Super enhancer acquisition drives expression of oncogenic PPP1R15B that regulates protein homeostasis in multiple myeloma.

Multiple myeloma is a hematological malignancy arising from immunoglobulin-secreting plasma cells. It remains poorly understood how chromatin rewiring of regulatory elements contributes to tumorigenesis and therapy resistance in myeloma. Here we generate a high-resolution contact map of myeloma-associated super-enhancers by integrating H3K27ac ChIP-seq and HiChIP from myeloma cell lines, patient-derived myeloma cells and normal plasma cells. Our comprehensive transcriptomic and phenomic analyses prioritize candidate genes with biological and clinical implications in myeloma. We show that myeloma cells frequently acquire SE that transcriptionally activate an oncogene PPP1R15B, which encodes a regulatory subunit of the holophosphatase complex that dephosphorylates translation initiation factor eIF2α. Epigenetic silencing or knockdown of PPP1R15B activates pro-apoptotic eIF2α-ATF4-CHOP pathway, while inhibiting protein synthesis and immunoglobulin production. Pharmacological inhibition of PPP1R15B using Raphin1 potentiates the anti-myeloma effect of bortezomib. Our study reveals that myeloma cells are vulnerable to perturbation of PPP1R15B-dependent protein homeostasis, highlighting a promising therapeutic strategy.

solid volume ratio in predicting pathological features of cT1 lung adenocarcinoma.

BACKGROUND: More effective methods are urgently needed for predicting the pathological grade and lymph node metastasis of cT1-stage lung adenocarcinoma. METHODS: We analyzed the relationships between CT quantitative parameters (including three-dimensional parameters) and pathological grade and lymph node metastasis in cT1-stage lung adenocarcinoma patients of our center between January 2015 and December 2023. RESULTS: A total of 343 patients were included, of which there were 233 males and 110 females, aged 61.8 ± 9.4 (30-82) years. The area under the receiver operating characteristic (ROC) curve for predicting the pathological grade of lung adenocarcinoma using the consolidation tumor ratio (CTR) and the solid volume ratio (SVR) were 0.761 and 0.777, respectively. The areas under the ROC curves (AUCs) for predicting lymph node metastasis were 0.804 and 0.873, respectively. Multivariate logistic regression analysis suggested that the SVR is an independent predictor of highly malignant lung adenocarcinoma pathology, while the SVR and pathological grade are independent predictors of lymph node metastasis. The sensitivity of predicting the pathological grading of lung adenocarcinoma based on SVR>5% is 97.2%, with a negative predictive value of 96%. The sensitivity of predicting lymph node metastasis based on SVR>47.1% is 97.3%, and the negative predictive value is 99.5%. CONCLUSIONS: The SVR has greater diagnostic value than the CTR in the preoperative prediction of pathologic grade and lymph node metastasis in stage cT1-stage lung adenocarcinoma patients, and the SVR may replace the diameter and CTR as better criteria for guiding surgical implementation.

Assessing Stroke Recurrence Risk by Using a Lipoprotein-Associated Phospholipase A2 and Platelet Count-Based Nomogram.

Stroke recurrence remains a critical challenge in clinical neurology, necessitating the identification of reliable predictive markers for better management and treatment strategies. This study investigates the interaction between lipoprotein-associated phospholipase A2 (Lp-PLA2) and platelets as a potential predictor for stroke recurrence, aiming to refine risk assessment and therapeutic approaches. In a retrospective cohort of 580 ischemic stroke patients, we analyzed clinical data with a focus on Lp-PLA2 and platelet levels. By using multivariable logistic regression, we identified independent predictors of stroke recurrence. These predictors were then used to develop a comprehensive nomogram. The study established diabetes mellitus, hypertension, low-density lipoprotein (LDL), Lp-PLA2 levels, and platelet counts as independent predictors of stroke recurrence. Crucially, the interaction parameter Lp-PLA2 * platelet (multiplication of Lp-PLA2 and platelet count) exhibited superior predictive power over each factor considered separately. Our nomogram incorporated diabetes mellitus, cerebral infarction causes, hypertension, LDL, and the Lp-PLA2 * platelet count interaction and demonstrated enhanced accuracy in predicting stroke recurrence compared to traditional risk models. The interaction between Lp-PLA2 and platelets emerged as a significant predictor for stroke recurrence when integrated with traditional risk factors. The developed nomogram offers a novel and practical tool in molecular neurobiology for assessing individual risks, facilitating personalized treatment strategies. This approach underscores the importance of multifactorial assessment in stroke management and opens avenues for targeted interventions to mitigate recurrence risks.

