Cadmium causes cerebral mitochondrial dysfunction through regulating mitochondrial HSF1.

Mitochondria, as the powerhouse of the cell, play a vital role in maintaining cellular energy homeostasis and are known to be a primary target of cadmium (Cd) toxicity. The improper targeting of proteins to mitochondria can compromise the normal functions of the mitochondria. However, the precise mechanism by which protein localization contributes to the development of mitochondrial dysfunction induced by Cd is still not fully understood. For this research, Hy-Line white variety chicks (1-day-old) were used and equally distributed into 4 groups: the Control group (fed with a basic diet), the Cd35 group (basic diet with 35 mg/kg CdCl2), the Cd70 group (basic diet with 70 mg/kg CdCl2) and the Cd140 group (basic diet with 140 mg/kg CdCl2), respectively for 90 days. It was found that Cd caused the accumulation of heat shock factor 1 (HSF1) in the mitochondria, and the overexpression of HSF1 in the mitochondria led to mitochondrial dysfunction and neuronal damage. This process is due to the mitochondrial HSF1 (mtHSF1), causing mitochondrial fission through the upregulation of dynamin-related protein 1 (Drp1) content, while inhibiting oligomer formation of single-stranded DNA-binding protein 1 (SSBP1), resulting in the mitochondrial DNA (mtDNA) deletion. The findings unveil an unforeseen role of HSF1 in triggering mitochondrial dysfunction.

Deliberation concerning the role of M1-type macrophage subset in oral carcinogenesis.

Over the last decade, accumulating evidence has suggested that tumor-associated macrophages (TAMs) play a significant role in the tumor development. This commentary wishes to highlight the findings by You, et al. that M1-like TAMs could cascade a mesenchymal/stem-like phenotype of oral squamous cell carcinoma (OSCC) via the IL6/Stat3/THBS1 feedback loop. These unprecedented findings identified M1-like TAMs-regulated processes as potentially tumor-promotion in the context of OSCC immunomicroenvironment.

The Medial Prefrontal Cortex-Basolateral Amygdala Circuit Mediates Anxiety in Shank3 InsG3680 Knock-in Mice.

Anxiety disorder is a major symptom of autism spectrum disorder (ASD) with a comorbidity rate of ~40%. However, the neural mechanisms of the emergence of anxiety in ASD remain unclear. In our study, we found that hyperactivity of basolateral amygdala (BLA) pyramidal neurons (PNs) in Shank3 InsG3680 knock-in (InsG3680+/+) mice is involved in the development of anxiety. Electrophysiological results also showed increased excitatory input and decreased inhibitory input in BLA PNs. Chemogenetic inhibition of the excitability of PNs in the BLA rescued the anxiety phenotype of InsG3680+/+ mice. Further study found that the diminished control of the BLA by medial prefrontal cortex (mPFC) and optogenetic activation of the mPFC-BLA pathway also had a rescue effect, which increased the feedforward inhibition of the BLA. Taken together, our results suggest that hyperactivity of the BLA and alteration of the mPFC-BLA circuitry are involved in anxiety in InsG3680+/+ mice.

Genomic analysis of Alteromonas sp. M12 isolated from the Mariana Trench reveals its role in dimethylsulfoniopropionate cycling.

Dimethylsulfoniopropionate (DMSP) is a ubiquitous organosulfur molecule in marine environments with important roles in stress tolerance, global carbon and sulfur cycling, and chemotaxis. It is the main precursor of the climate active gas dimethyl sulfide (DMS), which is the greatest natural source of bio­sulfur transferred from ocean to atmosphere. Alteromonas sp. M12, a Gram-negative and aerobic bacterium, was isolated from the seawater samples collected from the Mariana Trench at the depth of 2500 m. Here, we report the complete genome sequence of strain M12 and its genomic characteristics to import and utilize DMSP. The genome of strain M12 contains one circular chromosome (5,012,782 bp) with the GC content of 40.88%. Alteromonas sp. M12 can grow with DMSP as a sole carbon source, and produced DMS with DMSP as a precursor. Genomic analysis showed that strain M12 contained a set of genes involved in the downstream steps of DMSP cleavage, but no known genes encoding DMSP transporters or DMSP lyases. The results indicated that this strain contained novel DMSP transport and cleavage genes in its genome which warrants further investigation. The import of DMSP into cells may be a strategy of strain M12 to adapt the hydrostatic pressure environment in the Mariana Trench, as DMSP can be used as a hydrostatic pressure protectant. This study sheds light on the catabolism of DMSP by deep-sea bacteria.

