Effect of Ultraviolet Radiation on Properties of Ge2Sb2Te5 Phase Change Films.

With the expanding utilization of space technology, the stability of electronic components' performance in radiation environments has garnered significant attention. In this study, we prepared Ge2Sb2Te5 phase change films and memory units on silicon substrates to explore the influence of ultraviolet (UV) radiation on their characteristics. The experimental findings revealed that UV irradiation at a power density of 450 mW/cm2 decreased the amorphous resistance and thermal stability of Ge2Sb2Te5 films, impeding their multistage storage performance. Nevertheless, the amorphous state could still undergo effective transformation into a crystalline state. Furthermore, UV irradiation triggered the photoelectric effect, narrowing the band gap and causing a redshift of the Raman peak in amorphous films. Remarkably, the surface properties of Ge2Sb2Te5 films remained unchanged under irradiation. The phase change memory device based on Ge2Sb2Te5 film retained its SET-RESET conversion capability at a pulse width of 100 ns post-UV irradiation, demonstrating resilience against UV radiation. This study offers the practical insights for the application of phase change memory in space radiation environments.

KMT2A and chronic inflammation as potential drivers of sporadic parathyroid adenoma.

BACKGROUND: Sporadic parathyroid adenoma (PA) is the most common cause of hyperparathyroidism, yet the mechanisms involved in its pathogenesis remain incompletely understood. METHODS: Surgically removed PA samples, along with normal parathyroid gland (PG) tissues that were incidentally dissected during total thyroidectomy, were analysed using single-cell RNA-sequencing with the 10× Genomics Chromium Droplet platform and Cell Ranger software. Gene set variation analysis was conducted to characterise hallmark pathway gene signatures, and single-cell regulatory network inference and clustering were utilised to analyse transcription factor regulons. Immunohistochemistry and immunofluorescence were performed to validate cellular components of PA tissues. siRNA knockdown and gene overexpression, alongside quantitative polymerase chain reaction, Western blotting and cell proliferation assays, were conducted for functional investigations. RESULTS: There was a pervasive increase in gene transcription in PA cells (PACs) compared with PG cells. This is associated with high expression of histone-lysine N-methyltransferase 2A (KMT2A). High KMT2A levels potentially contribute to promoting PAC proliferation through upregulation of the proto-oncogene CCND2, which is mediated by the transcription factors signal transducer and activator of transcription 3 (STAT3) and GATA binding protein 3 (GATA3). PA tissues are heavily infiltrated with myeloid cells, while fibroblasts, endothelial cells and macrophages in PA tissues are commonly enriched with proinflammatory gene signatures relative to their counterparts in PG tissues. CONCLUSIONS: We revealed the previously underappreciated involvement of the KMT2A‒STAT3/GATA3‒CCND2 axis and chronic inflammation in the pathogenesis of PA. These findings underscore the therapeutic promise of KMT2A inhibition and anti-inflammatory strategies, highlighting the need for future investigations to translate these molecular insights into practical applications. HIGHLIGHTS: Single-cell RNA-sequencing reveals a transcriptome catalogue comparing sporadic parathyroid adenomas (PAs) with normal parathyroid glands. PA cells show a pervasive increase in gene expression linked to KMT2A upregulation. KMT2A-mediated STAT3 and GATA3 upregulation is key to promoting PA cell proliferation via cyclin D2. PAs exhibit a proinflammatory microenvironment, suggesting a potential role of chronic inflammation in PA pathogenesis.

Development of a novel disulfidptosis-related lncRNA signature for prognostic and immune response prediction in clear cell renal cell carcinoma.