A noble metal-enhanced Au@CuO heterostructure with multienzyme-mimicking activities for colorimetric detection of tannic acid.

Nanozymes, serving as synthetic alternatives to natural enzymes, offer several benefits including cost-effectiveness, enzyme-like catalytic abilities, enhanced stability, adjustable catalytic activity, easy recyclability, mild reaction conditions, and environmental friendliness. Nonetheless, the ongoing quest to develop nanozymes with enhanced activity and to delve into the catalytic mechanism remains a challenge. In our research, we effectively developed Au@CuO nanocomposites (Au@CuO Nc), replicating the functions of four enzymes found in nature: peroxidase (POD), catalase (CAT), glutathione peroxidase (GPx), and oxidase (OXD). The catalytic efficiency of Au@CuO Nc for TMB oxidation (oxTMB) was approximately 4.8 times greater than that of plain Cu2O cubes, attributed to the synergistic catalytic impact between the Au element and Cu2O within Au@CuO Nc. Mechanistic studies revealed that the novel Au@CuO Nc nanozyme greatly enhances the decomposition of H2O2 to reactive oxygen species (ROS) intermediates (˙OH, ˙O2- and 1O2), resulting in increased POD-like activity of the single-component Cu2O cubes. When an antioxidant like TA was added to the chromogenic system, it converted oxTMB into a colorless form of TMB, enabling further evaluation of TA. Hence, a colorimetric sensor was developed for the rapid and precise quantitative measurement of TA, demonstrating strong linearity between 0.3 and 2.4 µM and featuring a low detection threshold of 0.25 µM. Moreover, this sensor was effectively utilized for the assessment of TA in actual tea samples. This work innovatively proposes a simplified and reliable strategy for the advanced design of highly effective Cu-based nanozymes, enhancing enzyme-like reactions for simultaneous, on-site colorimetric probing of antioxidants.

Robotic-assisted low anterior resection for rectal cancer shows similar clinical efficacy to laparoscopic surgery: A propensity score matched study.

BACKGROUND: Rectal cancer ranks as the second leading cause of cancer-related mortality worldwide, necessitating surgical resection as the sole treatment option. Over the years, there has been a growing adoption of minimally invasive surgical techniques such as robotic and laparoscopic approaches. Robotic surgery represents an innovative modality that effectively addresses the limitations associated with traditional laparoscopic techniques. While previous studies have reported favorable perioperative outcomes for robot-assisted radical resection in rectal cancer patients, further evidence regarding its oncological safety is still warranted. AIM: To conduct a comparative analysis of perioperative and oncological outcomes between robot-assisted and laparoscopic-assisted low anterior resection (LALAR) procedures. METHODS: The clinical data of 125 patients who underwent robot-assisted low anterior resection (RALAR) and 279 patients who underwent LALAR resection at Shandong Provincial Hospital Affiliated to Shandong First Medical University from December 2019 to November 2022 were retrospectively analyzed. After performing a 1:1 propensity score matching, the patients were divided into two groups: The RALAR group and the LALAR group (111 cases in each group). Subsequently, a comparison was made between the short-term outcomes within 30 d after surgery and the 3-year survival outcomes of these two groups. RESULTS: Compared to the LALAR group, the RALAR group exhibited a significantly earlier time to first flatus [2 (2-2) d vs 3 (3-3) d, P = 0.000], as well as a shorter time to first fluid diet [4 (3-4) d vs 5 (4-6) d, P = 0.001]. Additionally, the RALAR group demonstrated reduced postoperative indwelling catheter time [2 (1-3) d vs 4 (3-5) d, P = 0.000] and decreased length of hospital stay after surgery [5 (5-7) d vs 7(6-8) d, P = 0.009]. Moreover, there was an observed increase in total cost of hospitalization for the RALAR group compared to the LALAR group [10777 (10780-11850) dollars vs 10550 (8766-11715) dollars, P = 0.012]. No significant differences were found in terms of conversion rate to laparotomy or incidence of postoperative complications between both groups. Furthermore, no significant disparities were noted regarding the 3-year overall survival rate and 3-year disease-free survival rate between both groups. CONCLUSION: Robotic surgery offers potential advantages in terms of accelerated recovery of gastrointestinal and urologic function compared to LALAR resection, while maintaining similar perioperative and 3-year oncological outcomes.