Realm of hepatitis E: Challenges and opportunities.

Hepatitis E virus (HEV), responsible for widespread viral hepatitis, infects approximately 2.3 billion individuals globally, with a significant mortality burden in Asia. The virus, primarily transmitted through contaminated water and undercooked meat, is often underdiagnosed, particularly in immunocompromised patients. Current HEV treatments, while effective, are limited by adverse effects, necessitating research into safer alternatives. Moreover, HEV's extrahepatic manifestations, impacting the nervous and renal systems, remain poorly understood. This study underscores the imperative for enhanced HEV research, improved diagnostic methods, and more effective treatments, coupled with increased public health awareness and preventive strategies.

[Response of Relationship Between Microplastic Abundance and Nitrogen Metabolism Function Microorganisms and Genes in Water].

The impact of microplastics (MPs) as a new type of pollutant on water pollution has become a research hotspot. To explore the response relationship between the abundance of MPs and nitrogen metabolism function in a freshwater environment, Lake Ulansuhai was used as the research object; the abundance of MPs in the water was detected using a Zeiss microscope, and the distribution characteristics of nitrogen metabolism functional bacteria and functional genes in the water were analyzed using metagenomics sequencing. The correlation analysis method was used to explore the relationship between the abundance of MPs and nitrogen metabolism functional microorganisms and nitrogen metabolism functional genes. The results showed that the presence of MPs in freshwater environments had a higher impact on Cyanobacteria and Firmicutes as the dominant phyla, and the presence of MPs promoted their enrichment and growth. Among the dominant bacterial genera, MPs promoted the growth of Mycobacterium and inhibited Candidatus_Planktopila more significantly, further indicating that in freshwater environments, MPs affected normal nitrogen metabolism by affecting microbial communities, and pathways such as carbon and nitrogen fixation and denitrification were important pathways for MPs to affect nitrogen metabolism. From the perspective of nitrogen metabolism functional genes, it was found that the abundance of MPs significantly affected some functional genes during nitrification (pmoA-amoA, pmoB-amoB, and pmoC-amoC), denitrification (nirK and napA), and dissimilatory nitrate reduction (nrfA) processes (P < 0.05). Moreover, the influence of MPs abundance on different functional genes in the same pathway of nitrogen metabolism varied, making the impact of MPs on aquatic environments very complex; thus, its harm to the water environment cannot be underestimated.

Chondromyxoid fibroma of the temporomandibular joint - a rare case.

BACKGROUND: Chondromyxoid fibroma (CMF) is a rare cartilaginous tumor, accounting for < 1% of benign bone tumors. We report a case of temporomandibular joint (TMJ)-CMF, involving the pterygopalatine space and skull base and discuss its epidemiology, clinical characteristics, and management. CASE PRESENTATION: A 56-year-old woman presented with facial asymmetry and progressive mouth opening restriction due to a mass expanding upwardly to the auriculotemporal region. Using digital techniques to determine the lesion's boundary and reconstruct the normal glenoid fossa, the temporalis myofascial flap was transplanted between the titanium mesh and condyle to reconstruct the disc after tumor resection. CONCLUSION: This case highlights the importance of identifying patients with TMJ-CMF.

Biomechanism of abnormal stress on promoting osteoarthritis of temporomandibular joint through Piezo1 ion channel.

