Influencing factors and risk prediction model for emergence agitation after general anesthesia for primary liver cancer.

BACKGROUND: General anesthesia is commonly used in the surgical management of gastrointestinal tumors; however, it can lead to emergence agitation (EA). EA is a common complication associated with general anesthesia, often characterized by behaviors, such as crying, struggling, and involuntary limb movements in patients. If treatment is delayed, there is a risk of incision cracking and bleeding, which can significantly affect surgical outcomes. Therefore, having a proper understanding of the factors influencing the occurrence of EA and implementing early preventive measures may reduce the incidence of agitation during the recovery phase from general anesthesia, which is beneficial for improving patient prognosis. AIM: To analyze influencing factors and develop a risk prediction model for EA occurrence following general anesthesia for primary liver cancer. METHODS: Retrospective analysis of clinical data from 200 patients who underwent hepatoma resection under general anesthesia at Wenzhou Central Hospital (January 2020 to December 2023) was conducted. Post-surgery, the Richmond Agitation-Sedation Scale was used to evaluate EA presence, noting EA incidence after general anesthesia. Patients were categorized by EA presence postoperatively, and the influencing factors were analyzed using logistic regression. A nomogram-based risk prediction model was constructed and evaluated for differentiation and fit using receiver operating characteristics and calibration curves. RESULTS: EA occurred in 51 (25.5%) patients. Multivariate analysis identified advanced age, American Society of Anesthesiologists (ASA) grade III, indwelling catheter use, and postoperative pain as risk factors for EA (P < 0.05). Conversely, postoperative analgesia was a protective factor against EA (P < 0.05). The area under the curve of the nomogram was 0.972 [95% confidence interval (CI): 0.947-0.997] for the training set and 0.979 (95%CI: 0.951-1.000) for the test set. Hosmer-Lemeshow test showed a good fit (χ 2 = 5.483, P = 0.705), and calibration curves showed agreement between predicted and actual EA incidence. CONCLUSION: Age, ASA grade, catheter use, postoperative pain, and analgesia significantly influence EA occurrence. A nomogram constructed using these factors demonstrates strong predictive accuracy.

Product Selection Toward High-Value Hydrogen and Bamboo-Shaped Carbon Nanotubes from Plastic Waste by Catalytic Microwave Processing.

The escalating levels of plastic waste and energy crises underscore the urgent need for effective waste-to-energy strategies. This study focused on converting polypropylene wastes into high-value products employing various iron-based catalysts and microwave radiative thermal processing. The Al-Fe catalysts exhibited exceptional performance, achieving a hydrogen utilization efficiency of 97.65% and a yield of 44.07 mmol/g PP. The gas yields increased from 19.99 to 94.21 wt % compared to noncatalytic experiments. Furthermore, this catalytic system produced high-value bamboo-shaped carbon nanotubes that were absent in other catalysts. The mechanism analysis on catalytic properties and product yields highlighted the significance of oxygen vacancies in selecting high-value products through two adsorption pathways. Moreover, the investigation examined the variations in product distribution mechanisms between conventional and microwave pyrolysis, in which microwave conditions resulted in 4 times higher hydrogen yields. The technoeconomic assessment and Monte Carlo risk analysis further compared the disparity. The microwave technique had a remarkable internal rate of return (IRR) of 39%, leading to an income of $577/t of plastic with a short payback period of 2.5 years. This research offered sustainable solutions for the plastic crisis, validating the potential applicability of commercializing the research outcomes in real-world scenarios.

Surgical Excision Combined with Photodynamic Therapy for Squamous Cell Carcinoma Arising in Lupus Vulgaris.

