RNA-seq analysis of mitochondria-related genes regulated by AMPK in the human trophoblast cell line BeWo.

BACKGROUND: How AMP activated protein kinase (AMPK) signaling regulates mitochondrial functions and mitophagy in human trophoblast cells remains unclear. This study was designed to investigate potential players mediating the regulation of AMPK on mitochondrial functions and mitophagy by next generation RNA-seq. METHODS: We compared ATP production in protein kinase AMP-activated catalytic subunit alpha 1/2 (PRKAA1/2) knockdown (AKD) and control BeWo cells using the Seahorse real-time ATP rate test, then analyzed gene expression profiling by RNA-seq. Differentially expressed genes (DEG) were examined by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Then protein-protein interactions (PPI) among mitochondria related genes were further analyzed using Metascape and Ingenuity Pathway Analysis (IPA) software. RESULTS: Both mitochondrial and glycolytic ATP production in AKD cells were lower than in the control BeWo cells (CT), with a greater reduction of mitochondrial ATP production. A total of 1092 DEGs were identified, with 405 upregulated and 687 downregulated. GO analysis identified 60 genes associated with the term 'mitochondrion' in the cellular component domain. PPI analysis identified three clusters of mitochondria related genes, including aldo-keto reductase family 1 member B10 and B15 (AKR1B10, AKR1B15), alanyl-tRNA synthetase 1 (AARS1), mitochondrial ribosomal protein S6 (MRPS6), mitochondrial calcium uniporter dominant negative subunit beta (MCUB) and dihydrolipoamide branched chain transacylase E2 (DBT). CONCLUSIONS: In summary, this study identified multiple mitochondria related genes regulated by AMPK in BeWo cells, and among them, three clusters of genes may potentially contribute to altered mitochondrial functions in response to reduced AMPK signaling.

Effect of Anions on Deformation of Gallium-Based Liquid Metal in Solution.

In this study, deformation behaviors of gallium-based liquid metals in acidified cupric sulfate or cupric chloride solutions with varying concentrations of chloride anion or sulfate anion were investigated to explore their potential applications in soft machines and electronics. Gallium-based liquid metals are known for their unique deformability, making them promising materials for various fields. Previous research has shown that deformation of the liquid metal can be achieved in the presence of acidified cupric or ferric salts. However, the specific influence of different anions on the deformation process remains unclear. Our findings indicate that the deformation rate of the liquid metal increases with higher concentrations of chloride ions and decreases with higher concentrations of sulfate ions in the solution. UV-vis absorbance spectra of the solutions were analyzed to identify the formation of hydrated cupric cations. It was observed that increasing the concentration of Cl- ions promotes the formation of cupric-chloro complexes, thereby reducing the concentration of hydrated cupric ions in the solution. Furthermore, the addition of sulfate ions to the solution enhances the ionic strength of the medium, leading to the dissociation of cupric-chloro complexes. Additionally, sulfate ions can form insoluble layers with gallium ions, which impede the deformation of the liquid metal. The deformation rate of the liquid metal was found to be inversely correlated with the concentration of cupric ions in the solution. These results provide valuable insights into the deformable behavior of gallium-based liquid metals and their potential applications in liquid metal-based soft robots. This study highlights the importance of understanding the role of different anions in the deformation process of liquid metals, shedding light on the design and optimization of soft machines and electronics utilizing these materials.

Effects of Comorbid Depressive Symptoms and Diabetes Mellitus on Functional Dyspepsia in Older Patients.

