Cancer SLC6A6-mediated taurine uptake transactivates immune checkpoint genes and induces exhaustion in CD8+ T cells.

Taurine is used to bolster immunity, but its effects on antitumor immunity are unclear. Here, we report that cancer-related taurine consumption causes T cell exhaustion and tumor progression. The taurine transporter SLC6A6 is correlated with aggressiveness and poor outcomes in multiple cancers. SLC6A6-mediated taurine uptake promotes the malignant behaviors of tumor cells but also increases the survival and effector function of CD8+ T cells. Tumor cells outcompete CD8+ T cells for taurine by overexpressing SLC6A6, which induces T cell death and malfunction, thereby fueling tumor progression. Mechanistically, taurine deficiency in CD8+ T cells increases ER stress, promoting ATF4 transcription in a PERK-JAK1-STAT3 signaling-dependent manner. Increased ATF4 transactivates multiple immune checkpoint genes and induces T cell exhaustion. In gastric cancer, we identify a chemotherapy-induced SP1-SLC6A6 regulatory axis. Our findings suggest that tumoral-SLC6A6-mediated taurine deficiency promotes immune evasion and that taurine supplementation reinvigorates exhausted CD8+ T cells and increases the efficacy of cancer therapies.

miR-107 reverses the multidrug resistance of gastric cancer by targeting the CGA/EGFR/GATA2 positive feedback circuit.

Chemotherapy is still the main therapeutic strategy for gastric cancer (GC). However, most patients eventually acquire multidrug resistance (MDR). Hyperactivation of the EGFR signaling pathway contributes to MDR by promoting cancer cell proliferation and inhibiting apoptosis. We previously identified the secreted protein CGA as a novel ligand of EGFR and revealed a CGA/EGFR/GATA2 positive feedback circuit that confers MDR in GC. Herein, we outline a microRNA-based treatment approach for MDR reversal that targets both CGA and GATA2. We observed increased expression of CGA and GATA2 and increased activation of EGFR in GC samples. Bioinformatic analysis revealed that miR-107 could simultaneously target CGA and GATA2, and the low expression of miR-107 was correlated with poor prognosis in GC patients. The direct interactions between miR-107 and CGA or GATA2 were validated by luciferase reporter assays and Western blot analysis. Overexpression of miR-107 in MDR GC cells increased their susceptibility to chemotherapeutic agents, including fluorouracil, adriamycin, and vincristine, in vitro. Notably, intratumor injection of the miR-107 prodrug enhanced MDR xenograft sensitivity to chemotherapies in vivo. Molecularly, targeting CGA and GATA2 with miR-107 inhibited EGFR downstream signaling, as evidenced by the reduced phosphorylation of ERK and AKT. These results suggest that miR-107 may contribute to the development of a promising therapeutic approach for the treatment of MDR in GC.

The role of HPV11 E7 in modulating STING-dependent interferon ß response in recurrent respiratory papillomatosis.

Recurrent respiratory papillomatosis (RRP) is a rare benign tumor caused mainly by the infection of the respiratory tract epithelial cells by the human papillomavirus (HPV) type 6/11. However, the specific mechanisms underlying the inhibition of the host's innate immune response by HPV remain unclear. For this purpose, we employed single-cell RNA sequencing to analyze the states of various immune cells in RRP samples post-HPV infection and utilized a cellular model of HPV infection to elucidate the mechanisms by which HPV evades the innate immune system in RRP. The results revealed distinct immune cell heterogeneity in RRP and demonstrated that HPV11 E7 can inhibit the phosphorylation of the stimulator of interferon genes protein, thereby circumventing the body's antiviral response. In vitro co-culture experiments demonstrated that stimulation of macrophages to produce interferon-beta induced the death of HPV-infected epithelial cells, also reducing HPV viral levels. In summary, our study preliminarily identifies the potential mechanisms by which HPV evades the host's antiviral immune response, as well as the latent antiviral functions exhibited by activated macrophages. This research serves as an initial exploration of antiviral immune evasion in RRP, laying a solid foundation for investigating immunotherapeutic approaches for the disease.IMPORTANCESurgical tumor reduction is the most common treatment for recurrent respiratory papillomatosis (RRP). One of the characteristics of RRP is its persistent recurrence, and multiple surgeries are usually required to control the symptoms. Recently, some adjuvant therapies have shown effectiveness, but none of them can completely clear human papillomavirus (HPV) infection, and thus, a localized antiviral immune response is significant for disease control; after all, HPV infection is limited to the epithelium. Inhibition of interferon-beta (IFN-ß) secretion by HPV11 E7 viral proteins in epithelial cells by affecting stimulator of interferon genes phosphorylation may account for the persistence of low-risk HPV replication in the RRP. Moreover, suppression of the IFN-I pathway in RRP cell types might provide clues regarding the hyporeactive function of local immune cells. However, activation of macrophage groups to produce IFN-ß can still destroy HPV-infected cells.