Engineering Tough Supramolecular Hydrogels with Structured Micropillars for Tunable Wetting and Adhesion Properties.

Soft-lithography is widely used to fabricate microstructured surfaces on plastics and elastomers for designable physical properties such as wetting and adhesions. However, it remains a big challenge to construct high-aspect-ratio microstructures on the surface of hydrogels due to the difficulty in demolding from the gel with low strength and stiffness. Demonstrated here is the engineering of tough hydrogels by soft-lithography to form well-defined micropillars. The mechanical properties of poly(acrylamide-co-methacrylic acid) hydrogels with dense hydrogen-bond associations severely depend on temperature, with Young's modulus increasing from 8.1 MPa at 15 °C to 821.8 MPa at -30 °C, enabling easy demolding at low temperatures. Arrays of micropillars are maintained on the surface of the gel, and can be used at room temperature when the gel restores soft and stretchable. The hydrogel also exhibits good shape-memory property, favoring tailoring the morphology with a switchable tilt angle of micropillars. Consequently, the hydrogel shows tunable wetting and adhesion properties, as manifested by varying contact angles and adhesion strengths. These surface properties can also be tuned by geometry and arrangement of micropillars. This facile strategy by harnessing tunable viscoelasticity of supramolecular hydrogels should be applicable to other soft materials, and broaden their applications in biomedical and engineering fields.

A preliminary study of modified inflatable mediastinoscopic and single-incision plus one-port laparoscopic esophagectomy.

Background: Esophageal malignancies have a high morbidity rate worldwide, and minimally invasive surgery has emerged as the primary approach for treating esophageal cancer. In recent years, there has been increasing discussion about the potential of employing inflatable mediastinoscopic and laparoscopic approaches as an option for esophagectomy. Building on the primary modification of the inflatable mediastinoscopic technique, we introduced a secondary modification to further minimize surgical trauma. Methods: We conducted a retrospective analysis of patients who underwent inflatable mediastinoscopy combined with laparoscopic esophagectomy at the Second Affiliated Hospital of Naval Medical University from March 2020 to March 2023. The patients were allocated to the following two groups: the traditional (primary modification) group, and the secondary modification group. Operation times, intraoperative bleeding, and postoperative complications were compared between the groups. Results: The procedure was successfully performed in all patients, and conversion to open surgery was not required in any case. There were no statistically significant differences in the surgical operation time, intraoperative bleeding, number of dissected lymph nodes, and rate of postoperative anastomotic leakage between the two groups. However, a statistically significant difference was observed in the length of the mobilized esophagus between the two groups. The mobilization of esophagus to the level of diaphragmatic hiatus via the cervical incision was successfully achieved in more patients in the secondary modification group than the primary modification group. Conclusions: Inflatable mediastinoscopy combined with single-incision plus one-port laparoscopic esophagectomy is a safe and effective surgical procedure. The use of a 5-mm flexible endoscope, ultra-long five-leaf forceps, and LigaSure Maryland forceps facilitates esophageal mobilization and lymph node dissection through a single cervical incision.

Comparison of psoas major activation during standing hip flexion between chronic low back pain and healthy populations.