Objective: Diabetes mellitus (DM) is a global epidemic; comorbid depressive symptoms are highly prevalent worldwide and commonly manifests as physical symptoms, including functional dyspepsia (FD), a gastrointestinal psychosomatic disorder. This study aimed to explore the effects of comorbid depressive symptoms and DM on FD in older patients. Methods: In total, 420 older patients with DM completed measures of depression, anxiety, and FD. Relevant demographic characteristics and medical information were self-reported and obtained from the hospital information system. Results: Among older patients with DM, 30.48% had depressive symptoms. Patients with depressive symptoms were more likely to have FD than those without (42.19% vs. 20.21%, P = .000). Dyspepsia symptoms were more frequent in patients with depression (P = .022). The greater the amount of dyspepsia symptoms, the higher the depression symptoms score (P = .000). Furthermore, dyspepsia symptoms were positively correlated with depressive symptoms (r values were 0.292, 0.311, 0.297, 0.369; all had P < .05). Both FD subtypes, postprandial distress, and epigastric pain syndromes affected depressive symptoms (P < .05). Smoking was significantly associated with FD (P < .05). Diabetes mellitus complications, such as diabetic neuropathy, different therapeutic methods, and anxiety symptoms, influenced FD overlap (x 2 values were 6.298, 16.314, and 30.744; P < .05). Anxiety (odds ratio = 1.832, 95% Confidence Intervals (CI) 1.185-2.834) was a risk factor for FD in comorbid depressive symptoms and diabetes (P < .05). Conclusion: Comorbid depressive symptoms and DM overlapped with physical symptoms, such as FD, in older patients with DM. Lifestyle, diabetic factors, and anxiety were the associated risk factors.

Regulatory mechanism of TRIM21 in sepsis-induced acute lung injury by promoting IRF1 ubiquitination.

Sepsis-induced acute lung injury (ALI) is characterized by inflammatory damage to pulmonary endothelial and epithelial cells. The aim of this study is to probe the significance and mechanism of tripartite motif-containing protein 21 (TRIM21) in sepsis-induced ALI. The sepsis-induced ALI mouse model was established by cecum ligation and puncture. The mice were infected with lentivirus and treated with proteasome inhibitor MG132. The lung respiratory damage, levels of interleukin-6 (IL-6), tumour necrosis factor α (TNF-α), IL-10 and pathological changes were observed. The expression levels of TRIM21, interferon regulatory factors 1 (IRF1) and triggering receptor expressed on myeloid cells 2 (TREM2) were measured and their interactions were analysed. The ubiquitination level of IRF1 was detected. TRIM21 and TREM2 were downregulated and IRF1 was upregulated in sepsis-induced ALI mice. TRIM21 overexpression eased inflammation and lung injury. TRIM21 promoted IRF1 degradation via ubiquitination modification. IRF1 bonded to the TREM2 promoter to inhibit its transcription. Overexpression of IRF1 or silencing TREM2 reversed the improvement of TRIM21 overexpression on lung injury in mice. In conclusion, TRIM21 reduced IRF1 expression by ubiquitination to improve TREM2 expression and ameliorate sepsis-induced ALI.

Feasibility study of YSO/SiPM based detectors for virtual monochromatic image synthesis.

BACKGROUND: The development of photon-counting CT systems has focused on semiconductor detectors like cadmium zinc telluride (CZT) and cadmium telluride (CdTe). However, these detectors face high costs and charge-sharing issues, distorting the energy spectrum. Indirect detection using Yttrium Orthosilicate (YSO) scintillators with silicon photomultiplier (SiPM) offers a cost-effective alternative with high detection efficiency, low dark count rate, and high sensor gain. OBJECTIVE: This work aims to demonstrate the feasibility of the YSO/SiPM detector (DexScanner L103) based on the Multi-Voltage Threshold (MVT) sampling method as a photon-counting CT detector by evaluating the synthesis error of virtual monochromatic images. METHODS: In this study, we developed a proof-of-concept benchtop photon-counting CT system, and employed a direct method for empirical virtual monochromatic image synthesis (EVMIS) by polynomial fitting under the principle of least square deviation without X-ray spectral information. The accuracy of the empirical energy calibration techniques was evaluated by comparing the reconstructed and actual attenuation coefficients of calibration and test materials using mean relative error (MRE) and mean square error (MSE). RESULTS: In dual-material imaging experiments, the overall average synthesis error for three monoenergetic images of distinct materials is 2.53% ±2.43%. Similarly, in K-edge imaging experiments encompassing four materials, the overall average synthesis error for three monoenergetic images is 4.04% ±2.63%. In rat biological soft-tissue imaging experiments, we further predicted the densities of various rat tissues as follows: bone density is 1.41±0.07 g/cm3, adipose tissue density is 0.91±0.06 g/cm3, heart tissue density is 1.09±0.04 g/cm3, and lung tissue density is 0.32±0.07 g/cm3. Those results showed that the reconstructed virtual monochromatic images had good conformance for each material. CONCLUSION: This study indicates the SiPM-based photon-counting detector could be used for monochromatic image synthesis and is a promising method for developing spectral computed tomography systems.