A novel lncRNA associated with the prognosis of patients with colorectal cancer resists apoptosis through the LYN/BCL-2 pathway.

PURPOSE: We found a novel lncRNA named lncAC138150.2 related to the overall survival and staging of patients with colorectal cancer (CRC) by bioinformatic analysis using data from the Cancer Genome Atlas (TCGA), and the study aimed to elucidate the function of lncAC138150.2 and underlying mechanisms. METHODS: Target molecules were knocked down by transfection with antisense oligonucleotides (ASOs), siRNAs, or lentiviruses and overexpressed by transfection with plasmids. The function of lncAC138150.2 was determined using histological, cytological, and molecular biology methods. The underlying mechanism of lncAC138150.2 function was investigated using RNA-seq, bioinformatics analysis, and molecular biology methods. RESULTS: The expression of lncAC138150.2 was increased in colorectal tissues compared with paired normal tissues. The lncAC138150.2 knockdown increased apoptosis but did not change the cell proliferation, cell cycle distribution, or cell migration ability of CRC cells, while lncAC138150.2 overexpression decreased CRC apoptosis. lncAC138150.2 was mainly located in the cell nucleus, and each lncAC138150.2 transcript knockdown increased CRC apoptosis. BCL-2 pathway was significantly altered in apoptosis induced by lncAC138150.2 knockdown, which was alleviated by BAX knockdown. The expression of LYN was significantly decreased with lncAC138150.2 knockdown, LYN knockdown increased CRC apoptosis, and its overexpression completely alleviated CRC apoptosis induced by lncAC138150.2 knockdown. CONCLUSION: lncAC138150.2 significantly inhibited CRC apoptosis and affected the prognosis of patients with CRC, through the LYN/BCL-2 pathway.

Roles of alcohol dehydrogenase 1 in the biological activities of Candida albicans.

Candida albicans stands as the foremost prevalent human commensal pathogen and a significant contributor to nosocomial fungal infections. In the metabolism of C. albicans, alcohol dehydrogenase 1 (Adh1) is one of the important enzymes that converts acetaldehyde produced by pyruvate decarboxylation into ethanol at the end of glycolysis. Leveraging the foundational processes of alcoholic fermentation, Adh1 plays an active role in multiple biological phenomena, including biofilm formation, interactions between different species, the development of drug resistance, and the potential initiation of gastrointestinal cancer. Additionally, Adh1 within C. albicans has demonstrated associations with regulating the cell cycle, stress responses, and various intracellular states. Furthermore, Adh1 is extracellularly localized on the cell wall surface, where it plays roles in processes such as tissue invasion and host immune responses. Drawing from an analysis of ADH1 gene structure, expression patterns, and fundamental functions, this review elucidates the intricate connections between Adh1 and various biological processes within C. albicans, underscoring its potential implications for the prevention, diagnosis, and treatment of candidiasis.

Fully Automated Identification of Lymph Node Metastases and Lymphovascular Invasion in Endometrial Cancer From Multi-Parametric MRI by Deep Learning.