Cutaneous squamous cell carcinoma (SCC) is a common non-melanoma skin cancer (NMSC). Although most cutaneous SCC in people with lighter skin pigmentation as a result of sun damage, patients with underlying conditions such as skin ulcers and chronic inflammation-including conditions such as lupus vulgaris (LV) and chronic discoid lupus erythematosus-are also predisposed to developing SCC. Here we report a case of secondary SCC diagnosed in a 54-year-old patient with 20 years of lupus vulgaris without prior formal systemic treatment, a rarity in clinical practice. Two months ago, the patient developed papules on the right cheek that ulcerated and discharged purulent fluid. Laboratory tests revealed a positive TSPOT result and histopathological examination confirmed granulomatous lesions, supporting the diagnosis of SLE. However, a tissue biopsy unexpectedly revealed a moderately differentiated SCC of the keratinizing type. In this case, we performed surgical excision of the lesion followed by cosmetic closure and adjuvant photodynamic therapy (PDT). Concurrently, the patient underwent systemic anti-tuberculosis treatment. At 6 months post-treatment, no tumour recurrence was observed and the rash associated with lupus erythematosus had also resolved. The patient was satisfied with the treatment outcome.

RT-RPA-PfAgo detection platform for one-tube simultaneous typing diagnosis of human respiratory syncytial virus.

Human respiratory syncytial virus (HRSV) is the most prevalent pathogen contributing to acute respiratory tract infections (ARTI) in infants and young children and can lead to significant financial and medical costs. Here, we developed a simultaneous, dual-gene and ultrasensitive detection system for typing HRSV within 60 minutes that needs only minimum laboratory support. Briefly, multiplex integrating reverse transcription-recombinase polymerase amplification (RT-RPA) was performed with viral RNA extracted from nasopharyngeal swabs as a template for the amplification of the specific regions of subtypes A (HRSVA) and B (HRSVB) of HRSV. Next, the Pyrococcus furiosus Argonaute (PfAgo) protein utilizes small 5'-phosphorylated DNA guides to cleave target sequences and produce fluorophore signals (FAM and ROX). Compared with the traditional gold standard (RT-qPCR) and direct immunofluorescence assay (DFA), this method has the additional advantages of easy operation, efficiency and sensitivity, with a limit of detection (LOD) of 1 copy/µL. In terms of clinical sample validation, the diagnostic accuracy of the method for determining the HRSVA and HRSVB infection was greater than 95%. This technique provides a reliable point-of-care (POC) testing for the diagnosis of HRSV-induced ARTI in children and for outbreak management, especially in resource-limited settings.

Intelligent electromagnetic navigation system for robot-assisted intraoral osteotomy in mandibular tumor resection: a model experiment.

Background: Mandibular tumor surgery necessitates precise osteotomies based on tumor boundaries; however, conventional osteotomies often lack accuracy in predicting osteotomy positions and planes, potentially leading to excessive resection of normal bone tissues or residual tumors, thus compromising postoperative quality of life and clinical outcomes. Robotic-assisted surgery (RAS) augmented with artificial intelligence (AI) offers precise localization capabilities, aiding surgeons in achieving accurate osteotomy positioning. This study aimed to evaluate the feasibility and accuracy of a robotic magnetic navigation system for positioning and osteotomy in an intraoral surgical trial of a mandibular tumor model. Methods: Patient computed tomography (CT) imaging data of mandibular chin and body tumors were utilized to create 3D printed models, serving as study subjects for mandibular tumor resection. Ten pairs of models were printed for the experimental and control groups. The experimental group (EG) underwent osteotomy using a robot-assisted surgical navigation system, performing osteotomy under robotic navigation following alignment based on preoperative design. The control group (CG) underwent traditional surgery, estimating osteotomy position empirically according to preoperative design. Postoperative CT scans were conducted on both models, and actual postoperative results were compared to preoperative design. Osteotomy accuracy was evaluated by positional and angular errors between preoperatively designed and actual osteotomy planes. Results: For ten randomly selected spots on the left and right sides, respectively, the EG group had mean distance errors of 0.338 mm and 0.941 mm. These values were obtained from the EG group. In the EG group, on the left side, the mean angular errors were 14.741 degrees, while on the right side, they were 13.021 degrees. For the 10 randomly selected spots on the left and right sides, respectively, the CG had mean distance errors of 1.776 mm and 2.320 mm. This is in contrast to the results obtained by the EG. It was determined that the left side had a mean angle error of 16.841 degrees, while the right side had an error of 18.416 degrees in the CG group. The above results indicated significantly lower point errors of bilateral osteotomy planes in the experimental group compared to the control group. Conclusion: This study demonstrates the feasibility of electromagnetic navigation robot-assisted intraoral osteotomy for mandibular tumors and suggests that this approach can enhance the precision of clinical surgery.

