentially with effector proteins to regulate plant responses to UV-B radiation.

Establishment and characterization of a recurrent malignant peripheral nerve sheath tumor cell line: RsNF.

Malignant peripheral nerve sheath tumor (MPNST) is a highly aggressive and recurrent soft tissue sarcoma. It most commonly occurs secondary to neurofibromatosis type I, and it has a 5-year survival rate of only 8-13%. To better study the tumor heterogeneity of MPNST and to develop diverse treatment options, more tumor-derived cell lines are needed to obtain richer biological information. Here, we established a primary cell line of relapsed MPNST RsNF cells derived from a patient diagnosed with NF1 and detected the presence of NF1 mutations and SUZ12 somatic mutations through whole-exome sequencing(WES). Through tumor molecular marker targeted sequencing and single-cell transcriptome sequencing, it was found that chromosome 7 copy number variation (CNV) was gained in this cell line, and ZNF804B, EGFR, etc., were overexpressed on chromosome 7. Therefore, RsNF cells can be used as a useful tool in NF1-associated MPNST genomic amplification studies and to develop new therapeutic strategies.

RNA-based modulation of macrophage-mediated efferocytosis potentiates antitumor immunity in colorectal cancer.

Tumor-associated macrophages play pivotal roles in tumor progression and metastasis. Macrophage-mediated clearance of apoptotic cells (efferocytosis) supports inflammation resolution, contributing to immune evasion in colorectal cancers. To reverse this immunosuppressive process, we propose a readily translatable RNA therapy to selectively inhibit macrophage-mediated efferocytosis in tumor microenvironment. A clinically approved lipid nanoparticle platform (LNP) is employed to encapsulate siRNA for the phagocytic receptor MerTK (siMerTK), enabling selective MerTK inhibition in the diseased organ. Decreased MerTK expression in tumor-associated macrophages results in apoptotic cell accumulation and immune activation in tumor microenvironment, leading to suppressed tumor growth and better survival in both liver and peritoneal metastasis models of colorectal cancers. siMerTK delivery combined with PD-1 blockade further produces enhanced antimetastatic efficacy with reactivated intratumoral immune milieu. Collectively, LNP-based siMerTK delivery combined with immune checkpoint therapy may present a feasible modality for metastatic colorectal cancer therapy.

Identification of a c-type heme oxygenase and its function during acclimation of cyanobacteria to nitrogen fluctuations.

The mechanisms of acclimating to a nitrogen-fluctuating environment are necessary for the survival of aquatic cyanobacteria in their natural habitats, but our understanding is still far from complete. Here, the synthesis of phycobiliprotein is confirmed to be much earlier than that of photosystem components during recovery from nitrogen chlorosis and an unknown protein Ssr1698 is discovered to be involved in this synthetic process. The unknown protein is further identified as a c-type heme oxygenase (cHO) in tetrapyrrole biosynthetic pathway and catalyzes the opening of heme ring to form biliverdin IXα, which is required for phycobilin production and ensuing phycobiliprotein synthesis. In addition, the cHO-dependent phycobiliprotein is found to be vital for the growth of cyanobacterial cells during chlorosis and regreening through its nitrogen-storage and light-harvesting functions, respectively. Collectively, the cHO expressed preferentially during recovery from nitrogen chlorosis is identified in photosynthetic organisms and the dual function of this enzyme-dependent phycobiliprotein is proposed to be an important mechanism for acclimation of aquatic cyanobacteria to a nitrogen-fluctuating environment.

Efficacy and safety of pembrolizumab with preoperative neoadjuvant chemotherapy in patients with resectable locally advanced head and neck squamous cell carcinomas.

Background: This study aimed to explore the efficacy and safety of pembrolizumab combined with chemotherapy as neoadjuvant therapy in patients with resectable locally advanced head and neck squamous cell carcinomas (LA-HNSCCs). Methods: In this prospective, single-arm, single-centre clinical trial, patients meeting the inclusion criteria were treated with preoperative neoadjuvant therapy with 200 mg pembrolizumab combined with 75 mg/m2 cisplatin and 175 mg/m2 paclitaxel. This was followed by surgery and postoperative adjuvant therapy. The primary endpoint was the postoperative pathological complete response (pCR) rate. All statistical analyses were performed using SPSS 26. Results: A total of 22 patients were enrolled. The location of primary lesion showed: hypopharynx were 15 (68.2%), oropharynx were 6 (27.3%) and oral cavity was 1 (4.5%). The postoperative pCR rate, was 36.4% (8/22), and there was no delay to surgery due to adverse drug reactions. The rate of laryngeal function preservation was 90.9% (20/22). Delayed wound healing was the main surgical complication, with an incidence of 22.7% (5/22). The median follow-up time was 9.5 months, and only 1 patient (4.55%) suffered a regional recurrence. Conclusion: Preoperative treatment with pembrolizumab and chemotherapy in resectable LA-HNSCC has a high pCR rate with no significant impact on surgical safety. This treatment was found to increase the rate of laryngeal function preservation. However, the effects of neoadjuvant immunotherapy on long-term prognosis in LA-HNSCCs require further study.