RAB18 regulates extrahepatic siRNA-mediated gene silencing efficacy.

Small interfering RNAs (siRNAs) hold considerable therapeutic potential to selectively silence previously "undruggable" disease-associated targets, offering new opportunities to fight human diseases. This therapeutic strategy, however, is limited by the inability of naked siRNAs to passively diffuse across cellular membranes due to their large molecular size and negative charge. Delivery of siRNAs to liver through conjugation of siRNA to N-acetylgalactosamine (GalNAc) has been a success, providing robust and durable gene knockdown, specifically in hepatocytes. However, the poor delivery and silencing efficacy of siRNAs in other cell types has hindered their applications outside the liver. We previously reported that a genome-wide pooled knockout screen identified RAB18 as a major modulator of GalNAc-siRNA conjugates. Herein, we demonstrate RAB18 knockout/knockdown efficaciously enhances siRNA-mediated gene silencing in hepatic and extrahepatic cell lines and in vivo. Our results reveal a mechanism by which retrograde Golgi-endoplasmic reticulum (ER) transport and the intracellular lipid droplets (LDs) positively regulate siRNA-mediated gene silencing.

A new theoretical model for high-order harmonics of SH0 mode ultrasonic guided waves based on magnetostrictive mechanism.

In recent years, it was found that magnetostrictive ultrasonic guided wave transducers experimentally excited nonlinear harmonic components under a certain combination of dynamic and static magnetic fields. However, a satisfactory model for the relevant excitation mechanisms is not available. In this study, a new magnetostrictive guided wave excitation model was established and the causes for harmonics generation were analyzed. In addition, the calculation results of the model were obtained under different magnetic field parameters. We firstly changed the calculation conditions of magnetostrictive strain in the model and then theoretically calculated the odd and even harmonics of SH0 mode ultrasonic guided waves for the first time. Furthermore, the accuracy of the model was experimentally verified. By changing the strength ratio of the dynamic magnetic field to the static magnetic field (HD/HS), the excitation amplitudes of odd and even harmonics could be regulated with a magnetostrictive sensor. As the ratio of HD/HS increased, the normalized amplitude of the second harmonic firstly increased and then decreased, whereas the normalized amplitude of the third harmonic showed an exponential growth with different curvatures. This study enriched the theory of magnetostrictive guided wave excitation and provided a theoretical basis for the applications of magnetostrictive sensors.

High-resolution anionic velocity map imaging apparatus for dissociative electron attachment dynamics study.

Dissociative electron attachment (DEA) of a molecular target XY, e- + XY → XY- → X + Y-, is an important process in plasma, atmosphere, interstellar space, and ionizing radiation. DEA dynamics, i.e., the formation and fragmentation of an electron-molecule resonant complex, can be unveiled by measuring the product Y- with the velocity map imaging (VMI) technique. However, it is still challenging to achieve a high-resolution VMI measurement. Recently, we developed a high-resolution DEA apparatus that combined the VMI technique with a trochoidal electron monochromator. The energy spread (around 500 meV) of thermally emitted incident electrons can be reduced remarkably, but the monochromatized electrons become diffuse again in energy when being pulsed with an electric pulse applied on the grid electrode because the electron beam must be pulsed in the VMI measurement. Now this long-standing technical contradiction is settled by introducing a parallel resistance-capacitor circuit to the electrode of an electron gun. A delay-line detector is used for the VMI measurement, which allows the three-dimensional velocity or momentum images of multiple anionic yields to be recorded efficiently. Our high-resolution VMI apparatus works at a pulse frequency of 5 kHz and an energy spread of about 120-150 meV, and its credible performances are exhibited by the measurements of the DEA processes of CO(a3Π) and NO2.

The relationship between the Barthel Index and stroke-associated pneumonia in elderly patients and factors of SAP.