Remote self-report and speech-in-noise measures predict clinical audiometric thresholds.

OBJECTIVE: Developments in smartphone technology and the COVID-19 pandemic have highlighted the feasibility and need for remote, but reliable hearing tests. Previous studies used remote testing but did not directly compare results in the same listeners with standard lab or clinic testing. This study investigated validity and reliability of remote, self-administered digits-in-noise (remote-DIN) compared with lab-based, supervised (lab-DIN) testing. Predictive validity was further examined in relation to a commonly used self-report, Speech, Spatial, and Qualities of Hearing (SSQ-12), and lab-based, pure tone audiometry. DESIGN: DIN speech reception thresholds (SRTs) of adults (18-64 y/o) with normal hearing (NH, N = 16) and hearing loss (HL, N = 18), were measured using English-language digits (0-9), binaurally presented as triplets in one of four speech-shaped noise maskers (broadband, low-pass filtered at 2, 4, 8 kHz) and two phases (diotic, antiphasic). RESULTS: High, significant intraclass correlation coefficients indicated strong internal consistency of remote-DIN SRTs, which also correlated significantly with lab-DIN SRTs. There was no significant mean difference between remote- and lab-DIN on any tests. NH listeners had significantly higher SSQ scores and remote- and lab-DIN SRTs than listeners with HL. All versions of remote-DIN SRTs correlated significantly with pure-tone-average (PTA), with the 2-kHz filtered test being the best predictor, explaining 50% of the variance in PTA. SSQ total score also significantly and independently predicted PTA (17% of variance) and all test versions of the remote-DIN, except the antiphasic BB test. CONCLUSIONS: This study underscores the effectiveness of remote DIN test and SSQ-12 in assessing auditory function. These findings suggest the potential for wider access to reliable hearing assessment, particularly in remote or underserved communities.

Cyclododecane-based high-intactness and clean transfer method for fabricating suspended two-dimensional materials.

The high-intactness and ultraclean fabrication of suspended 2D materials has always been a challenge due to their atomically thin nature. Here, we present a universal polymer-free transfer approach for fabricating suspended 2D materials by using volatile micro-molecule cyclododecane as the transfer medium, thus ensuring the ultraclean and intact surface of suspended 2D materials. For the fabricated monolayer suspended graphene, the intactness reaches 99% for size below 10 µm and suspended size reaches 36 µm. Owing to the advantages of ultra-cleanness and large size, the thermal conductivity reaches 4914 W m - 1 K - 1 at 338 K. Moreover, this strategy can also realize efficient batch transfer of suspended graphene and is applicable for fabricating other 2D suspended materials such as MoS2. Our research not only establishes foundation for potential applications and investigations of intrinsic properties of large-area suspended 2D materials, but also accelerates the wide applications of suspended graphene grid in ultrahigh-resolution TEM characterization.

Identification of a Novel ECM Remodeling Macrophage Subset in AKI to CKD Transition by Integrative Spatial and Single-Cell Analysis.