OBJECTIVE: This study aimed to investigate whether flow fluid shear stress (FFSS)-mediated signal transduction affects the function of Piezo1 ion channel in chondrocyte and to further explore the role of mechanical overloading in development of temporomandibular joint osteoarthritis (TMJ OA). METHODS: Immunohistochemical staining was used to determine the expression of Piezo1 in TMJ OA tissue collected from rat unilateral anterior crossbite (UAC) models. Chondrocytes harvested from normal adult SD rats were treated with FFSS (0, 4, 8, 12 dyn/cm2) in vitro. Immunofluorescent staining, real-time polymerase chain reaction, western blotting, flow cytometry and phalloidin assay were performed to detect the changes of cellular morphology as well as the expression of Piezo1 and certain pro-inflammatory and degradative factors in chondrocyte. RESULTS: Immunohistochemical analysis revealed that significantly increased Piezo1 expression was associated with UAC stimulation (p < .05). As applied FFSS escalated (4, 8 and 12 dyn/cm2), the expression levels of Piezo1, ADAMTS-5, MMP-13 and Col-X gradually increased, compared with the non-FFSS group (p < .05). Administering Piezo1 ion channel inhibitor to chondrocytes beforehand, it was observed that expression of ADAMTS-5, MMP-13 and Col-X was substantially decreased following FFSS treatment (p < .05) and the effect of cytoskeletal thinning was counteracted. The activated Piezo1 ion channel enhanced intracellular Ca2+ excess in chondrocytes during abnormal mechanical stimulation and the increased intracellular Ca2+ thinned the cytoskeleton of F-actin. CONCLUSIONS: Mechanical overloading activates Piezo1 ion channel to promote pro-inflammation and degradation and to increase Ca2+ concentration in chondrocyte, which may eventually result in TMJ OA.

Nano­selenium alleviates cadmium-induced blood-brain barrier destruction by restoring the Wnt7A/ß-catenin pathway.

Selenium (Se), a highly beneficial animal feed additive, exhibits remarkable antioxidant and anti-inflammatory properties. Nano­selenium (Nano-Se) is an advanced formulation of Se featuring a specialized drug delivery vehicle, with good bioavailability, higher efficacy, and lower toxicity compared to the traditional form of Se. With the advancement of industry, cadmium (Cd) contamination occurs in different countries and regions and thereby contaminating different food crops, and the degree of pollution is degree increasing year by year. The present investigation entailed the oral administration of CdCl2 and/or Nano-Se to male chickens of the Hy-Line Variety White breed, which are one day old, subsequent to a 7-day adaptive feeding period, for a duration of 90 days. The study aimed to elucidate the potential protective impact of Nano-Se on Cd exposure. The study found that Nano-Se demonstrates potential in mitigating the blood-brain barrier (BBB) dysfunction characterized by impairment of adherens junctions (AJS) and tight junctions (TJS) by inhibiting reactive oxygen species (ROS) overproduction. In addition, the data uncovered that Nano-Se demonstrates a proficient ability in alleviating BBB impairment and inflammatory reactions caused by Cd through the modulation of the Wnt7A/ß-catenin pathway, highlights its potential to maintain brain homeostasis. Hence, this research anticipates that the utilization of Nano-Se effectively mitigate the detrimental impacts associated with Cd exposure on the BBB.

The FAK/occludin/ZO-1 complex is critical for cadmium-induced testicular damage by disruption of the integrity of the blood-testis barrier in chickens.

Cadmium (Cd) is a well-known testis toxicant. The blood-testis barrier (BTB) is a crucial component of the testis. Cd can disrupt the integrity of the BTB and reproductive function. However, the mechanism of Cd-induced disruption of BTB and testicular damage has not been fully elucidated. Here, our study investigates the effects of Cd on BTB integrity and testicular dysfunction. 80 (aged 1 day) Hy-Line white variety chickens were randomly designed into 4 groups and treated for 90 days, as follows: control group (essential diet), 35 Cd, 70 Cd and 140 Cd groups (35, 70 and 140 mg/kg Cd). The results found that Cd exposure diminished volume of the testes and induced histopathological lesions in the testes. Exposure to Cd induced an inflammatory response, disrupted the structure and function of the FAK/occludin/ZO-1 protein complex and disrupted the tight junction and adherens junction in the BTB. In addition, Cd exposure reduced the expression of steroid-related proteins and inhibited testosterone synthesis. Taken together, these data elucidate that Cd disrupts the integrity of the BTB and further inhibits spermatogenesis by dissociating the FAK/occludin/ZO-1 complex, which provides a basis for further investigation into the mechanisms of Cd-induced impairment of male reproductive function and pharmacological protection.