BACKGROUND: Stroke-associated pneumonia (SAP) is a common complication in stroke patients, and the Barthel Index (BI) is a well-established metric for assessing activities of daily living (ADL). However, the association between BI and SAP in acute ischemic stroke (AIS) patients remains unclear. This study aims to investigate the relationship between BI at admission and SAP, and explore the factors in AIS elderly patients. METHOD: Retrospective data were collected from ischemic stroke patients hospitalized at the Second Affiliated Hospital of Nanchang University between January 2018 and July 2021, including their basic demographic and laboratory test results. Restricted cubic spline regression, multivariate logistic regression analysis, and receiver operating characteristic (ROC) curve analysis were employed to investigate the relationship between BI and SAP. Additionally, the Shapley Additive exPlanations (SHAP) method was used to identify the factors influencing SAP. RESULTS: The study included 7,548 eligible stroke patients with a mean age of 75.1 ± 7.6 years, among which 41.14% were female. The SAP group demonstrated significantly lower BI compared to the non-SAP group (50.86 ± 35.60 vs. 75.27 ± 26.33, P < 0.001). Additionally, a conspicuous trend of decreasing SAP risk across the Q1-4 groups was observed (P < 0.001). The RCS analysis further confirmed a gradual reduction in SAP risk with increasing BI. Based on the clinical model, both the BI (NRI = 0.014, P = 0.005; IDI = 0.04, P < 0.001) and the NIHSS score (NRI = 0.09, P = 0.03; IDI = 0.025, P < 0.001) demonstrated additional predictive value for SAP. Multivariate logistic regression and SHAP analysis identified WBC, CONUT, TG, UA, and RBC levels, as well as the type of health insurance (urban employee basic medical insurance), as important independent predictors of SAP. CONCLUSION: BI at admission constitutes a risk factor for the onset of SAP in elderly patients with AIS, Compared to the NIHSS and mRS score, BI may be a more reliable and practical predictor of SAP.

Case report: A rare case of neurocytoma of the Vth cranial nerve.

We report a case of neurocytoma originating from cranial nerve V. A 53-year-old female patient presented with a 20-day history of right frontotemporal facial paresthesia and pain. Magnetic resonance imaging (MRI) showed a 2.5-cm × 1.4-cm "dumbbell" enhancing lesion located in the cisternal segment of cranial nerve V with extension into Meckel's cave, and the signal characteristics were suggestive of trigeminal neurinoma. The lesion was resected through a subtemporal middle cranial fossa approach. Intraoperative findings revealed that the tumor originated from the cisternal segment of cranial nerve V and extended into Meckel's cave through the trigeminal foramen. No dural attachment was found. The tumor was debulked using sharp dissection and bipolar cautery under the microscope. Extraventricular neurocytomas (EVNs) are extremely rare tumors of the central nervous system. To date, only two cases of neurocytomas arising from cranial nerve VIII have been described. This paper summarizes the clinicopathological features of a case of neurocytoma originating from the cisternal segment of cranial nerve V with extension into Meckel's cave and expounds the relevant diagnoses and treatments, which may provide a practical clinical basis and experience for the diagnosis and treatment of EVN in the future.

Experimental demonstration of frequency- downconverted arm-length stabilization for a future upgraded gravitational wave detector.

Ground-based laser interferometric gravitational wave detectors (GWDs) consist of multiple optical cavity systems whose lengths need to be interferometrically controlled. An arm-length stabilization (ALS) system has played an important role in bringing these interferometers into an operational state and enhancing their duty cycle. The sensitivity of these detectors can be improved if the thermal noise of their test mass mirror coatings is reduced. Crystalline AlGaAs coatings are a promising candidate for this. However, the current ALS system with a frequency-doubled 532 nm light is no longer an option with AlGaAs coatings because the 532 nm light is absorbed by AlGaAs coatings due to the narrow bandgap of GaAs. Therefore, alternative locking schemes must be developed. In this Letter, we describe an experimental demonstration of a novel ALS scheme, to the best of our knowledge, which is compatible with AlGaAs coatings. This ALS scheme will enable the use of AlGaAs coatings in current and future terrestrial gravitational wave detectors.

Assessment of toxicity changes induced by exposure of human cells to lunar dust simulant.