The transition from acute kidney injury (AKI) to chronic kidney disease (CKD) is a critical clinical issue. Although previous studies have suggested macrophages as a key player in promoting inflammation and fibrosis during this transition, the heterogeneity and dynamic characterization of macrophages are still poorly understood. Here, we used integrated single-cell RNA sequencing and spatial transcriptomic to characterize the spatiotemporal heterogeneity of macrophages in murine AKI-to-CKD model of unilateral ischemia-reperfusion injury. A marked increase in macrophage infiltration at day 1 was followed by a second peak at day 14 post AKI. Spatiotemporal profiling revealed that injured tubules and macrophages co-localized early after AKI, whereas in late chronic stages had spatial proximity to fibroblasts. Further pseudotime analysis revealed two distinct lineages of macrophages in this transition: renal resident macrophages differentiated into the pro-repair subsets, whereas infiltrating monocyte-derived macrophages contributed to chronic inflammation and fibrosis. A novel macrophage subset, extracellular matrix remodeling-associated macrophages (EAMs) originating from monocytes, linked to renal fibrogenesis and communicated with fibroblasts via insulin-like growth factors (IGF) signalling. In sum, our study identified the spatiotemporal dynamics of macrophage heterogeneity with a unique subset of EAMs in AKI-to-CKD transition, which could be a potential therapeutic target for preventing CKD development.

Exercise effects on brain health and learning from minutes to months: The brain EXTEND trial.

Despite evidence that aerobic exercise benefits the aging brain, in particular the hippocampus and memory, controlled clinical trials have not comprehensively evaluated effects of aerobic exercise training on human memory in older adults. The central goal of this study was to determine chronic effects of moderate-to-vigorous intensity aerobic exercise on the hippocampus and memory in non-demented, inactive adults ages 55-80 years. We determine effects of aerobic exercise training with a 6-month randomized controlled trial (RCT) comparing 150 min/week of home-based, light intensity exercise with progressive moderate-to-vigorous intensity aerobic exercise. For the first time in a large trial, we examined temporal mechanisms by determining if individual differences in the rapid, immediate effects of moderate intensity exercise on hippocampal-cortical connectivity predict chronic training-related changes over months in connectivity and memory. We examined physiological mechanisms by testing the extent to which chronic training-related changes in cardiorespiratory fitness are a critical factor to memory benefits. The Exercise Effects on Brain Connectivity and Learning from Minutes to Months (Brain-EXTEND) trial is conceptually innovative with advanced measures of hippocampal-dependent learning and memory processes combined with novel capture of the physiological changes, genetic components, and molecular changes induced by aerobic exercise that change hippocampal-cortical connectivity. Given that hippocampal connectivity deteriorates with Alzheimer's and aerobic exercise may contribute to reduced risk of Alzheimer's, our results could lead to an understanding of the physiological mechanisms and moderators by which aerobic exercise reduces risk of this devastating and costly disease.

Application of Reducible Covalent Capture Purification for Resolving Persulfidome and Nucleolin S-Sulfhydration.

Protein S-sulfhydration involves the regulation of various protein functions, and resolving the S-sulfhydrated proteome (persulfidome) allows for a deeper exploration of various redox regulations. Therefore, we designed a reducible covalent capture method for isolating S-sulfhydrated proteins, which can analyze the persulfidome in biological samples and monitor specific S-sulfhydrated proteins. In this study, we applied this method to reveal the S-sulfhydration levels of proteins, including 3-phosphoglyceraldehyde dehydrogenase, NFκB/p65, and nucleolin. Furthermore, this technique can be used to enrich S-sulfhydrated peptides, aiding in the determination of protein S-sulfhydration modification sites. Finally, we observed that the S-sulfhydration and oxidation of nucleolin on the C543 residue correlate with its nuclear translocation, downstream regulation of p53, Bcl-xL, and Bcl-2 RNA levels and protein expression, as well as the protective function against oxidative stress. Therefore, this method may facilitate the understanding of the regulation of protein function by redox perturbation.

Effects of world stroke campaign on stroke literacy and knowledge in Taiwan.