Successful anesthesia management with inhalation anesthesia in Rosai-Dorfman disease: a case report.

Rosai-Dorfman disease (RDD) is a rare, benign, non-Langerhans cell histiocytic proliferative disease. RDD with central nervous system involvement is extremely rare. Surgical excision is generally regarded as the appropriate treatment of choice for this disease, especially when the lesion causes neurological compression. RDD can be accompanied by systemic symptoms, such as malaise, fever, weight change, leukocytosis, anemia, and hormonal disturbance, which may be challenging during general management. Little is known regarding peri-anesthesia management of this rare disease. We report a case of a patient in his 20s who had recurrent RDD and had general anesthesia with perioperative management. He was obese and hepatic insufficiency. This case report adds to the literature regarding the perioperative anesthetic management of RDD with central nervous system involvement.

Hot Deformation Behavior and Processing Maps of an As-Cast Al-5Mg-3Zn-1Cu (wt%) Alloy.

One of the key issues limiting the application of Al-Mg-Zn-Cu alloys in the automotive industry is forming at a low cost. Isothermal uniaxial compression was accomplished in the range of 300-450 °C, 0.001-10 s-1 to study the hot deformation behavior of an as-cast Al-5.07Mg-3.01Zn-1.11Cu-0.01Ti alloy. Its rheological behavior presented characteristics of work-hardening followed by dynamic softening and its flow stress was accurately described by the proposed strain-compensated Arrhenius-type constitutive model. Three-dimensional processing maps were established. The instability was mainly concentrated in regions with high strain rates or low temperatures, with cracking being the main instability. A workable domain was determined as 385-450 °C, 0.001-0.26 s-1, in which dynamic recovery (DRV) and dynamic recrystallization (DRX) occurred. As the temperature rose, the dominant dynamic softening mechanism shifted from DRV to DRX. The DRX mechanisms transformed from continuous dynamic recrystallization (CDRX), discontinuous dynamic recrystallization (DDRX), and particle-stimulated nucleation (PSN) at 350 °C, 0.1 s-1 to CDRX and DDRX at 450 °C, 0.01 s-1, and eventually to DDRX at 450 °C, 0.001 s-1. The eutectic T-Mg32(AlZnCu)49 phase facilitated DRX nucleation and did not trigger instability in the workable domain. This work demonstrates that the workability of as-cast Al-Mg-Zn-Cu alloys with low Zn/Mg ratios is sufficient for hot forming.

Propagation of terahertz elastic longitudinal waves in piezoelectric semiconductor rods.

Terahertz elastic waves travelling in piezoelectric semiconductors (PSs) with the deformation-polarization-carrier coupling have a huge potential application in elastic wave-based devices. To reveal wave propagation characteristics of terahertz elastic waves in rod-like PS structures, we present three typical rod models based on the Hamilton principle and the linearization of the nonlinear current, which are extensions of the classical, Love, and Mindlin-Herrmann rod models for elastic media to those for PS materials. Using the derived equations, the analytical dispersion relations of the elastic longitudinal waves propagating in an n-type PS rod are obtained, which can be reduced to those for piezoelectric and elastic rods by sequentially dropping the corresponding electron- and piezoelectricity-related terms. The Mindlin-Herrmann rod model is more accurate for analysis of terahertz elastic longitudinal wave in rod-like PS structures. The effects of the interaction between the piezoelectricity and semiconducting properties on the dispersion behaviors of terahertz elastic longitudinal waves are investigated in detail. Numerical results show that both phase and group velocities have a 50%-60% reduction in the terahertz range in comparison with those in the low frequency range, and the effective tuning range of the initial electron concentration is different for longitudinal waves with different frequencies. It lays the theoretical foundations for the design of terahertz elastic wave-based devices.

Bispecific GPC3/PD­1 CAR­T cells for the treatment of HCC.