The toxicity of lunar dust (LD) to astronauts' health has been confirmed in the Apollo missions and subsequent biological experiments. Therefore, it is crucial to understand the biological toxicity of lunar dust for future human missions to the Moon. In this study, we exposed human lung epithelial cells (BEAS-2B) and peripheral blood B lymphocytes (AHH-1) to varying concentrations (0, 500, 1000, and 1500 µg/ml) of a lunar dust simulant (LDS) called CLDS-i for 24 and 48 h. The results provided the following key findings: (1) LDS induction of cell damage occurred through oxidative stress, with the levels of reactive oxygen species (ROS) in BEAS-2B cells being dependent on the duration of exposure. (2) Necrosis and early apoptosis were observed in BEAS-2B cells and AHH-1 cells, respectively. In addition, both cells showed lysosomal damage. (3) Genes CXCL1, SPP1, CSF2, MMP1, and POSTN are implicated in immune response and cytoskeletal arrangement regulation in BEAS-2B cells. Considering the similarities in composition and properties between CLDS-i and real lunar dust, our findings not only enhance the understanding of LDS toxicity, but also contribute to a better comprehension of the genomic alterations and molecular mechanisms underlying cellular toxicity induced by LD. These insights will contribute to the development of a biotoxicology framework aimed at safeguarding the health of astronauts and, consequently, facilitating future human missions to the Moon.

Dry age-related macular degeneration classification from optical coherence tomography images based on ensemble deep learning architecture.

Background: Dry age-related macular degeneration (AMD) is a retinal disease, which has been the third leading cause of vision loss. But current AMD classification technologies did not focus on the classification of early stage. This study aimed to develop a deep learning architecture to improve the classification accuracy of dry AMD, through the analysis of optical coherence tomography (OCT) images. Methods: We put forward an ensemble deep learning architecture which integrated four different convolution neural networks including ResNet50, EfficientNetB4, MobileNetV3 and Xception. All networks were pre-trained and fine-tuned. Then diverse convolution neural networks were combined. To classify OCT images, the proposed architecture was trained on the dataset from Shenyang Aier Excellence Hospital. The number of original images was 4,096 from 1,310 patients. After rotation and flipping operations, the dataset consisting of 16,384 retinal OCT images could be established. Results: Evaluation and comparison obtained from three-fold cross-validation were used to show the advantage of the proposed architecture. Four metrics were applied to compare the performance of each base model. Moreover, different combination strategies were also compared to validate the merit of the proposed architecture. The results demonstrated that the proposed architecture could categorize various stages of AMD. Moreover, the proposed network could improve the classification performance of nascent geographic atrophy (nGA). Conclusion: In this article, an ensemble deep learning was proposed to classify dry AMD progression stages. The performance of the proposed architecture produced promising classification results which showed its advantage to provide global diagnosis for early AMD screening. The classification performance demonstrated its potential for individualized treatment plans for patients with AMD.

Pan-immune-inflammation value as a prognostic biomarker for colon cancer and its variation by primary tumor location.

BACKGROUND: A growing body of research indicates significant differences between left-sided colon cancers (LCC) and right-sided colon cancers (RCC). Pan-immune-inflammation value (PIV) is a systemic immune response marker that can predict the prognosis of patients with colon cancer. However, the specific distinction between PIV of LCC and RCC remains unclear. AIM: To investigate the prognostic and clinical significance of PIV in LCC and RCC patients. METHODS: This multicenter retrospective cohort study included 1510 patients with colon cancer, comprising 801 with LCC and 709 with RCC. We used generalized lifting regression analysis to evaluate the relative impact of PIV on disease-free survival (DFS) in these patients. Kaplan-Meier analysis, as well as univariate and multivariate analyses, were used to examine the risk factors for DFS. The correlation between PIV and the clinical characteristics was statistically analyzed in these patients. RESULTS: A total of 1510 patients {872 female patients (58%); median age 63 years [interquartile ranges (IQR): 54-71]; patients with LCC 801 (53%); median follow-up 44.17 months (IQR 29.67-62.32)} were identified. PIV was significantly higher in patients with RCC [median (IQR): 214.34 (121.78-386.72) vs 175.87 (111.92-286.84), P < 0.001]. After propensity score matching, no difference in PIV was observed between patients with LCC and RCC [median (IQR): 182.42 (111.88-297.65) vs 189.45 (109.44-316.02); P = 0.987]. PIV thresholds for DFS were 227.84 in LCC and 145.99 in RCC. High PIV (> 227.84) was associated with worse DFS in LCC [PIV-high: Adjusted hazard ratio (aHR) = 2.39; 95% confidence interval: 1.70-3.38; P < 0.001] but not in RCC (PIV-high: aHR = 0.72; 95% confidence interval: 0.48-1.08; P = 0.114). CONCLUSION: These findings suggest that PIV may predict recurrence in patients with LCC but not RCC, underscoring the importance of tumor location when using PIV as a colon cancer biomarker.