Disulfidptosis, a novel form of regulated cell death, occurs due to the aberrant accumulation of intracellular cystine and other disulfides. Moreover, targeting disulfidptosis could identify promising approaches for cancer treatment. Long non-coding RNAs (lncRNAs) are known to be critically implicated in clear cell renal cell carcinoma (ccRCC) development. Currently, the involvement of disulfidptosis-related lncRNAs in ccRCC is yet to be elucidated. This study primarily dealt with identifying and validating a disulfidptosis-related lncRNAs-based signature for predicting the prognosis and immune landscape of individuals with ccRCC. Clinical and RNA sequencing data of ccRCC samples were accessed from The Cancer Genome Atlas (TCGA) database. Pearson correlation analysis was conducted for the identification of the disulfidptosis-related lncRNAs. Additionally, univariate Cox regression analysis, Least Absolute Shrinkage and Selection Operator Cox regression, and stepwise multivariate Cox analysis were executed to develop a novel risk prognostic model. The prognosis-predictive capacity of the model was then assessed using an integrated method. Variation in biological function was noted using GO, KEGG, and GSEA. Additionally, immune cell infiltration, the tumor mutational burden (TMB), and tumor immune dysfunction and exclusion (TIDE) scores were calculated to investigate differences in the immune landscape. Finally, the expression of hub disulfidptosis-related lncRNAs was validated using qPCR. We established a novel signature comprised of eight lncRNAs that were associated with disulfidptosis (SPINT1-AS1, AL121944.1, AC131009.3, AC104088.3, AL035071.1, LINC00886, AL035587.2, and AC007743.1). Kaplan-Meier and receiver operating characteristic curves demonstrated the acceptable predictive potency of the model. The nomogram and C-index confirmed the strong correlation between the risk signature and clinical decision-making. Furthermore, immune cell infiltration analysis and ssGSEA revealed significantly different immune statuses among risk groups. TMB analysis revealed the link between the high-risk group and high TMB. It is worth noting that the cumulative effect of the patients belonging to the high-risk group and having elevated TMB led to decreased patient survival times. The high-risk group depicted greater TIDE scores in contrast with the low-risk group, indicating greater potential for immune escape. Finally, qPCR validated the hub disulfidptosis-related lncRNAs in cell lines. The established novel signature holds potential regarding the prognosis prediction of individuals with ccRCC as well as predicting their responses to immunotherapy.

The prognostic value of red blood cell distribution width for pulmonary infection in elderly patients received abdominal surgery with tracheal intubation and general anesthesia.

BACKGROUND: Red blood cell distribution width (RDW) has been shown to be an important predictor of the occurrence of various inflammatory and infectious diseases. However, the predictive value of RDW for pulmonary infection in elderly patients undergoing abdominal surgery under general anesthesia with endotracheal intubation remains unclear. METHODS: A total of 200 eligible elderly patients who underwent abdominal surgery with endotracheal intubation and general anesthesia in our hospital from January 2019 to January 2022 were included in this study. During hospitalization, there were 64 cases with different degrees of pulmonary infection, and 136 cases without pulmonary infection. Participants' RDW levels were analyzed on admission. Serum levels of inflammatory factors in infected patients were analyzed during hospitalization. Multivariate logistic analysis was performed to evaluate clinical factors for pulmonary infection during hospitalization following-up abdominal surgery with endotracheal intubation and general anesthesia in elderly patients. Youden's J statistic was used to define the correlation. RESULTS: RDW at admission was independently associated with the risk of pulmonary infection in elderly patients undergoing general anesthesia with endotracheal intubation for abdominal surgery ([OR 1.952, 95% confidence interval 1.604 to 2.279, p=0.006]). RDW at admission was statistically positively correlated with inflammatory factors, including procalcitonin (p<0.001), C-reactive protein (p<0.001), and tumor necrosis factor-α (p<0.001), in elderly patients with postoperative pneumonia who underwent abdominal surgery. CONCLUSION: RDW at admission had predictive value for pulmonary infection in elderly patients undergoing abdominal surgery under general anesthesia with endotracheal intubation.

Serum Proteomic Signatures in Umbilical Cord Blood of Preterm Neonates Delivered by Women with Gestational Diabetes.