OBJECTIVES: Stroke is a leading cause of death in Taiwan. Poor public knowledge of stroke may lead to delays in prehospital arrival, resulting in unfavorable prognoses. Studies have investigated public knowledge of stroke and highlighted the importance of stroke education, however, few such studies have been conducted in Taiwan. This study assessed the changes in public knowledge of stroke between 2012 and 2020 by conducting a survey during two World Stroke Day events. Furthermore, this study identified areas where educational efforts may have been insufficient. MATERIALS & METHODS: Questionnaires were distributed to the participants of 2012 and 2020 World Stroke Day events in Taiwan. In total, 328 and 336 questionnaires were completed, respectively. Stroke literacy and knowledge were analyzed between 2012 and 2020. Data were analyzed using the chi-square test or independent t-test. p < 0.05 indicates statistical significance. RESULTS: Hypertension was the most recognized risk factor for stroke in both years (p < 0.001), and recognition of most of the given risk factors significantly increased. In addition, recognition of more than half of the stroke warning signs significantly increased, awareness of the correct acute stroke response also increased (p < 0.001), and overall stroke literacy in Taiwan increased (p = 0.001). CONCLUSION: Stroke literacy and knowledge in Taiwan have improved significantly between 2012 and 2020, but many people still lack adequate stroke knowledge and awareness. Government health department must take this sort of intervention continually (campaigns) and novel approaches (e.g. board game…) to improve stroke literacy and knowledge in public health. REGISTRATION ID: N202109072, approved by the Joint Institutional Review Board of Taipei Medical University on 2021/11/02.

A radiogenomic clinical decision support system to inform individualized treatment in advanced nasopharyngeal carcinoma.

Both concurrent chemoradiotherapy (CCRT) and induction chemotherapy (ICT) followed by CCRT are standard care of advanced nasopharyngeal carcinoma (NPC). However, tailoring personalized treatment is lacking. Herein, we established a radiogenomic clinical decision support system to classify patients into three subgroups according to their predicted disease-free survival (DFS) with CCRT and ICT response. The CCRT-preferred group was suitable for CCRT since they achieved good survival with CCRT, which could not be improved by ICT. The ICT-preferred group was suitable for ICT plus CCRT since they had poor survival with CCRT; additional ICT could afford an improved DFS. The clinical trial-preferred group was suitable for clinical trials since they exhibited poor survival regardless of receiving CCRT or ICT plus CCRT. These findings suggest that our radiogenomic clinical decision support system could identify optimal candidates for CCRT, ICT plus CCRT, and clinical trials, and may thus aid in personalized management of advanced NPC.

Primary mucinous adenocarcinoma of the anterior mediastinum with HER-2 mutation: A rare case report.

We report the case of a 68-year-old male whose Computed Tomography (CT) scan presented a mass (68*62*54 mm) of the right anterior mediastinal and pathologically diagnosis was mucinous adenocarcinoma(MA). The peripheral vessels are surrounded by the big mass in the anterior mediastinum which was associated with multiple metastases, thus we performed palliative chemoradiotherapy and we tried Human Epidermal Growth Factor Receptor-2 (HER-2) inhibitors based on the Next Generation Sequencing. The patient passed away 16 months after the onset of the disease. In this report, we review the rare case of anterior mediastinum MA as well as perspectives for potential future treatments.

Post-marketing safety concerns with relugolix: a disproportionality analysis of the FDA adverse event reporting system.

BACKGROUND: Relugolix has been used to treat advanced prostate cancer. This study assessed adverse events (AEs) associated with relugolix from the US Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS: Disproportionality analysis, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms, were employed to quantify the signals of relugolix-associated AEs. RESULTS: A total of 5,059,213 reports of AEs were collected from the FAERS database, of which 5,662 reports were identified with relugolix as the "primary suspect (PS)". A total of 70 significant disproportionality PTs conforming to the four algorithms were simultaneously retained. Unexpected new AEs, such as erectile dysfunction, gynaecomastia, testicular atrophy, male genital atrophy, libido decreased might also occur. CONCLUSION: This study found potential new AEs signals and might provide important support for clinical monitoring and risk identification of relugolix.

First Report of Mango Stem-end Rot Caused by Pestalotiopsis kenyana in Yunnan Province, China.