Malnutrition is associated with severe outcome in elderly patients hospitalised with COVID-19.

Some studies have identified influencing factors of COVID-19 illness in elderly, such as underlying diseases, but research on the effect of nutritional status is still lacking. This study retrospectively examined the influence of nutritional status on the outcome of elderly COVID-19 inpatients. A retrospective analysis of the clinical data of 4241 COVID-19 patients who were admitted to a third-class hospital of Nanchang between November 1, 2022 and January 31, 2023 was conducted. Nutritional status was assessed using the prognostic nutritional index (PNI) and controlling nutritional status score (CONUT). The influence of nutritional status on the outcome of COVID-19 patients was determined through multivariate adjustment analysis, restrictive cubic spline, and receiver operating characteristic curve (ROC). Compared with mild/no malnutrition, severe malnutrition substantially increased the critical outcome of COVID-19. A linear relationship was observed between the odds ratio (OR) and PNI and CONUT (P > 0.05). The area under the ROC curve indicated that PNI was the better predictor. The optimal cutoff value of PNI was 38.04 (95%CI: 0.797 ~ 0.836, AUC = 0.817), with a sensitivity of 70.7% and a specificity of 79.6%. The critical illness of elderly COVID-19 patients shows a linear relationship with malnutrition at admission. The use of PNI to assess the prognosis of COVID-19 eldeely patients is reliable, highlighting the importance for doctors to closely pay attention to the nutritional status of COVID-19 patients. Focusing on nutritional status in clinical practice can effectively reduce the critical illness of elderly COVID-19 patients.

Chevalierlin: A spirocyclic alkaloid from a hydrothermal vent associated fungus Aspergillus chevalieri TW132-65.

A previously undescribed spirodiketopiperazine-indole alkaloid, chevalierlin (1), two pairs of previously undescribed dihydroisocoumarin enantiomers eurotiumides H-I (2-3), as well as six related known compounds (4-9) were isolated from the culture of a hydrothermal vent associated fungus Aspergillus chevalieri TW132-65. Their structures were unambiguously determined by NMR, mass spectrometry, and ECD calculations. Chevalierlin (1) exhibits moderate cytotoxic activities with IC50 values of 6.20 ± 0.05 µM and 7.68 ± 0.01 µM against Namalwa and Raji cell lines.

Dicitrinols A-C: Citrinin Derivatives from Hydrothermal Vent-Associated Fungus Penicillium citrinum TW132-59.

Three new unusual citrinin derivatives with a unique 6/5/7/5 core, dicitrinols A-C (1-3, respectively), were isolated via the fermentation of hydrothermal vent-associated fungus Penicillium citrinum TW132-59. Their structures were unambiguously determined by nuclear magnetic resonance, mass spectrometry, and electronic circular dichroism calculations. Dicitrinols A-C represent a novel cage carbon skeleton with a decahydro-5,9,4-(epipropane[1,1,3]triyl)cycloocta[b]furan ring system. Dicitrinols A-C showed moderate antifungal activity against Candida albicans, Cryptococcus neoformans, and Fusarium oxysporum and antibacterial activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii with minimum inhibitory concentrations ranging from 4 to 16 µg/mL.

A Novel Accurate Peak Extraction Algorithm of Mass Spectrometry Based on Iterative Adaptive Curve Fitting.