BACKGROUND: The psoas major (PM) has been identified as a potential contributor to chronic low back pain (LBP). However, few studies have investigated the effects of upright functional movement on PM activation in cLBP individuals. OBJECTIVE: This cross-sectional study aims to compare PM muscle activation characteristics in chronic LBP (cLBP) and healthy subjects during the transition from quiet double-leg standing to standing hip flexion. METHODS: Ultrasound Imaging was used to assess PM thickness at the lumbar vertebral level of L4-5 in 12 healthy and 12 cLBP participants. The changes in thickness between the test positions were utilized as a proxy for PM activation. RESULTS: The cLBP group exhibited greater thickness changes on the non-dominant side PM during contralateral hip flexion but not ipsilateral hip flexion (p= 0.369) compared to their healthy counterparts (p= 0.011; cLBP: resting 27.85 mm, activated 34.63 mm; healthy: resting 29.51 mm, activated 29.00 mm). There were no significant differences in dominant side PM thickness changes between the two groups during either contralateral or ipsilateral hip flexion (p= 0.306 and p= 0.077). CONCLUSION: Our findings suggest a potential overactivation of the PM in the cLBP population. This insight may aid in the development of tailored rehabilitation programs.

Persistence of vitamin D deficiency among Italian patients with acute myocardial infarction.

BACKGROUND AND AIMS: Vitamin D deficiency is a common cardiovascular risk factor associated with the development of atherosclerosis. We evaluated changes in 25(OH)D concentrations in 1510 patients with acute myocardial infarction (AMI) over a long observation period, including the COVID-19 pandemic. METHODS AND RESULTS: Patients were separated into four groups according to the year of enrolment, group 1 (2009-2010), group 2 (2014-2016), group 3 (2017-2019), and group 4 (2020-2022). The median 25(OH)D concentration in the overall cohort was 17.15 (10.3-24.7) ng/mL. The median plasma concentrations of 25(OH)D for groups 1, 2, 3, and 4 were 14.45 (7.73-22.58) ng/mL, 17.3 ng/mL (10.33-24.2), 18.95 (11.6-26.73) ng/mL and 19.05 (12.5-27.3) ng/mL, respectively. Although 25(OH)D levels increased over the years, the prevalence of vitamin D deficiency remained high in each group (68.4%, 61.4%, 53.8%, and 52% respectively). Hypovitaminosis D was predicted by the season influence (OR:2.03, p < 0.0001), higher body mass index (OR:1.25; p = 0.001), diabetes mellitus (OR:1.54; p = 0.001), smoking (OR:1.47; p = 0.001), older age (OR:1.07; p = 0.008), higher triglycerides levels (OR:1.02; p = 0.01), and female gender (OR:1.3; p = 0.038). After multivariable adjustment, vitamin D ≤ 20 ng/mL was an independent predictor of mortality. CONCLUSION: Vitamin D deficiency is highly prevalent and persistent in patients with AMI despite a trend towards increasing 25(OH)D concentrations over the years. The frequent lockdowns did not reduce the levels of 25(OH)D in the fourth group. Low levels of 25(OH)D are an independent predictor of mortality.

[Effect of Staphylococcal Nuclease and Tudor Domain Containing 1/SLC7A11 on the Occurrence and Development of Osteosarcoma by Inhibiting Ferroptosis].

Objective To investigate the effect of staphylococcal nuclease and tudor domain containing 1(SND1) on the biological function of osteosarcoma cells and decipher the mechanism of SND1 in regulating ferroptosis in osteosarcoma cells via SLC7A11. Methods Human osteoblasts hFOB1.19 and osteosarcoma cell lines Saos-2,U2OS,HOS,and 143B were cultured,in which the expression level of SND1 was determined.Small interfering RNA was employed to knock down the expression of SND1(si-SND1) in the osteosarcoma cell line HOS and 143B.The CCK8 assay kit,colony formation assay,and Transwell assay were employed to examine the effect of SND1 expression on the biological function of osteosarcoma cells.Furthermore,we altered the expression of SND1 and SLC7A11 in osteosarcoma cells to investigate the effect of SND1 on osteosarcoma ferroptosis via SLC7A11. Results The mRNA and protein levels of SND1 in Saos-2,U2OS,HOS,and 143B cells were higher than those in hFOB1.19 cells(all P<0.01).Compared with the control group,transfection with si-SND1 down-regulated the expression level of SND1 in HOS and 143B cells(all P<0.01),decreased the viability of HOS and 143B cells,reduced the number of colony formation,and inhibited cell invasion and migration(all P<0.001).The ferroptosis inducer Erastin promoted the apoptosis of HOS and 143B cells,while the ferroptosis inhibitor Ferrostatin-1 improved the viability of HOS and 143B cells(all P<0.001).After SND-1 knockdown,Erastin reduced the viability of HOS and 143B cells,while Ferrostatin-1 restored the cell viability(all P<0.001).After treatment with Erastin in the si-SND1 group,the levels of iron and malondialdehyde were elevated,and the level of glutathione was lowered(all P<0.001).The results of in vivo experiments showed that SND1 knockdown inhibited the mass of the transplanted tumor in 143B tumor-bearing nude mice(P<0.001).Knocking down the expression of SND1 resulted in down-regulated SLC7A11 expression(all P<0.001) and increased ferroptosis in HOS and 143B cells(P<0.001,P=0.020). Conclusions SND1 presents up-regulated expression in osteosarcoma cells.It may inhibit ferroptosis by up-regulating the expression of SLC7A11,thereby improving the viability of osteosarcoma cells.