Constantly stimulated by the tumor microenvironment (TME), programmed death 1 (PD­1) is elevated, and it interacts with PD ligand 1 (PD­L1), rendering chimeric antigen receptor (CAR)­T cells dysfunctional. Hence, CAR­T cells immune to PD­1­induced immunosuppression were constructed to improve the function of CAR­T cells in hepatocellular carcinoma (HCC). Double­target CAR­T cells, targeting glypican­3 (GPC3) [a tumour-associated antigen (TAA)] and hindering PD­1­PD­L1 binding, were established. The expression of GPC3, PD­L1, and inhibitory receptors was measured using flow cytometry. The cytotoxicity, cytokine release, and differentiation level of CAR­T cells were determined using lactate dehydrogenase release assay, enzyme­linked immunosorbent assay, and flow cytometry, respectively. HCC cells were targeted and eliminated by double­target CAR­T cells. These double­target CAR­T cells limit PD­1­PD­L1 binding and sustain cytotoxicity to PD­L1+ HCC cells. The relatively low IR expression and differentiation level in double­target CAR­T cells in tumour tissues induced tumour­suppression and extended survival in PD­L1+ HCC TX models, as opposed to their single­target counterparts. The results of the present study suggested that the newly constructed double­target CAR­T cells exhibit stronger tumour­suppressing effects in HCC than their single­target counterparts, which are common, suggesting the potential of strengthening CAR­T cell activity in HCC treatment.

Histone Deacetylase 6 Inhibition Exploits Selective Metabolic Vulnerabilities in LKB1 Mutant, KRAS Driven NSCLC.

INTRODUCTION: In KRAS-mutant NSCLC, co-occurring alterations in LKB1 confer a negative prognosis compared with other mutations such as TP53. LKB1 is a tumor suppressor that coordinates several signaling pathways in response to energetic stress. Our recent work on pharmacologic and genetic inhibition of histone deacetylase 6 (HDAC6) revealed the impaired activity of numerous enzymes involved in glycolysis. On the basis of these previous findings, we explored the therapeutic window for HDAC6 inhibition in metabolically-active KRAS-mutant lung tumors. METHODS: Using cell lines derived from mouse autochthonous tumors bearing the KRAS/LKB1 (KL) and KRAS/TP53 mutant genotypes to control for confounding germline and somatic mutations in human models, we characterize the metabolic phenotypes at baseline and in response to HDAC6 inhibition. The impact of HDAC6 inhibition was measured on cancer cell growth in vitro and on tumor growth in vivo. RESULTS: Surprisingly, KL-mutant cells revealed reduced levels of redox-sensitive cofactors at baseline. This is associated with increased sensitivity to pharmacologic HDAC6 inhibition with ACY-1215 and blunted ability to increase compensatory metabolism and buffer oxidative stress. Seeking synergistic metabolic combination treatments, we found enhanced cell killing and antitumor efficacy with glutaminase inhibition in KL lung cancer models in vitro and in vivo. CONCLUSIONS: Exploring the differential metabolism of KL and KRAS/TP53-mutant NSCLC, we identified decreased metabolic reserve in KL-mutant tumors. HDAC6 inhibition exploited a therapeutic window in KL NSCLC on the basis of a diminished ability to compensate for impaired glycolysis, nominating a novel strategy for the treatment of KRAS-mutant NSCLC with co-occurring LKB1 mutations.

Assessment of Drug Susceptibility for Patient-Derived Tumor Models through Lactate Biosensing and Machine Learning.

A patient-derived tumor model (PDM) is a practical tool to rapidly screen chemotherapeutics for individual patients. The evaluation method of cell viability directly determines the application of PDMs for drug susceptibility testing. As one of the metabolites of "glycosis", the lactate content was used to evaluate cell viability, but these assays were not specific for tumor cells. Based on the "Warburg effect", wherein tumor cells preferentially rely on "aerobic glycolysis" to produce lactate instead of pyruvate in "anaerobic glycolysis" of normal cells, we reported a gold lactate sensor (GLS) to estimate the cell viability of PDMs in drug susceptibility testing. It demonstrated high consistency between the GLS and commercial cell viability assay. Unlike either imaging or cell viability assay, the GLS characterizes the cell viability, enables dynamic monitoring, and distinguishes tumor cells from other cells. Moreover, machine learning (ML) was employed to perform a multi-index assessment for drug susceptibility of PDMs, which proved to be accurate and practical for clinical application. Therefore, the GLS provides an ideal drug susceptibility testing tool for individualized medicine.