In the analysis of mass spectrometry, the peak identification from the overlapped region is necessary yet difficult. Although various methods have been developed to identify these peaks, especially the continuous wavelet transformation, their applications are still limited and it is hard to deal with the complex overlapped peaks. In this study, a novel peak extraction algorithm of mass spectrometry based on iterative adaptive curve fitting is proposed to address these challenges. It fully utilizes the global optimization characteristics of adaptive curve fitting. Initial peak parameters are obtained using a window searching method, and the residuals between the adaptive fitting peak and the original data indicate the fit's effectiveness and provide information about the peaks in overlap. Using this information, we performed iterative adaptive fitting, continuously updating the overlapped peaks until the residuals met the completion criteria. All of the peaks within the overlapped region can be successfully extracted by the final fitting. The proposed method is evaluated by the simulated data, the real signal from a public data set, and the spectra of two different mass spectrometry instruments. The results demonstrate that this method can more effectively extract peaks with severe overlap and multiple overlapped peaks, resist noise interference, and offer the potential to process peaks with a high dynamic range. More importantly, the proposed method accurately identifies overlapped peaks in the actual spectra from various mass spectrometry instruments, which helps the qualitative and quantitative analyses to a great extent.

Nme8 is essential for protection against chemotherapy drug cisplatin-induced male reproductive toxicity in mice.

Cisplatin (CP), a chemotherapy drug commonly used in cancers treatment, causes serious reproductive toxicity. With younger cancer patients and increasing survival rates, it is important to preserve their reproductive capacity. NME8 is highly expressed in testis and contains thioredoxin and NDPK domains, suggesting it may be a target against the CP-induced reproductive toxicity. We deleted exons 6-7 of the Nme8 in mice based on human mutation sites and observed impaired transcript splicing. In mice, Nme8 was not essential for spermatogenesis, possibly due to functional compensation by its paralog, Nme5. Nme8 expression was elevated and translocated to the nucleus in response to two weeks of CP treatment. Under CP treatment, Nme8 deficiency further impaired antioxidant capacity, induced lipid peroxidation and increased ROS level, and failed to activate autophagy, resulting in aggravated DNA damage in testes and sperm. Consequently, the proliferation and differentiation of spermatogonia and the meiosis of spermatocyte were almost completely halted, and sperm motility was impaired. Our research indicates that NME8 protects against CP-induced testis and sperm damage. This may provide new insights into the physiological functions of the Nme family and potential targets for preserving fertility in young male cancer patients.

Integrative analyses of bulk and single-cell RNA-seq reveals the correlation between SPP1+ macrophages and resistance to neoadjuvant chemoimmunotherapy in esophageal squamous cell carcinoma.

Neoadjuvant chemoimmunotherapy (NACI) has significant implications for the treatment of esophageal cancer. However, its clinical efficacy varies considerably among patients, necessitating further investigation into the underlying mechanisms. The rapid advancement of single-cell RNA sequencing (scRNA-seq) technology facilitates the analysis of patient heterogeneity at the cellular level, particularly regarding treatment outcomes. In this study, we first analyzed scRNA-seq data of esophageal squamous cell carcinoma (ESCC) following NACI, obtained from the Gene Expression Omnibus (GEO) database. After performing dimensionality reduction, clustering, and annotation on the scRNA-seq data, we employed CellChat to investigate differences in cell-cell communication among samples from distinct efficacy groups. The results indicated that macrophages in the non-responder exhibited stronger cell communication intensity compared to those in responders, with SPP1 and GALECTIN signals showing the most significant differences between the two groups. This finding underscores the crucial role of macrophages in the efficacy of NACI. Subsequently, reclustering of macrophages revealed that Mac-SPP1 may be primarily responsible for treatment resistance, while Mac-C1QC appears to promote T cell activation. Finally, we conducted transcriptome sequencing on ESCC tissues obtained from 32 patients who underwent surgery following NACI. Utilizing CIBERSORT, CIBERSORTx, and WGCNA, we analyzed the heterogeneity of tumor microenvironment among different efficacy groups and validated the correlation between SPP1+ macrophages and resistance to NACI in ESCC using publicly available transcriptome sequencing datasets. These findings suggest that SPP1+ macrophages may represent a key factor contributing to resistance against NACI in ESCC.