BACKGROUND: Early and accurate identification of lymphatic node metastasis (LNM) and lymphatic vascular space invasion (LVSI) for endometrial cancer (EC) patients is important for treatment design, but difficult on multi-parametric MRI (mpMRI) images. PURPOSE: To develop a deep learning (DL) model to simultaneously identify of LNM and LVSI of EC from mpMRI images. STUDY TYPE: Retrospective. POPULATION: Six hundred twenty-one patients with histologically proven EC from two institutions, including 111 LNM-positive and 168 LVSI-positive, divided into training, internal, and external test cohorts of 398, 169, and 54 patients, respectively. FIELD STRENGTH/SEQUENCE: T2-weighted imaging (T2WI), contrast-enhanced T1WI (CE-T1WI), and diffusion-weighted imaging (DWI) were scanned with turbo spin-echo, gradient-echo, and two-dimensional echo-planar sequences, using either a 1.5 T or 3 T system. ASSESSMENT: EC lesions were manually delineated on T2WI by two radiologists and used to train an nnU-Net model for automatic segmentation. A multi-task DL model was developed to simultaneously identify LNM and LVSI positive status using the segmented EC lesion regions and T2WI, CE-T1WI, and DWI images as inputs. The performance of the model for LNM-positive diagnosis was compared with those of three radiologists in the external test cohort. STATISTICAL TESTS: Dice similarity coefficient (DSC) was used to evaluate segmentation results. Receiver Operating Characteristic (ROC) analysis was used to assess the performance of LNM and LVSI status identification. P value <0.05 was considered significant. RESULTS: EC lesion segmentation model achieved mean DSC values of 0.700 ± 0.25 and 0.693 ± 0.21 in the internal and external test cohorts, respectively. For LNM positive/LVSI positive identification, the proposed model achieved AUC values of 0.895/0.848, 0.806/0.795, and 0.804/0.728 in the training, internal, and external test cohorts, respectively, and better than those of three radiologists (AUC = 0.770/0.648/0.674). DATA CONCLUSION: The proposed model has potential to help clinicians to identify LNM and LVSI status of EC patients and improve treatment planning. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Microbially Induced Soil Colloidal Phosphorus Mobilization Under Anoxic Conditions.

Understanding the behavior of colloidal phosphorus (Pcoll) under anoxic conditions is pivotal for addressing soil phosphorus (P) mobilization and transport and its impact on nutrient cycling. Our study investigated Pcoll dynamics in acidic floodplain soil during a 30-day flooding event. The sudden oxic-to-anoxic shift led to a significant rise in pore-water Pcoll levels, which exceeded soluble P levels by more than 2.7-fold. Colloidal fractions transitioned from dispersed forms (<220 nm) to colloid-associated microaggregates (>220 nm), as confirmed by electron microscopy. The observed increase in colloidal sizes was paralleled by their heightened ability to form aggregates. Compared to sterile control conditions, anoxia prompted the transformation of initially dispersed colloids into larger particles through microbial activity. Curiously, the 16S rRNA and ITS microbial diversity analysis indicated that fungi were more strongly associated with anoxia-induced colloidal release than bacteria. These microbially induced shifts in Pcoll lead to its higher mobility and transport, with direct implications for P release from soil into floodwaters.

The impact of chemical properties of the solid-liquid-adsorbate interfaces on the entropy-enthalpy compensation involved in adsorption.

Despite extensive studies on the thermodynamic mechanism governing molecular adsorption at the solid-water interface, a comprehensive understanding of the crucial role of interface properties in mediating the entropy-enthalpy compensation during adsorption is lacking, particularly at a quantitative level. Herein, we employed two types of surface models (hydroxyapatite and graphene) along with a series of amino acids to successfully elucidate how distinct interfacial features dictate the delicate balance between entropy and enthalpy variations. The adsorption of all amino acids on the hydroxyapatite surface is an enthalpy-dominated process, where the water-induced enthalpic component of the free energy and the surface-adsorbate electrostatic interaction term alternatively act as the driving force for adsorption in different regions of the surface. Although favorable interactions are observed between amino acids and the graphene surface, the entropy-enthalpy compensation exhibits dependence on the molecular size of the adsorbates. For small amino acids, favorable enthalpy changes predominantly determine their adsorption behavior; however, larger amino acids tend to bind more tightly with the graphene surface, which is thermodynamically dominated by the entropy variations despite the structural characteristics of amino acids. This study reveals specific entropy-enthalpy mechanisms underlying amino acid adsorption at the solid-liquid interface, providing guidance for surface design and synthesis of new biomolecules.

Effectiveness of surgery combined with photodynamic therapy for recurrent respiratory papillomatosis.