Background: Women who develop diabetes during pregnancy are at higher risk of preterm birth. Here, we identified differentially expressed proteins (DEPs) in the serum of umbilical cord blood samples obtained from preterm neonates delivered by women with gestational diabetes to provide therapeutic targets for clinical drug development. Materials and Methods: Umbilical cord blood was collected after delivery of preterm neonates by women with gestational diabetes and after delivery of healthy neonates by women without diabetes. DEPs in the serum samples were identified using liquid chromatography-tandem mass spectrometry. Gene Ontology (GO), cluster analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to determine the biological functions associated with these DEPs. Enzyme linked immunosorbent assay was used to confirm the key DEPs. Results: We found that 21 proteins were significantly upregulated, and 51 proteins were significantly downregulated in 72 DEPs in serum samples. GO analyses showed that the DEPs were mainly associated with the GO terms cellular process, biological regulation, cellular anatomical entity, and binding. KEGG signaling pathway analysis indicated that most of the upregulated DEPs were associated with the complement and coagulation cascades, Staphylococcus aureus infection, pertussis, HIF-1 signaling pathway and PPAR signaling pathway and that most of the downregulated DEPs were associated with the complement and coagulation cascades, dilated cardiomyopathy, pathways in cancer, Chagas disease, and hypertrophic cardiomyopathy. The results of KEGG pathway annotation and enrichment analyses indicated that changes in the complement and coagulation cascades may be importantly associated with preterm delivery of neonates by women with gestational diabetes. The key DEPs were confirmed by enzyme linked immunosorbent assay. Conclusion: Our proteomics and bioinformatics analyses identified several key proteins and the complement and coagulation cascades pathway that warrant further investigation as potential novel therapeutic targets in preterm delivery among women with gestational diabetes.

Upcycling of poly(ethylene terephthalate) to produce high-value bio-products.

More than 70 million tons of poly(ethylene terephthalate) (PET) are manufactured worldwide every year. The accumulation of PET waste has become a global pollution concern, motivating the urgent development of technologies to valorize post-consumer PET. The development of chemocatalytic and enzymatic approaches for depolymerizing PET to its corresponding monomers opens up new opportunities for PET upcycling through biological transformation. Here, we identify Rhodococcus jostii strain PET (RPET) that can directly use PET hydrolysate as a sole carbon source. We also investigate the potential of RPET to upcycle PET into value-added chemicals, using lycopene as a proof-of-concept product. Through rational metabolic engineering, we improve lycopene production by more than 500-fold over that of the wild type. In addition, we demonstrate the production of approximately 1,300 µg/L lycopene from PET by cascading this strain with PET alkaline hydrolysis. This work highlights the great potential of biological conversion as a means of achieving PET upcycling.

Regulation Networks of Non-Coding RNA-Associated ceRNAs in Cisplatin-Induced Acute Kidney Injury.

Cisplatin is widely used as a chemotherapeutic drug to treat various solid tumors. However, it often induces severe side effects, including nephrotoxicity, which limits its application in clinical settings. Furthermore, the underlying mechanisms of action are unclear. Here, we applied whole-transcriptome RNA sequencing to a cisplatin-induced acute kidney injury (CP-AKI) mouse model to evaluate competing endogenous RNA (ceRNA) networks. We found 4460 mRNAs, 1851 long non-coding RNAs, 101 circular RNAs, and 102 microRNAs significantly differentially expressed between CP-AKI and control mice. We performed gene set enrichment analysis to reveal the biological functions of the mRNAs and constructed non-coding RNA-associated ceRNA networks in CP-AKI mice. Two ceRNA regulatory pathways, Lhx1os-203/mmu-miR-21a-3p/Slc7a13 and circular RNA_3907/mmu-miR-185-3p/Ptprn, were validated using quantitative real-time PCR. The protein-protein interaction network indicated that Il6, Cxcl1, Cxcl2, and Plk1 serve as hub genes and are highly connected with the inflammatory response or DNA damage. Transcription factors, such as Stat3, Cebpb, and Foxm1, regulate gene expression levels in CP-AKI. Our study provides insight into non-coding RNA-associated ceRNA networks and mRNAs in CP-AKI and identifies potential treatment targets.

Comparison of Different Drying Methods for Asparagus [Asparagus cochinchinensis (Lour.) Merr.] Root Volatile Compounds as Revealed Using Gas Chromatography Ion Mobility Spectrometry.