Small nucleolar RNA and its potential role in the oncogenesis and development of colorectal cancer.

Small nucleolar RNAs (snoRNAs) represent a class of non-coding RNAs that play pivotal roles in post-transcriptional RNA processing and modification, thereby contributing significantly to the maintenance of cellular functions related to protein synthesis. SnoRNAs have been discovered to possess the ability to influence cell fate and alter disease progression, holding immense potential in controlling human diseases. It is suggested that the dysregulation of snoRNAs in cancer exhibits differential expression across various cancer types, stages, metastasis, treatment response and/or prognosis in patients. On the other hand, colorectal cancer (CRC), a prevalent malignancy of the digestive system, is characterized by high incidence and mortality rates, ranking as the third most common cancer type. Recent research indicates that snoRNA dysregulation is associated with CRC, as snoRNA expression significantly differs between normal and cancerous conditions. Consequently, assessing snoRNA expression level and function holds promise for the prognosis and diagnosis of CRC. Nevertheless, current comprehension of the potential roles of snoRNAs in CRC remains limited. This review offers a comprehensive survey of the aberrant regulation of snoRNAs in CRC, providing valuable insights into the discovery of novel biomarkers, therapeutic targets, and potential tools for the diagnosis and treatment of CRC and furnishing critical cues for advancing research into CRC and the judicious selection of therapeutic targets.

The crystal orientation of THF clathrates in nano-confinement by in situ polarized Raman spectroscopy.

Gas hydrates form at high pressure and low temperatures in marine sediments and permafrost regions of the earth. Despite forming in nanoporous structures, gas hydrates have been extensively studied only in bulk. Understanding nucleation and growth of gas hydrates in nonporous confinement can help create ways for storage and utilization as a future energy source. Herein, we introduce a new method for studying crystal orientation/tilt during tetrahydrofuran (THF) hydrate crystallization under the influence of nano-confinement using polarized Raman spectroscopy. Uniform cylindrical nanometer size pores of anodic aluminum oxide (AAO) are used as a model nano-confinement, and hydrate experiments are performed in a glass microsystem for control of the flash hydrate nucleation kinetics and analysis via in situ polarized Raman spectroscopy. The average THF hydrate crystal tilt of 56 ± 1° and 30.5 ± 0.5° were observed for the 20 nm and 40 nm diameter pores, respectively. Crystal tilt observed in 20 and 40-nanometer-size pores was proportional to the pore diameter, resulting in lower tilt relative to the axis of the confinement at larger diameter pores. The results indicate that the hydrates nucleation and growth mechanism can depend on the nanoconfinement size. A 1.6 ± 0.01 °C to 1.8 ± 0.01 °C depression in melting point compared to the bulk is predicted using the Gibbs-Thomson equation as a direct effect of nucleation in confinement on the hydrate properties.