Stem End Rot (SER) is a devastating post-harvest disease of mango fruits causing severe losses during storage. In 22 July 2023, 31 out of 50 intact mangoes (cv. Sensation) collected from five orchards in Huaping county (26°37'N 101°15') showed typical symptoms of SER after stored for 9 d in room temperature (24-28℃). Initially, small dark brown to black spots appeared around the fruit peduncle, which rapidly expanded through the pulp tissues. The symptomatic mangoes were surface disinfected by 3% NaClO for 30 s after soaking in 75% alcohol for 3 min, and cleaned by sterile water for 3 times. Tissues were cut from the edge of lesions, dried by sterile filter paper, transferred to PDA and cultured at 28 ℃ for 5 d (Tovar-Pedraza et al., 2020). The single-spore isolation method was used to obtain pure culture. Thirty eight isolates presented four distinct kind of morphology on PDA medium. Among them, 11 isolates with same morphology were significantly distinct from common pathogens of SER. The colonies were white and pale yellow on reverse side. Mycelia grew fast and reached the edge of 90 mm Petri dish after cultured for 5d. Pycnidia were black and scattered on the mycelial mats after 15-20 d. Conidia were fusoid, straight to slightly curved, four septa, and brown. Pigmented median cells doliiform, 14.97 - 18.62(16.11 ±0.89)×5.61- 7.28 (6.61±0.51) µm. Apical cell hyaline, subcylindrical; 1-3 tubular transparent apical appendages 12.27 - 16.68 (13.65±3.78)×1.14 - 1.99 (1.59±0.36) µm. Basal cell conical with a truncate base, hyaline, and 1-2 tubulose basal appendages with 2.85 - 7.97 (5.18±1.88)×0.99 - 1.85 (1.38±0.29) µm (n=50). These fungi were described as Pestalotiopsis kenyana. based on morphological characters (Maharachchikumbura et al., 2014) which were different from isolates characterized as other common SER pathogens (Botryosphaeria, Neofusicoccum). Based on morphology, HPSX-4 was selected for further identification. ITS region, tef1-α, ß-tub of HPSX-4 were amplified and sequenced (Xun et al., 2023). The sequences were deposited in GenBank (ITS:OR889126, tef1-α:OR913431, ß-tub: OR913432). The ITS, tef1-α, ß-tub sequence of HPSX-4 showed 100% (525/525)，99.59% (241/242), and 100% (742/742) identity to the P. kenyana CBS442.67 sequences (ITS: NR147549，tef1-α: KM199502, ß-tub: KM199395), respectively. HPSX-4 clustered with P. kenyana CBS 442.67 (type strain) based on maximum likelihood method by MEGA 7.0.21(Minh et al., 2013). Pathogenicity test was performed on 12 healthy mangoes (cv. Golek) by placing mycelial plugs around the peduncle and the middle of the fruit by pin-prick method according to Feng et al.(2023). Sterile PDA were used as control (three mangoes). Every inoculated fruit was incubated at 28°C, 95% ± 3% humidity with three replicates for each treatment. The experiment was repeated three times. Typical symptoms of SER were observed. There were no symptoms in the control group. The strain was reisolated and identified as P. kenyana with the method mentioned above which fulfilled Koch's postulates. This is the first report of P. kenyana causing SER disease on Mangifera indica L.. This study expands our understanding of the pathogen range of mango SER which conducive to prevent and control the SER caused by P. kenyana.

A rare family outbreak of Mycobacterium abscessus infection in immunocompetent fraternal triplets.