OBJECTIVE: This study aims to analyze the safety and effectiveness of a new model of surgery combined with Photodynamic therapy for treating Recurrent Respiratory Papillomatosis (RRP). METHODS: Review the case data of patients with RRP who opted for comprehensive surgery combined with Photodynamic therapy at the Nanjing BenQ Medical Center, from January 2021 to May 2023. The efficacy of this program was evaluated by comparing the annual number of surgeries and Derkay scores before and after the surgery. RESULTS: A total of 23 RRP patients were included in the study. After treatment, the recurrence rate was 65.2 % (15/23), with an average recurrence time of 94.3 ± 50.8 days. The average Derkay score at the time of recurrence was significantly lower than the average pre-treatment Derkay score (P < 0.001). The average annual recurrence rate before treatment was 2.2 ± 1.3, compared to 1.5 ± 1.5 after treatment, with no significant difference (P = 0.16). However, subgroup analysis revealed a significant decrease in the annual recurrence rate of adult-onset RRP after treatment (P = 0.01). The most common adverse reaction was mild pharyngeal pain (11/23). There were 3 cases of new-onset vocal cord adhesions. No patients experienced serious respiratory-related adverse reactions, anesthesia-related adverse reactions, or systemic phototoxic reactions. CONCLUSION: In conclusion, this study indicates that surgery combined with Photodynamic therapy (PDT) might be a safe and effective option for treating RRP, especially in patients with Adult-Onset Recurrent Respiratory Papillomatosis (AORRP).

Risk factors for cardio-cerebrovascular events among patients undergoing continuous ambulatory peritoneal dialysis and their association with serum magnesium.

Serum magnesium levels exceeding 0.9 mmol/L are associated with increased survival rates in patients with CKD. This retrospective study aimed to identify risk factors for cardio-cerebrovascular events among patients receiving continuous ambulatory peritoneal dialysis (CAPD) and to examine their correlations with serum magnesium levels. Sociodemographic data, clinical physiological and biochemical indexes, and cardio-cerebrovascular event data were collected from 189 patients undergoing CAPD. Risk factors associated with cardio-cerebrovascular events were identified by univariate binary logistic regression analysis. Correlations between the risk factors and serum magnesium levels were determined by correlation analysis. Univariate regression analysis identified age, C-reactive protein (CRP), red cell volume distribution width standard deviation, red cell volume distribution width corpuscular volume, serum albumin, serum potassium, serum sodium, serum chlorine, serum magnesium, and serum uric acid as risk factors for cardio-cerebrovascular events. Among them, serum magnesium ≤0.8 mmol/L had the highest odds ratio (3.996). Multivariate regression analysis revealed that serum magnesium was an independent risk factor, while serum UA (<440 µmol/L) was an independent protective factor for cardio-cerebrovascular events. The incidence of cardio-cerebrovascular events differed significantly among patients with different grades of serum magnesium (χ2 = 12.023, p = 0.002), with the highest incidence observed in patients with a serum magnesium concentration <0.8 mmol/L. High serum magnesium levels were correlated with high levels of serum albumin (r = 0.399, p < 0.001), serum potassium (r = 0.423, p < 0.001), and serum uric acid (r = 0.411, p < 0.001), and low levels of CRP (r = -0.279, p < 0.001). In conclusion, low serum magnesium may predict cardio-cerebrovascular events in patients receiving CAPD.

Biotransformation and metabolite activity analysis of flavonoids from propolis in vivo.

Propolis is a natural resinous compound produced by bees, mixed with their saliva and wax, and has a range of biological benefits, including antioxidant and anti-inflammatory effects. This article reviews the in vivo transformation of propolis flavonoids and their potential influence on drug efficacy. Despite propolis is widely used, there is little research on how the active ingredients of propolis change in the body and how they interact with drugs. Future research will focus on these interactions and the metabolic fate of propolis in vivo.

UV irradiation enhanced removal of colloidal phosphorus in agricultural runoff.