Detection of germline variants in pancreatic cancer by next-generation sequencing and correlation analysis of clinical factors / 复旦学报（医学版）

Objective To investigate the rate of germline variants in patients with pancreatic cancer and clinical characteristics related with germline variants.Methods A total of 271 patients diagnosed with pancreatic cancer were enrolled in this study.Germline variants of 21 tumor susceptibility genes were detected by next-generation sequencing,and the relationship between germline variants and clinical factors such as age of onset,family history and personal history was analyzed.Results The rate of germline P/LP variants was 6.3%in unselected pancreatic cancer patients,but was high as 17.1%in genetic high-risk group patients(those with a family or personal history of cancer,or early-onset).Genes with higher frequency of germline variants in pancreatic cancer patients were PALB2,BRCA2,and ATM.Conclusion The rate of germline variants in overall pancreatic cancer patients is not high,but it increases significantly in genetic high-risk group,proving the importance of clinical factors in the screening of hereditary pancreatic cancer.

The value of high-throughput sequencing data reanalysis in identifying ERBB2 amplification in colorectal cancer patients / 复旦学报（医学版）

Objective To evaluate the value of high-throughput sequencing(HTS)data reanalysis that does not include ERBB2 copy number variation(CNV)analysis,in identifying ERBB2 amplification in patients with colorectal cancer.Methods The HTS data of 252 cases of colorectal cancer diagnosed by pathological biopsy who received peripheral blood cfDNA HTS detection samples were retrospectively analyzed.According to the HTS data of ERBB2 non-amplified samples judged by immunohistochemistry(IHC)and/or fluorescence in situ hybridization(FISH),the number of chromosome 17(Chr17)reads in the total number of reads was calculated the range of the ratio was initially determined as the threshold for prompting ERBB2 amplification.Suspected positive samples were screened according to thresholds and verified by digital PCR,IHC and FISH.Results The proportion of the number of Chr17 reads accounts for the number of total reads in the 89 cases of ERBB2 non-amplified samples determined by IHC and/or FISH ranged from 0.188 to 0.299(0.239±0.192).Using 0.298(1.25 times the mean)as the threshold indicating ERBB2 amplification,the data of 163 samples were analyzed,of which 7 cases were suspected to be positive,and the ratio ranged from 0.302 to 0.853.Among them,5 cases were determined to be positive by IHC and/or FISH,and 6 cases were confirmed to be positive by digital PCR.The ratio of the number of Chr17 reads to the number of total reads was positively correlated with the ratio of ERBB2/EIF2C1,and the correlation was good(r2=0.909).Conclusion The high-throughput sequencing data that does not cover the ERBB2 CNV analysis has a certain hint value for ERBB2 amplification in patients with colorectal cancer.

Synthesis of MnOOH and its application in a supporting hexagonal Pd/C catalyst for the oxygen reduction reaction.

With the expansion of global energy problems and the deepening of research on oxygen reduction reaction (ORR) in alkaline media, the development of low cost and high electrocatalytic performance catalysts has become a research hotspot. In this study, a hexagonal Pd-C-MnOOH composite catalyst was prepared by using the triblock copolymer P123 as the reducing agent and protective agent, sucrose as the carbon source and self-made MnOOH as the carrier under hydrothermal conditions. When the Pd load is 20% and the C/MnOOH ratio is 1 : 1, the 20% Pd-C-MnOOH-1 : 1 catalyst obtained by the one-step method has the highest ORR activity and stability in the alkaline system. At 1600 rpm, the limiting diffusion current density and half-wave potential of the 20% Pd-C-MnOOH-1 : 1 electrocatalyst are -4.78 mA cm-2 and 0.84 V, respectively, which are better than those of the commercial 20%Pd/C catalyst. According to the Koutecky-Levich (K-L) equation and the linear fitting results, the electron transfer number of the 20%Pd-C-MnOOH-1 : 1 electrocatalyst for the oxygen reduction reaction is 3.8, which is similar to that of a 4-electron process. After 1000 cycles, the limiting diffusion current density of the 20%Pd-C-MnOOH-1 : 1 catalyst is -4.61 mA cm-2, which only decreases by 3.7%, indicating that the 20%Pd-C-MnOOH-1 : 1 catalyst has good stability. The reason for the improvement of the ORR performance of the Pd-C-MnOOH composite catalyst is the improvement of the conductivity of the carbon layer formed by original carbonization, the regular hexagonal highly active Pd particles and the synergistic catalytic effect between Pd and MnOOH. The method of introducing triblock copolymers in the synthesis of oxides and metal-oxide composite catalysts is expected to be extended to other electrocatalysis fields.