Background: Mycobacterium abscessus (M. abscessus) infection is rare in children who were previously healthy, particularly in infants. We present the first report of a family outbreak of M. abscessus infection among immunocompetent infant triplets. Methods: We reviewed triplets' demographic data, laboratory tests and imaging examinations to describe their clinical features. We performed whole-exome sequencing to rule out primary immunodeficiency disorders. We used DNA sequencing for M. abscessus subspecies identification. Results: The fraternal triplets (triples A, B and C) presented with a 10-day history of cough. Triple A also experienced a brief episode of fever, and triple B had tachypnea. Chest CT scans showed pulmonary masses and nodules in triples A and C, and cavities in triple B. Cultures of sputum and bronchoalveolar lavage fluid from all triplets yielded M. abscessus. Further subspecies identification showed that isolates from triples A and C were M. abscessus subsp. massiliense, and isolates from triple B were M. abscessus subsp. abscessus (MAA). After eight months of combination therapy, the pulmonary lesions of the triplets improved significantly. Conclusion: Our study confirms that M. abscessus pulmonary disease can occur in immunocompetent infants. We hypothesize that the simultaneous infection of the triplets may be associated with their prematurity and extensive environmental exposure. This study highlights the importance to include M. abscessus infection in the differential diagnosis of pulmonary masses and/or cavities, regardless of the age of onset or the presence of underlying pathology or susceptible genes.

Hepatoid adenocarcinoma of the lung: A case report.

BACKGROUND: Hepatoid adenocarcinoma of the lung (HAL) is a rare type of non-small cell lung cancer (NSCLC), histologically similar to hepatocellular carcinoma. HAL has high malignancy and poor prognosis, and a better treatment plan needs further study. CASE SUMMARY: In order to deeply understand the occurrence and development of HAL, here we report a case of HAL with extensive metastasis of alpha fetoprotein negative KRAS A146T mutation. The patient refused chemotherapy and received one course of treatment (immune checkpoint inhibitors), and died three months later due to progressive disease. CONCLUSION: HAL is a special type of NSCLC. The surgical treatment of HAL in the limited stage can achieve long-term survival, but most of them were in the advanced stage when they were found, and the prognosis was poor, which requires multidisciplinary comprehensive treatment.

Ginsenoside Rg1 inhibits multiple myeloma and overcomes bortezomib resistance through AMPK-mTOR pathway.

Background: The resistance of multiple myeloma (MM) to bortezomib (BTZ) has brought multiple challenges to its clinical use. Numerous ginsenosides have potential anti-tumor effects, however, the research on the role of Rg1 in MM has not been reported. Objective: To examine the inhibitory impact of Rg1 on the growth of MM and reduce the drug resistance of MM to BTZ through in vivo and in vitro experiments, and to explore their potential mechanism. Methods: BTZ drug-resistant cell line RPMI8226R was constructed. Mouse tumor-bearing model was developed by abdominal subcutaneous injection of MM cells. MM cells were treated with AMPK inhibitor Compound C or autophagy inhibitor Chloroquine together with Rg1. RPMI8226R cells were treated with BTZ and Rg1. Cell multiplication was detected using Methylthiazolyldiphenyl-tetrazolium bromide assay. Apoptosis was assessed using flow cytometry. Immunofluorescence assay was employed to assess the autophagy markers LC3. Western blot was utilized to assess the protein expression. Immunohistochemistry was used to detect cell proliferation and apoptosis in tumor tissues. Results: In vitro experiments demonstrated that Rg1 could hinder the proliferation of MM cells, promote apoptosis and enhance autophagy. Rg1 could also increase the sensitivity of RPMI8226R to BTZ. In vivo experiments illustrated that Rg1 could hinder the development of MM cells in mice, weaken the proliferation of tumor cells and enhance their apoptosis. Further study found that the anti-MM impact of Rg1 was linked to AMPK-mTOR pathway, the autophagy degree of RPMI8226R was higher than that of RPMI8226, and that Rg1 could inhibit MM and overcome drug resistance through autophagy induced by AMPK-mTOR pathway. Conclusion: Rg1 has significant anti-MM effect and can overcome BTZ resistance, and its potential mechanism is related to the regulation of autophagy induced by AMPK-mTOR pathway. Rg1 is a promising adjuvant drug for the treatment of MM.

