Synovial osteoclastogenesis mediated by chondrocyte-secreted TNFα promotes TMJ condylar resorption.

BACKGROUND: Insufficient occlusal support (IOS) frequently causes subchondral bone absorption in temporomandibular joint osteoarthritis, and the underlying mechanism requires further investigation. METHODS: An IOS model was established by abrading rat molars. Micro-computed tomography was used to evaluate subchondral bone changes. Osteoclastogenesis of synovium-derived macrophages (SDMs) was confirmed by TRAP staining. Cartilage-specific TNFα depletion was achieved by intra-articular injection of adeno-associated virus carrying shRNA against murine TNFα under control of collagen type II. In vitro, chondrocytes were mechanically compressed and conditioned medium (CM) was collected to detect its ability to induce osteoclastogenesis of SDMs. RESULTS: Synovial osteoclastogenesis and condyle resorption were observed following IOS. TNFα level was elevated in hypertrophic chondrocytes after IOS. Synovial Wnt5a level increased, but Wnt3a level decreased after IOS. Depletion of TNFα in chondrocytes alleviated the synovial osteoclastogenesis and condyle bone resorption. In vitro compression of chondrocytes potentiated TNFα expression and secretion. The CM promoted osteoclastogenesis of SDMs, which were partially prohibited by TNFα neutralizing antibody. Furthermore, inhibition of Wnt3a facilitated osteoclastogenesis, whereas inhibition of Wnt5a partially suppressed osteoclastogenesis, of SDMs cultured in CM. CONCLUSION: Chondrocyte-secreted TNFα induced by IOS is a critical regulator of synovial osteoclastogenesis and subsequent condylar resorption, partially through non-canonical Wnt5a pathway.

PepDRED: De Novo Peptide Design with Strong Binding Affinity for Target Protein.

De novo design of peptides that bind specifically to functional proteins is beneficial for diagnostics and therapeutics. However, complex permutations and combinations of amino acids pose significant challenges to the rational design of peptides with desirable stability and affinity. Herein, we develop a computational-based evolution method, namely, peptidomimetics-driven recognition elements design (PepDRED), to derive hemoglobin-inspired peptidomimetics. PepDRED mimics the natural evolutionism pipeline to generate stable apovariant (AVs) structures for wild-type counterparts via automated point mutations and validates their efficiency through free binding energy analysis and per residue energy decomposition analysis. For application demonstration, we applied PepDRED to design de novo peptides to bind FhuA, a typical TonB-dependent transporter (TBDT). TBDTs are Gram-negative bacterial outer membrane proteins responsible for iron transport and vital for bacterial resistance. PepDRED generated a pool of AVs and proceeded to reach an optimized peptide, AV440, with a remarkable binding affinity of -21 kcal/mol. AV440 is ∼2.5-fold stronger than the existing FhuA inhibitor Microcin J25. Network energy analysis further unveils that incorporating methionine (M42) in the N-terminal region significantly enhances inter-residue contacts and binding affinity. PepDRED offers a prompt and efficient in silico approach to develop potent peptide candidates for target proteins.

[Bletilla striata ecological planting patterns and technical principle analysis].

Bletilla striata is a shallow-rooted herbaceous plant, which is highly dependent on the planting environment.In order to improve the quality of B.striata effectively and solve the contradiction between the production of traditional Chinese medicine and the ecological environment, a variety of simulated cultivation patterns have been explored in various producing areas. Through field investigation and literature collation, this paper sorted out 24 sets of simulated cultivation modes of B.striata, including 4 kinds of sub-forest imitative wild planting techniques, 10 kinds of B.striata-economic forest cooperative development mode, 14 kinds of intercropping techniques of B.striata and 1 kind of ecological rotation technique of B.striata-edible fungi under economic forest. Combining economic benefit, social benefit and ecological benefit, the advantages and disadvantages of these planting patterns were compared. The ecological principles of B.striata simulative cultivation are analyzed in detail, as follows:(1) the wild cultivation of B.striata simulative cultivation under forest is to utilize the complementary principle of land resources under forest and spatial light and heat resources, and carry out the compound cultivation of cultivating forest with medicine and growing with short growth;(2) the intercropping of B.striata makes full use of the difference in height and height of the two plants to meet their needs for light, humidity and ventilation, reduce the cost of shading and weeding, improve the risk-resistant ability of Chinese medicinal materials cultivation, and increase the utilization rate of land, and give consideration to the benefits of both length and length;(3) the ecological rotation technology of "B.striata-edible fungi" in economic forests is to realize the effective utilization of waste bacteria and residues according to the mutually beneficial relationship between B.striata and edible fungi. The promotion and optimization of B.striata imitated wild cultivation technology will further promote the sustainable development of B.striata industry.