Acupuncture Combined with Voice Training Improved Voice Function in Patients with Primary Muscular Tension Dysphonia (MTD): A Randomized, Three-Armed, Open-Label Clinical Trial.

Objective: This randomized controlled trial aimed to evaluate the clinical efficacy of acupuncture combined with voice training for treating patients with primary muscular tension dysphonia (MTD) (Qi stagnation and blood stasis type in traditional Chinese medicine). Methods: A total of 108 patients with primary MTD (Qi stagnation and blood stasis type) were recruited in this study. The participants were randomly divided into 3 equal groups: a test group and two control groups (control groups 1 and 2). An additional 38 participants without primary MTD were recruited as the healthy group. Control group 1 received acupuncture sessions 3 times per week on alternate days on the Hegu (LI 4), Taichong (LR 3), Open Voice No. 1 point, and Open Voice No. 2 points. Control group 2 received a 40-minute voice training session once weekly. The test group received both treatments. The total treatment course for all groups was 30 days. The healthy participants did not receive any interventions. The physiological and functional voice improvements after treatment were compared between all 3 MTD groups and healthy participants. The Voice Handicap Index (VHI-10), the VHI-10 emotional score, the Chinese Medicine Symptom Score Scale (TCM), and the Grade Roughness Breathiness Asthenia Strain (GRBAS) were used to evaluate the changes in the voice after treatment. A laryngeal muscle blood oxygen monitoring was used to measure the blood oxygen saturation (SO2) of the suprahyoid and infrahyoid muscles, and a stroboscopic laryngoscopy was used to measure the dysphonia severity index (DSI). Acoustic voice analysis was used to measure the maximum phonation time (MPT), the jitter, and the shimmer. Result: The SO2 levels of the laryngeal muscle were significantly higher in the healthy subjects than in pretreatment MTD patients and were correlated with the VHI-10 and DSI scores. A significant improvement in the physiological and functional scores, the total VHI-10, the GRBAS score, the voice acoustic analysis indices, MPT, jitter, shimmer, and DSI, was noted after treatment in all 3 MTD groups (P < 0.05). However, the posttreatment scores in the test group were significantly higher compared to control group 2, whose score were superior than that in control group 1 (P < 0.05). Both the test group and control group 1 showed a significant increase in the SO2 levels of the laryngeal muscles after treatment, where the test group had a higher elevation than control group 1. No significant difference was noted in the posttreatment SO2 of the laryngeal muscles in control group 2 (P > 0.05). Conclusion: Acupuncture monotherapy or in combination with voice training can reduce the anxiety emotion, relieve MTD-associated systemic symptoms, and increase the SO2 levels of the laryngeal muscle. This combination is a promising approach for the treatment of MTD. This trial is registered with ChiCTR2200061469.

Proximity hybridization induced bipedal DNA walker for label-free electrochemical detection of apolipoprotein A4 based on DNA meditated Ag nanoparticles growth.

Apolipoprotein A4 (Apo-A4) is considered as a prospective molecular biomarker for diagnosis of depression due to its neurosynaptic toxicity. Here, we propose a neighboring hybridization induced catalyzed hairpin assembly (CHA) driven bipedal DNA walker that mediates hybridization of Ag nanoparticles (Ag NPs) with DNA probes for highly sensitive electrochemical quantitative detection of Apo-A4. Driven by CHA, this bipedal DNA walker can spread all over the surface of the sensor, induce the HP1-HP2 double chain structure, make the surface of the sensor negatively charged, and adsorb a large number of Ag ions. After chemical reduction with hydroquinone, the Ag NPs formed provide signal tracers for electrochemical dissolution analysis of the target. The Ag NPs formed by chemical reduction of hydroquinone can provide signal traces for electrochemical stripping analysis of target thrombin. The linear range of this method is from 10 pg mL-1 to 1000 ng mL-1, and the detection limit is 5.1 pg mL-1. This enzyme-free and labeling detection method provides a new strategy for rapid clinical detection of Apo-A4 and accurate identification of depression.