Asparagus [Asparagus cochinchinensis (Lour.) Merr.] is a traditional herbal medicine plant commonly used to nourish yin, moisten dryness, and clear fire cough symptoms. Drying is an excellent option to conserve food materials, i.e., grains, fruits, vegetables, and herbs, reducing the raw materials volume and weight. This study aims to evaluate different drying approaches that could increase the value of asparagus, particularly as an ingredient in fast foods or as nutraceutical byproducts. The volatile components of asparagus roots were analyzed by using headspace-gas chromatography-ion mobility spectroscopy under different drying conditions, i.e., natural drying (ND) at ambient air temperature in the dark, well-ventilated room, temperature range 28-32°C, blast or oven drying at 50°C, heat pump or hot-air drying at temperature 50°C and air velocity at 1.5 ms-1 and vacuum freeze-drying at the temperature of -45°C and vacuum pressure of 10-30 Pa for 24 h. The findings revealed that the various drying processes had multiple effects on the color, odor index, and volatile compounds of the asparagus roots. As a result of the investigations, multiple characteristics of components, therefore, exploitation and comparison of various flavors; a total of 22 compounds were identified, such as alcohols, ketones, aldehydes, acids, esters, heterocyclic, and terpene. The present findings may help understand the flavor of the processed asparagus roots and find a better option for drying and processing.

Design and Production of Bispecific Antibodies.

With the current biotherapeutic market dominated by antibody molecules, bispecific antibodies represent a key component of the next-generation of antibody therapy. Bispecific antibodies can target two different antigens at the same time, such as simultaneously binding tumor cell receptors and recruiting cytotoxic immune cells. Structural diversity has been fast-growing in the bispecific antibody field, creating a plethora of novel bispecific antibody scaffolds, which provide great functional variety. Two common formats of bispecific antibodies on the market are the single-chain variable fragment (scFv)-based (no Fc fragment) antibody and the full-length IgG-like asymmetric antibody. Unlike the conventional monoclonal antibodies, great production challenges with respect to the quantity, quality, and stability of bispecific antibodies have hampered their wider clinical application and acceptance. In this review, we focus on these two major bispecific types and describe recent advances in the design, production, and quality of these molecules, which will enable this important class of biologics to reach their therapeutic potential.

Aberrant expression and mechanism of miR-130b-3p/phosphatase and tensin homolog in nephroblastoma in children.

Nephroblastoma is the most common renal tumor in children. Abnormal expression of microRNAs (miRs) has been reported to be involved in the progression of various types of cancers. However, the role and underlying mechanism of miR-130b-3p in nephroblastoma remains unknown. Therefore, the present study aimed to explore the role and possible mechanism of miR-130b-3p in nephroblastoma in children. The present study identified that miR-130b-3p was highly expressed in nephroblastoma tissues obtained from children with nephroblastoma. To better understand the functions and the molecular mechanisms of miR-130b-3p in nephroblastoma, TargetScan was used to identify the potential targets of miR-130b-3p. Phosphatase and tensin homolog (PTEN), was identified as a target gene of miR-130b-3p, and it was observed to be downregulated in nephroblastoma. Further analysis indicated that miR-130b-3p inhibitor could significantly reduce cell proliferation, induce apoptosis and suppress the Akt/nuclear factor-κB/survivin signaling pathway in nephroblastoma cells. Notably, all these effects of miR-130b-3p on nephroblastoma cells were reversed by PTEN-small interfering RNA. In summary, the present study suggested that the miR-130b-3p/PTEN axis could serve a critical role in the progression and development of nephroblastoma. It also suggests that miR-130b-3p might be a valuable clinical biomarker and therapeutic target for nephroblastoma in children.

Effects of epidural preemptive analgesia on stress reaction in retroperitoneal laparoscopic adrenalectomy surgery: a randomized controlled study.