4-phenylbutyric acid attenuates endoplasmic reticulum stress-mediated apoptosis and protects the hepatocytes from intermittent hypoxia-induced injury.

PURPOSE: To investigate the effect of 4-phenylbutyric acid (4-PBA) on intermittent hypoxia (IH)-induced liver cell injury and to clarify the underlying mechanisms. METHODS: L02 cells (normal human liver cells) were cultured in normoxic condition or subjected to intermittent hypoxia for 4, 8, and 12 h. A part of hypoxia-treated L02 cells was applied with 4-PBA 1 h before exposure to hypoxia. The effect of 4-PBA on liver injury, hepatocyte apoptosis, endoplasmic reticulum stress (ERS), and PERK-eIFa2-ATF4-CHOP apoptotic pathway was investigated. RESULTS: (1) IH caused apoptosis in hepatocyte; (2) IH caused ERS in hepatocyte; (3) IH caused hepatic injury; (4) 4-PBA attenuated IH-induced liver cell injury; (5) 4-PBA protected liver cell from IH-induced apoptosis; (6) 4-PBA suppressed ERS-related apoptotic pathway (PERK-eIFa2-ATF4-CHOP), but did not suppress IH-induced unfold protein reaction (UPR). CONCLUSIONS: 4-PBA could protect liver cells by suppressing IH-induced apoptosis mediated by ERS, but not by reducing the UPR.

Highly sensitive wearable strain sensor based on silver nanowires and nanoparticles.

Here, we propose a highly sensitive and stretchable strain sensor based on silver nanoparticles and nanowires (Ag NPs and NWs), advancing the rapid development of electronic skin. To improve the sensitivity of strain sensors based on silver nanowires (Ag NWs), Ag NPs and NWs were added to polydimethylsiloxane (PDMS) as an aid filler. Silver nanoparticles (Ag NPs) increase the conductive paths for electrons, leading to the low resistance of the resulting sensor (14.9 Ω). The strain sensor based on Ag NPs and NWs showed strong piezoresistivity with a tunable gauge factor (GF) at 3766, and a change in resistance as the strain linearly increased from 0% to 28.1%. The high GF demonstrates the irreplaceable role of Ag NPs in the sensor. Moreover, the applicability of our high-performance strain sensor has been demonstrated by its ability to sense movements caused by human talking, finger bending, wrist raising and walking.

Exploring the Molecular Mechanism and Biomarker of Recurrent Aphthous Stomatitis Based on Gene Expression Microarray.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is one of the most common chronic oral diseases with morbidity ranging from 5% to 20%. The pathogenesis is still not fully understood though immune dysregulation and local trauma have been implicated and the curative effect that can be achieved through current therapy is mainly to alleviate the pain. So, the understanding of its molecular mechanisms can allow the prevention and treatment of RAS at the molecular level. METHODS: 14 normal tissues and 14 ulcerated tissues were subjected to Affymetrix Human Genome U133 Plus 2.0 Array transcriptome analysis. Then, Gene Set Expression Analysis and Gene Pattern tools were carried out to determine the gene expression differences between normal and ulcerated tissues. qRT-PCR was used to validate the expression level of identified genes in 10 normal and 10 ulcerated tissues. RESULTS: We obtained a total of 1379 DEGs with adjPval < 0.05 and |logFC| > 1 including 1052 up-regulated genes and 327 down-regulated genes. 4 GO terms and 4 KEGG pathways were screened out by comparing the genomewide gene set expression patterns of normal and ulcerated tissues. 7 genes involved in RAS were identified from the VEGF signaling pathway. CONCLUSIONS: Present findings demonstrated that several immune processes have a deep impact on RAS and a number of genes involved in the VEGF signaling pathway may be critical mediators or participators in the pathogenesis of RAS.