Follicle-stimulating hormone is negatively associated with nonalcoholic fatty liver disease in a Chinese elderly population: a retrospective observational study.

BACKGROUND: Several studies have explored the connection between follicle-stimulating hormone (FSH) and nonalcoholic fatty liver disease (NAFLD). However, the impact of FSH elevation on NAFLD remains a topic of debate. Hence, this investigation aimed to evaluate the potential correlation between FSH levels and NAFLD in the aging population. METHODS: This was a retrospective observational cross-sectional study between July 2017 and August 2018 in our hospital. We used data obtained from 455 patients over 60 years old. Anthropometrics and laboratory tests were performed for each patient. NAFLD was diagnosed by sonographic features and the fatty liver index (LFI). RESULTS: Of the 455 patients, 200 (43.96%) had NAFLD on their ultrasound and 169 (37.14%) had NAFLD according to the LFI. An intraclass correlation coefficient of the two methods was 80.4% (P < 0.001). People with NAFLD on their ultrasound showed lower FSH levels (52.68 vs. 61.39 IU/L) and more unfavorable metabolic profiles. FSH was negatively correlated with age, alanine aminotransferase, estradiol, testosterone, systolic blood pressure, waist, body mass index, fasting blood glucose, postload plasma glucose and positive associated with total cholesterol, high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol by Spearman correlation analysis (all P < 0.05). By controlling for all confounding factors, the odds ratios (OR) of FSH for NAFLD were determined in elderly individuals, both men and women, aged 60-70 years and over 70 years. These ORs were found to be 0.937, 0.982, 0.983, and 0.973, respectively, with corresponding 95% confidence intervals (CI) of 0.892-0.984 (P = 0.009), 0.971-0.993 (P = 0.002), 0.967-0.999 (P = 0.033), and 0.958-0.989 (P = 0.001). In addition, our findings demonstrated no significant correlation between FSH and advanced fibrosis when adjusting for potential covariates. The OR for advanced fibrosis was 0.979 (95% CI, 0.938-1.022, P = 0.339). Additionally, ROC curve analysis showed an optimal cut-off value of 66.91 for women and 15.25 for men for NAFLD diagnosis. CONCLUSIONS: There was an inverse relationship observed between levels of FSH in the blood serum and NAFLD in the elderly population. These findings suggest that reduced FSH levels might serve as a potential risk factor or biomarker for NAFLD in the elderly.

Dose dependent effect of nitrogen on the phyto extractability of Cd in metal contaminated soil using Wedelia trilobata.

Cadmium (Cd) is one of the toxic heavy metal that negatively affect plant growth and compromise food safety for human consumption. Nitrogen (N) is an essential macronutrient for plant growth and development. It may enhance Cd tolerance of invasive plant species by maintaining biochemical and physiological characteristics during phytoextraction of Cd. A comparative study was conducted to evaluate the phenotypical and physiological responses of invasive W. trilobata and native W. chinensis under low Cd (10 µM) and high Cd (80 µM) stress, along with different N levels (i.e., normal 91.05 mg kg-1 and low 0.9105 mg kg-1). Under low-N and Cd stress, the growth of leaves, stem and roots in W. trilobata was significantly increased by 35-23%, 25-28%, and 35-35%, respectively, compared to W. chinensis. Wedelia trilobata exhibited heightened antioxidant activities of catalase and peroxidase were significantly increased under Cd stress to alleviate oxidative stress. Similarly, flavonoid content was significantly increased by 40-50% in W. trilobata to promote Cd tolerance via activation of the secondary metabolites. An adverse effect of Cd in the leaves of W. chinensis was further verified by a novel hyperspectral imaging technology in the form of normalized differential vegetation index (NDVI) and photochemical reflectance index (PRI) compared to W. trilobata. Additionally, W. trilobata increased the Cd tolerance by regulating Cd accumulation in the shoots and roots, bolstering its potential for phytoextraction potential. This study demonstrated that W. trilobata positively responds to Cd with enhanced growth and antioxidant capabilities, providing a new platform for phytoremediation in agricultural lands to protect the environment from heavy metals pollution.