OBJECTIVE: To compare the effects of general anesthesia combined with epidural preemptive analgesia with general anesthesia on stress reaction in the retroperitoneal laparoscopic surgery. METHODS: Forty patients with adrenal tumors undergoing retroperitoneal laparoscopic surgeries were randomly assigned into general anesthesia combined with epidural preemptive analgesia group (GE) and general anesthesia group (G). Each group had 20 cases. In the GE group, before the induction of general anesthesia, T10-T11 epidural puncture was performed and 0.2% bupivacaine 5-10 ml was injected to maintain the anesthesia level at T4. In the G group, normal saline was injected as control. After entry into the operation room (X0), before surgery (X1), 30 min after pneumoperitoneum (X2), 60 min after pneumoperitoneum (X3), 10 min after extubation (X4), the mean arterial pressure (MAP) and heart rate (HR) were recorded. The concentration of plasma endothelin (ET) and calcitonin gene-related peptide (CGRP) were detected. Meanwhile, isoflurane inhalation MAC and intervention situations were recorded. RESULTS: At X1-X3, MAP in the GE group was significantly lower than that in the G group (P < 0.05). At X2-X4 HR in two groups was significantly faster than at X1 (P < 0.05). At X4 HR in the GE group was significantly lower than that in the G group (P < 0.05). At X3 and X4, ET and CGRP were significantly lower than those in the G group (P < 0.05). At X2 and X3, ET in the GE group was significantly higher than that at X1 (P < 0.05). At X3, CGRP in the GE group was significantly higher than that at X1 (P < 0.05). At X2, X3 and before pneumoperitoneum, isoflurane MAC in the GE group was significantly lower than that in the G group (P < 0.05). At X2 and X3, isoflurane MAC in two groups was significantly higher than that during pneumoperitoneum (P < 0.05). CONCLUSION: Compared with general anesthesia, general anesthesia combined with epidural preemptive analgesia can effectively alleviate patients' stress reaction under retroperitoneal laparoscopic surgery.

Amitriptyline rather than lornoxicam ameliorates neuropathic pain-induced deficits in abilities of spatial learning and memory.

BACKGROUND AND OBJECTIVE: Clinical studies have revealed that patients with chronic pain are more likely to have anxiety and depression, which are often associated with cognitive dysfunction. However, whether neuropathic pain can induce cognition dysfunction remains uncertain. Antidepressants and nonsteroidal anti-inflammatory drugs can treat neuropathic pain, but whether they can prevent cognition dysfunction is unknown. The present study was designed to investigate the effects and possible mechanisms of neuropathic pain on learning and memory, and the effects of amitriptyline and lornoxicam on cognitive function. METHODS: Sixty male Sprague-Dawley rats were randomly subjected to L5 spinal nerve transection and sham operation, then given saline, amitriptyline and lornoxicam, respectively, during the postoperative days (7-28). Pain-related behaviours, depression-related behaviours, spatial learning and memory abilities, and expression of brain-derived neurotrophic factor were measured at different times after surgery. RESULTS: L5 spinal nerve transection induced mechanical allodynia and depression, and decreased the function of learning and memory as well as the expression of brain-derived neurotrophic factor. Amitriptyline ameliorated mechanical allodynia and depression-related behaviour, improved the impaired cognition, and increased the expression of brain-derived neurotrophic factor, whereas lornoxicam only inhibited the mechanical allodynia. CONCLUSIONS: We found that neuropathic pain may impair cognitive function via downregulation of the expression of brain-derived neurotrophic factor of the hippocampus, and amitriptyline rather than lornoxicam can ameliorate cognitive dysfunction via upregulation of brain-derived neurotrophic factor of the hippocampus.

Interaction of glia activation and neurotransmission in hippocampus of neuropathic rats treated with mirtazapine.