Colloidal phosphorus (P) is an important P form in agricultural runoff and can threaten water quality. However, up to date, there are few effective approaches to mitigate colloidal P pollution. This study investigated the effect of ultraviolet (UV) irradiation on medium-colloidal (MC; 220 nm-450 nm) and fine-colloidal (FC; 3 kDa-220 nm) P in agricultural runoff. Under 24 h of UV irradiation, as the most abundant colloidal P fraction, concentration of total P (TP) in FC consistently decreased by 81.0%, while TP concentration in MC first increased by 74.4% after 3 h and then decreased with irradiation time. At the same time, particulate TP (>450 nm) concentration was found to be increased from 0 to 14.7 µM. However, there were no obvious variations in TP concentrations in FC and MC fractions under dark conditions. In FC fraction, with the decrease of TP, the corresponding concentrations of iron (Fe), aluminum (Al), silicon (Si) declined synchronously, and ferric iron/ferrous iron (Fe(III)/Fe(II)) ratio and organic matter (OM) concentration were reduced as well. These results suggested that P in FC fraction was gradually transformed into particulate P during photoreduction of Fe(III) and photodegradation of OM under UV irradiation. Our study helps to understand the mechanism of the phototransformation of colloidal P, and propose an UV irradiation-based approach to remove colloidal P in agricultural runoff.

Recurrence and malignant transformation of laryngeal leukoplakia treated with CO2 laser: A systematic review and meta-analysis.

BACKGROUND: Laryngeal leukoplakia (LL) is a white lesion with high potential of recurrence and malignant transformation. Currently, CO2 laser has become the primary surgical treatment for LL, and the recurrence and malignant transformation rates after treatment vary widely. OBJECTIVE: We performed a systematic review and meta-analysis dedicated to evaluating the rates of recurrence and malignant transformation of LL lesions treated with CO2 laser and exploring relevant risk factors for recurrence or malignant transformation. METHODS: Literature searches were conducted on ProQuest, PubMed, Web of Science, Ovid Medline, Embase, and Cochrane databases. Some articles identified through hand searching were included. RESULTS: A total of 14 articles and 1462 patients were included in this review. Pooled results showed that the overall recurrence rate was 15%, and the malignant transformation rate was 3%. Subgroup analysis showed that the dysplasia grade was not a significant risk factor for the recurrence and malignant transformation of LL (P > .05). CONCLUSIONS: The results of this systematic review and meta-analysis suggest that the CO2 laser is a safe and effective surgical instrument for the excision of LL, which yields low rates of recurrence and malignant transformation. The risk factors relevant to recurrence or malignant transformation remain unclear and require further investigation.

Performance of an integrated sediment interceptor in removing phosphorus from agricultural drainage water.

Reducing phosphorus (P) loss from agricultural drainage water is challenging. In this study, we aimed to remove P from agricultural drainage water by developing an integrated sediment interceptor with adsorbent modules filled with Zr/Zn nanocomposite-modified ceramsite (ZMC-interceptor). The results of sequential chemical extraction and 31P NMR showed that the contents of H2O-P (1.15 % of total P), NaHCO3-Pi (10.48 % of total P), and ortho-P (orthophosphate, 90.6 % of total P) in the sediments of the ZMC-interceptors were higher than those in nearby field soils. The average enrichment ratios of particulate P (PP, >450 nm), medium-colloidal P (MCP, 220-450 nm), fine-colloidal P (FCP, 1-220 nm), and truly dissolved P (Truly DP, <1 nm) in the sediment over the field soil were 1.37, 1.21, 1.70, and 3.01, respectively. No significant differences were found in the sediment P-trapping function with and without ZMC integrated sediment interceptors. However, the ZMC-interceptors remarkably reduced total P (39.7 % for influent concentrations of 0.19-0.68 mg L-1) from agricultural drainage water compared to those unmodified ceramsite-interceptors (21.7 % for influent concentrations of 0.17-0.66 mg L-1) during the drainage 'window period' (June-August 2022). This was mainly due to the higher removal efficacies of MCP (19.7 %), FCP (23.3 %), and Truly DP (34.8 %) of the ZMC-interceptors. This study highlighted that the ZMC-interceptor not only trapped P in the sediment but also facilitated the removal of different-sized P fractionated from agricultural drainage water.

Nobiletin Stimulates Adrenal Hormones and Modulates the Circadian Clock in Mice.