A pedigree analysis of Rotor hyperbilirubinemia combined with hepatitis B virus infection in a SLCO1B1 and SLCO1B3 gene mutations patient.

Background: Rotor syndrome (RS, OMIM#237450) is an extremely rare autosomal digenic recessive disorder characterized by mild non-hemolytic hereditary conjugated hyperbilirubinemia, caused by biallelic variation of SLCO1B1 and SLCO1B3 genes that resulted in OATP1B1/B3 dysfunction in the sinusoidal membrane leading to impaired bilirubin reuptake ability of hepatocytes. Methods: One RS pedigree was recruited and clinical features were documented. Whole genome second-generation sequencing was used to screen candidate genes and mutations, Sanger sequencing confirmed predicted mutations. Results: This study detected a homozygous nonsense variant c.1738C > T (p.R580*) in the coding region of the SLCO1B1 (NM006446) gene in a family with RS and hepatitis B virus infection by Variants analysis and Sanger sequencing, and confirmed by Copy Number Variation (CNV) analysis and Long Range PCR that there was a homozygous insertion of intron 5 of the SLCO1B3 gene into intron 5 of long-interspersed element 1 (LINE1). A few cases of such haplotypes have been reported in East Asian populations. A hepatitis B virus infection with fatty liver disease was indicated by pathology, which revealed mild-moderate lobular inflammation, moderate lobular inflammation, moderate hepatocellular steatosis, and fibrosis stage 1-2 (NAS score: 4 points/S1-2) alterations. Heterozygotes carrying p.R580* and LINE1 insertions were also detected in family members (I1, I2, III2, III3), but they did not develop conjugated hyperbilirubinemia. Conclusion: The mutations may be the molecular genetic foundation for the presence of SLCO1B1 c.1738C > T(p.R580*) and SLCO1B3 (LINE1) in this RS pedigree.

Enhancing Sugarcane Seedling Resilience to Water Stress through Exogenous Abscisic Acid: A Study on Antioxidant Enzymes and Phytohormone Dynamics.

Exogenous hormones play a crucial role in regulating plant growth, development, and stress tolerance. However, the effects of exogenous abscisic acid (ABA) on sugarcane seedlings under water stress remain poorly understood. Here, in this study, a pot experiment was conducted on sugarcane seedlings 4 weeks after transplanting, employing three treatments: control (normal growth), drought (water stress), and drought + ABA (foliar application of 100 µM ABA before water stress). The main objectives of this research are to understand the effects of exogenous ABA on sugarcane seedlings under water stress conditions and to assess the changes in antioxidant enzyme activity and phytohormone levels in response to exogenous ABA. Water stress was induced in the solution culture by adding 25% (w/v) polyethylene glycol (PEG) 6000 to the Hoagland solution. Leaf samples were collected at 3, 6, and 9 days after treatment, and the photosynthetic and biochemical responses of ABA-treated plants to drought stress were investigated. The indole acetic acid (IAA) activity of the ABA-treated drought plants is compared to that of drought plants. Moreover, the endogenous ABA levels of the ABA-treated drought plants were significantly enhanced by 42.2, 39.9, and 42.3% at 3, 6, and 9 days, respectively, compared to those of drought plants. Additionally, the proline content of the ABA-treated drought plants significantly increased by 45 and 80% at 6 and 9 days, respectively, compared to that of drought plants. The expression of the catalase 1 (CAT1) gene was increased in the ABA-treated drought plants by 2.1-fold, 0.7-fold, and 1.37-fold at 3, 6, and 9 days, respectively, compared to that in drought plants. Similarly, the expression of superoxide dismutase, peroxidase, and ascorbate peroxidase genes of the ABA-treated drought plants also increased compared to those of the drought plants. In conclusion, foliar application of ABA mitigated the negative effects of water shortage of sugarcane plants under water stress. Applying ABA improved the antioxidant defense system of sugarcane plants under drought stress, thereby enhancing their photosynthetic activities and productivity.