Nerve block reduces the incidence of 3-year postoperative mortality: a retrospective cohort study.

Purpose: A retrospective cohort study was performed to determine the effect of nerve block on the incidence of postoperative mortality in patients with hip replacement. Methods: According to the inclusion and exclusion criteria, patients who were undergoing hip replacement for the first time under general or intraspinal anesthesia, classified as ASA class I-IV, and aged ≥65 years were selected. We collected the general data, past medical history, preoperative laboratory test results, perioperative fluid intake and outflow data, perioperative anesthesia and related drug data, postoperative laboratory results, and correlation time index. Patients with preoperative combined nerve block were included in the N group, and those without combined nerve block were included in the NN group. The patients were followed up via telephone call to assess survival outcomes at 3 years after surgery. Propensity score matching and uni- and multivariate analyses were performed to determine the influence of nerve block and other related factors on postoperative mortality. Results: A total of 743 patients were included in this study, including 262 in the N group and 481 in the NN group. Two hundred five patients in both groups remained after propensity score matching. Main result: Preoperative nerve block was associated with reduced mortality three years after surgery. Conclusion: Nerve block reduces the incidence of 3-year postoperative mortality, and composite nerve block with general anesthesia and neuraxial anesthesia is worthy of promotion.

Effect of Prophylactic Placement of Percutaneous Endoscopic Gastrostomy on the Surgical Prognosis in Patients With Oral Cancer: A Pilot Study.

This study assessed the application of prophylactic percutaneous endoscopic gastrostomy (pPEG) in patients with newly diagnosed oral cancer (OC) who underwent surgery and were ready for subsequential chemoradiation. In total, 113 patients who underwent OC surgical treatment were divided into pPEG (n = 26), nasogastric tube (n = 54), and oral feeding (n = 33) groups. Their baseline characteristics, surgery-related outcomes, and nutritional data were analyzed using the Wilcoxon rank-sum test and χ2 test. No statistical significance was shown among the 3 groups using different flaps for reconstructing OC-related defects (P > 0.05). Patients of the pPEG group had the lowest incidence of surgical site infection (SSI; 23.1%, P = 0.006), but the longest hospital stay (24.1 ± 7.9 d, P < 0.001). Prophylactic percutaneous endoscopic gastrostomy may decrease the frequency of SSI but increase the length of hospitalization in SSI OC. However, multicentric prospective clinical controlled trials with large sample sizes are needed to further validate our findings.

Di (2-ethylhexyl) phthalate induced lipophagy-related renal ferroptosis in quail (Coturnix japonica).

Di(2-ethylhexyl) phthalate (DEHP) is a synthetic chemical applied as a plasticizer. As an environmental toxicant, DEHP poses a serious health threat. Many studies have revealed that DEHP can cause lead to various degrees of damage to the kidney. However, the evidence of DEHP-induced renal ferroptosis has not been reported. The purpose of this work was to probe the specific role of lipophagy in DEHP-induced renal injury and to investigate the relationship between lipophagy and ferroptosis. Quail were treated with DEHP (250 mg/kg BW/day, 500 mg/kg BW/day and 750 mg/kg BW/day) for 45 days. Microstructural and ultrastructural observations showed that DEHP caused damage to glomerular and tubular cells, and autophagy with multilayer structures were observed, suggesting that DEHP can induce lipophagy. The results indicated that the iron homeostasis was abnormal and the lipid peroxidation was increased. SLC7A11 and SLC3A2 were down-regulated. PTGS2, ACSL4 and LPCAT3 were elevated. In conclusion, DEHP could induce lipid peroxidation, lead to ferroptosis, and damage renal cells. Therefore, the relationship between lipophagy and ferroptosis was elucidated, which provided a new basis for intervention and prevention of DEHP increased diseases.

Nano-selenium alleviates cadmium-induced neurotoxicity in cerebrum via inhibiting gap junction protein connexin 43 phosphorylation.