Polymethoxyflavonoids, such as nobiletin (abundant in Citrus depressa), have been reported to have antioxidant, anti-inflammatory, anticancer, and anti-dementia effects, and are also a circadian clock modulator through retinoic acid receptor-related orphan receptor (ROR) α/γ. However, the optimal timing of nobiletin intake has not yet been determined. Here, we explored the time-dependent treatment effects of nobiletin and a possible novel mechanistic idea for nobiletin-induced circadian clock regulation in mice. In vivo imaging showed that the PER2::LUC rhythm in the peripheral organs was altered in accordance with the timing of nobiletin administration (100 mg/kg). Administration at ZT4 (middle of the light period) caused an advance in the peripheral clock, whereas administration at ZT16 (middle of the dark period) caused an increase in amplitude. In addition, the intraperitoneal injection of nobiletin significantly and potently stimulated corticosterone and adrenaline secretion and caused an increase in Per1 expression in the peripheral tissues. Nobiletin inhibited phosphodiesterase (PDE) 4A1A, 4B1, and 10A2. Nobiletin or rolipram (PDE4 inhibitor) injection, but not SR1078 (RORα/γ agonist), caused acute Per1 expression in the peripheral tissues. Thus, the present study demonstrated a novel function of nobiletin and the regulation of the peripheral circadian clock.

MRI Plain Scan: A Tool in the Management of Cervical Cancer during Pregnancy.

OBJECTIVE: The purpose of this study was to assess the diagnostic value of magnetic resonance imaging (MRI) in staging and treatment of cervical cancer in pregnancy, and to evaluate the benefit of apparent diffusion coefficient (ADC) during neoadjuvant chemotherapy management. MATERIALS AND METHODS: This was a retrospective cohort study. Patients were divided into two groups according to the stage of cervical cancer. The mean term of pregnancy at the time of the diagnosis was the early second trimester (range 10-27 weeks) and the median age was 33 years (range 26-40 years). The abdominal and pelvic MRI images and clinical data of these patients were reviewed. Tumor size, local tumor spread, and nodal involvement were evaluated using an MRI dataset. The treatment and follow-up imaging were analyzed as well, and the ADC was measured before and after the chemotherapy. RESULTS: 16 patients with histopathologically confirmed cervical cancer during pregnancy were retrospectively enrolled. 7 patients were diagnosed with local cervical cancer (FIGO stage IAI) and designated as early stage group, as the lesion was invisible on MRI. In this group, pregnancies were allowed to continue until cesarean delivery (CD) at 38-41 weeks. The other 9 patients presenting with local or extensive cervical cancer (FIGO stage IB2-IIA2) were designated as the advanced-stage group. The lesion could be measured and analyzed on MRI. They were treated with neoadjuvant chemotherapy in pregnancy. Among them, 6 patients underwent TP regimen (paclitaxel 135~175 mg/m2 plus cisplatin 70~75 mg/m2), while 3 patients received TC regimen (paclitaxel 135~175 mg/m2 plus carboplatin AUC=5). NACT was performed for 1 to 2 courses before surgery. ADC demonstrated significant differences before and after chemotherapy administered during pregnancy (1.06 ± 0.12 sec/mm2 vs. 1.34 ± 0.21 sec/mm2). CONCLUSION: MRI has been found to be helpful in staging cervical cancer in pregnancy. Patients with stage IA confirmed by MRI can choose conservative treatment and continue the pregnancy until term birth. MRI can dynamically monitor the efficacy of chemotherapy for patients with stage IB and above during pregnancy. ADC value can have a potential role in the evaluation of chemotherapy efficacy.

Effects of Cr Addition on the Microstructure and Mechanical Properties of an Al-Si-Cu-Mg Alloy.