Recent studies have characterized a central nervous system neuroimmune effect in the analgesic mechanisms of antidepressants. Our study investigated the effect of a novel antidepressant mirtazapine on pro-inflammatory cytokines expression and astrocytic activation in hippocampus of neuropathic rats. L5 spinal nerve transection was made to produce mononeuropathic model. Mirtazapine was orally administered to rats that had been operated on daily for 14 days. Adrenergic or serotonergic receptor antagonist was intraperitoneally administered to examine their ability of blocking antinociceptive effect. In the region of hippocampus, TNFalpha and IL-1beta levels were assayed and the activity of astrocytes was immunostained with GFAP (glial fibrillary acidic protein) antibody. As a result, mirtazapine significantly inhibited the hyperalgesia produced by surgery, which was partially reversed by adrenergic and serotonergic antagonist. After surgery, the hippocampus demonstrated elevated TNFalpha and IL-1beta levels, concomitant with reactive astrocytes. Mirtazapine markedly reduced hippocampal cytokines production or astrocytic activation, which was blocked by both adrenergic and serotonergic antagonists. Our results indicate a possible role of hippocampal pro-inflammatory cytokines and glia in the pathogenesis of neuropathic pain. A potential analgesic mechanism of mirtazapine may be inhibiting the above neuroimmune action through affecting adrenergic and serotonergic system.

Effects of recombinant human erythropoietin on neuropathic pain and cerebral expressions of cytokines and nuclear factor-kappa B.

PURPOSE: The effect of recombinant human erythropoietin (rhEPO) on neuropathic pain remains unclear. This study aimed to determine the effects of preemptive administration of rhEPO on the behavioural changes and neuroinflammatory responses in a rat model of neuropathic pain. METHODS: Fifty rats were randomly allocated into five groups, sham-operation treated with saline and L5 spinal nerve transection treated with different doses of rhEPO (0 [saline], 1000, 3000, or 5000 U x kg(-1), respectively). The rats were intraperitoneally treated from 1 day before surgery to post-surgery day 7. The mechanical (paw pressure thresholds, PPT) and thermal thresholds (paw withdrawal latencies, PWL) were measured on post-surgery days 1, 3, and 7. The contralateral brain was obtained on post-surgery day 7 to determine the expressions of tumour necrosis factor (TNF-alpha), interleukin (IL)-1beta, IL-6, L-10, and nuclear factor-kappa B (NF-kappaB) activity. RESULTS: There were significant decreases in PPT and PWL after L5 spinal nerve transection (P < 0.001). Compared with the saline group, the rhEPO 3000 and 5000 U x kg(-1) groups resulted in significant increases in PPT and PWL (P < 0.001) and reduced the cerebral expressions of TNF-alpha, IL-1beta, IL-6, and NF-kappaB activity associated with the increase in IL-10 (rhEPO3000 group, P < 0.05, and rhEPO5000 group, P < 0.001, respectively). Administration of rhEPO 1000 U x kg(-1) had no significant effects on these variables. CONCLUSIONS: Preemptive rhEPO dose-dependently attenuated the mechanical and thermal hyperalgesia in L5 spinal nerve transection rats, which correlated with the decreased cerebral expressions of TNF-alpha, IL-1beta, and IL-6 via downregulating NF-kappaB activity and the increased expression of IL-10.

Comparison of vestibular function between large cerebellopontine angle meningioma and schwannoma.

CONCLUSION: Abnormal caloric and vestibular evoked myogenic potential (VEMP) responses are frequently encountered with a large cerebellopontine angle (CPA) schwannoma, while normal caloric responses and abnormal VEMPs are noted with a large CPA meningioma. This difference may possibly exist because schwannoma causes vestibular deficits via parenchymal involvement, while vestibular deficits in the meningioma are mostly due to compression neuropathy. OBJECTIVES: This study aimed to compare the tumor characteristics in relation to vestibular function, i.e. caloric and VEMP responses, between large-sized (>2.5 cm) meningioma and schwannoma in the CPA. PATIENTS AND METHODS: Five patients with large CPA meningioma and nine patients with large CPA schwannoma were enrolled in this study. Each patient underwent a battery of tests including audiometry, caloric test, VEMP test, and MRI study. RESULTS: The meningioma group showed 20% caloric abnormality and 75% VEMP abnormality, while the schwannoma group revealed 100% caloric and 100% VEMP abnormalities. A significant difference existed in relation to caloric abnormality between the two groups, but not in relation to VEMP abnormality.