Cadmium (Cd) as a ubiquitous toxic heavy metal is reported to affect the nervous system. Selenium (Se) has been shown to have antagonistic effects against heavy metal toxicity. In addition, it shows potential antioxidant and anti-inflammatory properties. Thus, the purpose of this study was to determine the possible mechanism of brain injury after high Cd exposure and the mitigation of Nano-selenium (Nano-Se) against Cd-induced brain injury. In this study, the Cd-treated group showed a decrease in the number of neurons in brain tissue, swelling of the endoplasmic reticulum and mitochondria, and the formation of autophagosomes. Nano-Se intervention restored Cd-caused alterations in neuronal morphology, endoplasmic reticulum, and mitochondrial structure, thereby reducing neuronal damage. Furthermore, we found that some differentially expressed genes were involved in cell junction and molecular functions. Subsequently, we selected eleven (11) related differentially expressed genes for verification. The qRT-PCR results revealed the same trend of results as determined by RNA-Seq. Our findings also showed that Nano-Se supplementation alleviated Cx43 phosphorylation induced by Cd exposure. Based on immunofluorescence colocalization it was demonstrated that higher expression of GFAP and lower expressions of Cx43 were restored by Nano-Se supplementation. In conclusion, the data presented in this study establish a direct association between the phosphorylation of Cx43 and the occurrence of autophagy and neuroinflammation. However, it is noteworthy that the introduction of Nano-Se supplementation has been observed to mitigate these alterations. These results elucidate the relieving effect of Nano-Se on Cd exposure-induced brain injury.

A PRISMA meta-analysis for diagnostic value of microRNA-21 in head and neck squamous cell carcinoma along with bioinformatics research.

OBJECTIVES: The use of miR-21 expression remains vague in diagnosis of head and neck squamous cell carcinoma (HNSCC). This study aimed to systematically evaluate the diagnostic potential of the miR-21 expression in patients with HNSCCs through investigating and summarizing the results reported in the literature. METHODS: Extant medical databases were examined for articles of clinical study assessing the miR-21 expression in HNSCC cases, published in the past 20 years. Bioinformatics research was also performed for finding miR-21 targets differentially expressed in HNSCC so as to present their biological behaviors. RESULTS: Our meta-analysis comprised 11 studies including 622/450 cases in HNSCC/control group. Forest plots displayed miR-21 which possessed significantly good specificity (0.76, p < 0.001) and sensitivity (0.80, p < 0.001). Diagnostic odds ratio was 2.46 (95% CI 1.87-3.24). Positive and negative likelihood ratio was 3.40 (95% CI 1.94-5.97) and 0.26 (95% CI 0.18-0.38), respectively. Area under the receiver operating characteristic curve was 0.85. CONCLUSION: This study is the highest level of evidence presently available in diagnosing HNSCC. This PRISMA meta-analysis indicated that the pooled results were robust, confirming the oncogenic potential of miR-21 that could be used successfully as a screening biomarker in HNSCC patients. Specifically, the overexpression of miR-21 in these patients presents a worse survival outcome.

Radioresistance or/and radiosensitivity of head and neck squamous cell carcinoma: biological angle.

OBJECTIVE: This narrative review aimed to compile and summarize clinically relevant literature in radiation therapy and to discuss the potential in radioresistant and radiosensitive head and neck squamous cell carcinoma (HNSCC). METHODS AND MATERIALS: Google Scholar, PubMed, and the Cochrane Library were retrieved using combined key words such as "radiotherapy" and "head and neck cancer." Search strings additionally queried were "radioresistant," "radiosensitive," "head and neck region," "squamous cell carcinoma," in combination with Boolean operators 'AND' and 'OR.' Subsequently, the resulting publications were included for review of the full text. RESULTS: Radiotherapeutic responses currently in clinical observation referred to HNSCC scoping were selected into this review. The compiled mechanisms were then detailed concerning on the clinical significance, biological characteristics, and molecular function. CONCLUSIONS: Brachytherapy or/and external-beam radiotherapy are crucial for treating HNSCC especially the early stage patients, but in some patients with locally advanced tumors, their outcome with radiation therapy is poor due to obvious radioresistance. The curative effects mainly depend on the response to radiation therapy so an updated review is needed to optimize further applications in HNSCC radiotherapy.