The effects of chromium (Cr) addition ranging 0.1-0.3 wt.% on the microstructure and mechanical properties of Al-7Si-4Cu-0.25Mg (wt.%) alloy have been investigated. The cast Cr-free alloy consisted of α-Al, eutectic Si, Q-Al5Mg8Cu2Si6 and θ-Al2Cu phases. Doping of Cr resulted in the appearance of a polyhedron-shaped α-Al13Cr4Si4 phase with a cubic structure. The Al13Cr4Si4 particles were found to embed with Al2Cu blocks and bring about size reduction for the Al2Cu blocks. The area fraction of Al13Cr4Si4 monotonously increased with Cr content. After T6 treatment, the Al2Cu blocks almost fully dissolved and transformed to θ'-Al2Cu precipitates in the Cr-containing alloys. TEM observation revealed relatively large-sized θ' precipitates attached to Al13Cr4Si4 dispersoids. The Cr-containing alloys showed impressive mechanical properties, with the peak strength up to 452 MPa at room temperature. The ductility exhibited an increasing trend with Cr content, but the strength dropped dramatically when the Cr content reached 0.3 wt.%. It is suggested that the strength contribution from the Al13Cr4Si4 phase is limited, especially at an elevated temperature.

Progress in clinical diagnosis and treatment of colorectal cancer with rare genetic variants.

Targeted therapy is crucial for advanced colorectal cancer (CRC) positive for genetic drivers. With advances in deep sequencing technology and new targeted drugs, existing standard molecular pathological detection systems and therapeutic strategies can no longer meet the requirements for careful management of patients with advanced CRC. Thus, rare genetic variations require diagnosis and targeted therapy in clinical practice. Rare gene mutations, amplifications, and rearrangements are usually associated with poor prognosis and poor response to conventional therapy. This review summarizes the clinical diagnosis and treatment of rare genetic variations, in genes including erb-b2 receptor tyrosine kinase 2 (ERBB2), B-Raf proto-oncogene, serine/threonine kinase (BRAF), ALK receptor tyrosine kinase/ROS proto-oncogene 1, receptor tyrosine kinase (ALK/ROS1), neurotrophic receptor tyrosine kinases (NTRKs), ret proto-oncogene (RET), fibroblast growth factor receptor 2 (FGFR2), and epidermal growth factor receptor (EGFR), to enhance understanding and identify more accurate personalized treatments for patients with rare genetic variations.

Evolutionary radiation strategy revealed in the Scarabaeidae with evidence of continuous spatiotemporal morphology and phylogenesis.

Evolutionary biology faces the important challenge of determining how to interpret the relationship between selection pressures and evolutionary radiation. The lack of morphological evidence on cross-species research adds to difficulty of this challenge. We proposed a new paradigm for evaluating the evolution of branches through changes in characters on continuous spatiotemporal scales, for better interpreting the impact of biotic/abiotic drivers on the evolutionary radiation. It reveals a causal link between morphological changes and selective pressures: consistent deformation signals for all tested characters on timeline, which provided strong support for the evolutionary hypothesis of relationship between scarabs and biotic/abiotic drivers; the evolutionary strategies under niche differentiation, which were manifested in the responsiveness degree of functional morphological characters with different selection pressure. This morphological information-driven integrative approach sheds light on the mechanism of macroevolution under different selection pressures and is applicable to more biodiversity research.

The Microscopic Morphology of Mouthparts and Their Sensilla in the Mycophagous Ladybeetle Illeis chinensis (Coleoptera: Coccinellidae).

The morphological diversity of insect mouthparts is closely related to changes in food sources and diets. Research into the structures of insect mouthparts may help to establish a fundamental basis for a better understanding of insect feeding mechanisms. In this study, we examined the fine morphology of the mouthparts of Illeis chinensis using scanning electron microscopy. We paid particular attention to the types, quantities, and distribution of sensilla on the mouthparts. Our results showed that the basic components of the mouthparts of I. chinensis are the same as those in other lady beetles, i.e., the labrum, mandible, maxillae, labium, and hypopharynx. We also found structural specialization indicating adaptation to fungal feeding. On the mouthparts, there are eight kinds of sensilla and two kinds of glandular structures, including sensilla chaetica, sensilla basiconica, sensilla styloconica, sensilla coeloconica, sensilla campaniformia, sensilla placodea, sensilla digitiformia, Böhm bristles, perforated plates, and cuticular pores. This is the first time that sensilla digitiformia has been reported in ladybirds. Finally, variations in mouthparts among ladybirds with differing diets, as well as the putative functions of each of the mouthparts and sensilla, were discussed. This research can provide a reference for understanding the functions of the mouthparts in ladybird feeding behavior and thereby contribute to the development of precise insect behavior regulation and management strategies.