Effect of Prognostic Factors of Postoperative Radiotherapy in Oral Squamous Cell Carcinoma: A SEER-Based Study.

Objective: The treatment of oral squamous cell carcinoma (OSCC) is dominated by surgery and radiochemotherapy, but its prognosis is still unsatisfactory, with around five tenths of 5-year survival. This study aimed to assess the prognosis of OSCC patients treated with surgery with and without postoperative radiotherapy. Study Design: Retrospective study. Methods: The clinicopathological information and follow-up datasets on patients with OSCC (T1-4 and/or N+) registered from 2010 to 2015 were downloaded from the Surveillance, Epidemiology, and End Results database. Totally 7231 enrolled subjects were divided into a case group (surgery alone, n = 4167) and a control group (surgery combined with postoperative radiotherapy, n = 3064). One-to-one matching was performed by propensity score matching to make the baseline data comparable between the 2 subgroups. Multivariate Cox regression analysis was used to calculate hazard ratios (HR) of various clinicopathological features. The Kaplan-Meier method and log-rank test were used to plot the survival curves. Results: The majority of patients in case group were tumor stage I (n = 2569, 61.7%), whereas most patients in control group were stages III to IV (n = 2360, 77.1%). In the case group, the 1-, 3-, and 5-year overall survival (OS; 76%, 59.5%, 53.7%) were significantly lower than those of the control group (85.1%, 64.1%, 55.8%; P < .0001). Similarly, the 1-, 3-, and 5-year cancer-specific survival (CSS) of the case group (80.2%, 66.6%, 63.3%) were significantly lower than those of the control group (87.2%, 69.3%, 63.9%, respectively; P < .0001). Cox multivariate analysis indicated that age, differentiation, clinical stage, and tumor-node-metastasis stage affected the prognosis of OSCC patients, while postoperative radiotherapy was a protective factor (OS: HR = 0.649, P < .001; CSS: HR = 0.702, P < .001). Conclusions: Postoperative radiation was an independent protective factor, hence, the combination of surgery plus radiotherapy is more beneficial for the survival of patients with OSCC, particularly for advanced cases.

A network meta-analysis of risk factors of infection among close contacts of COVID-19.

Objective: We aimed to use network meta-analysis to compare the impact of infection risk factors of close contacts with COVID-19, identify the most influential factors and rank their subgroups. It can provide a theoretical basis for the rapid and accurate tracking and management of close contacts. Methods: We searched nine databases from December 1, 2019 to August 2, 2023, which only took Chinese and English studies into consideration. Odd ratios (ORs) were calculated from traditional meta-estimated secondary attack rates (SARs) for different risk factors, and risk ranking of these risk factors was calculated by the surface under the cumulative ranking curve (SUCRA). Results: 25 studies with 152647 participants identified. Among all risk factors, the SUCRA of type of contact was 69.6 % and ranked first. Among six types of contact, compared with transportation contact, medical contact, social contact and other, daily contact increased risk of infection by 12.11 (OR: 12.11, 95 % confidence interval (CI): 6.51-22.55), 7.76 (OR: 7.76, 95 % CI: 4.09-14.73), 4.65 (OR: 4.65, 95 % CI: 2.66-8.51) and 8.23 OR: 8.23, 95 % CI: 4.23-16.01) times, respectively. Overall, SUCRA ranks from highest to lowest as daily contact (94.7 %), contact with pollution subjects (78.4 %), social contact (60.8 %), medical contact (31.8 %), other (27.9 %), transportation contact (6.4 %). Conclusion: The type of contact had the greatest impact on COVID-19 close contacts infection among the risk factors we included. Daily contact carried the greatest risk of infection among six types of contact, followed by contact with pollution subjects, social contact, other, medical contact and transportation contact. The results can provide scientific basis for rapid assess the risk of infection among close contacts based on fewer risk factors and pay attention to high-risk close contacts during management, thereby reducing tracking and management costs.