Consequences, measurement, and evaluation of the costs associated with adverse drug reactions among hospitalized patients in China.

BACKGROUND: Adverse drug reactions (ADRs) are a leading cause of morbidity in developed countries and represent a substantial burden on health-care resources. Many countries spent 15% to 20% of their hospital budgets to treat drug complications. However, few studies have measured the pharmacoeconomic effects of ADRs on hospitalized patients in China. The study estimates the costs of ADRs as identified from the spontaneous voluntary reports completed from healthcare professionals. To do so, we calculate these costs, determine the sum of Medicare payments and their proportion of total healthcare spending, and evaluate the incidence of ADRs, characteristics of hospitalized ADR patients, and outcomes of ADRs in China. METHODS: This retrospective survey studied patients who experienced ADRs during their hospitalization at a Chinese tertiary-care teaching hospital. The patients were divided into group A and group B according to general ADRs and serious ADRs in Provisions for Adverse Drug Reaction Monitoring and Reporting. The direct costs included treatment fees, inspection fees, laboratory fees, materials fees, bed charges, drug charges, nursing care, meals, and other expenses and the sunk-cost losses were calculated according to the hospital information system (HIS). Indirect costs of ADR treatment were calculated according to the human capital approach. The epidemiological characteristics of ADRs were evaluated. RESULTS: 2739 were diagnosed with ADR during the study period, which translates to an ADR rate of 0.81%. The total socioeconomic loss from 2739 cases of ADR was estimated at ¥817401.69, consisting of direct costs of ¥603252.81 and indirect costs of ¥214148.88. On average, the costs per patient amounted to ¥196.10 in group A, ¥7032.29 in group B. The sum of medicare payment and proportion were ¥219061.13 (65.23%) and ¥105422.02 (39.42%) in group A and B. The ADR incidence in old-age patients was significantly higher than in other age groups (P < 0.0001). The most common drug class associated with ADRs represented antibiotics (957 patients, 34.94%). CONCLUSIONS: The costs of especially severe ADRs could not be ignored, and in this hospital 0.13% of patients were diagnosed with ADRs associated with relatively higher direct costs than who suffered from mild ADRs, largely due to extended hospitalization.

Modified Nuss procedure is a safe choice for recurrent pectus excavatum after previous open repair experience of 26 cases.

PURPOSE: This study is aiming to investigate the feasibility and effect of applying modified Nuss procedure on recurrent pectus excavatum following previous open repair. METHODS: By retrospectively reviewing patients of pectus excavatum enrolled in our department from July 2007 to August 2012, we find 27 cases of recurrent PE who received open repair previously. Twenty-six patients received Nuss repair, while one patient refused. Relevant data are collected and processed. A 3-month follow-up after operation is also reviewed. Analysis of data is conducted. RESULTS: Twenty-six recurrent patients underwent modified Nuss procedure safely. Pneumothorax after operation occurred in one case. Pleural effusion occurred for every case, most were mild in quantity except two cases whose pleural effusion were moderate. All patients left hospital within 2 weeks after operation except one patient who died of respiration failure. Mean postoperative Haller Index is significantly different from the preoperative one. Cosmetic effect was excellent for 5 cases, good for 15 cases, moderate for 6 cases. In a 3-month follow-up, no bar displacement or rejection happened and pleural effusion was completely absorbed. CONCLUSION: Although technically challenging, Nuss procedure is feasible and good for recurrent PE after open repair.

Application of orthodontics combined with porcelain laminate veneers in the aesthetic restoration and flora regulation of anterior teeth.

To evaluate the effectiveness of orthodontics in combination with porcelain laminate veneers (PLV) in the aesthetic restoration and flora regulation of anterior teeth. A retrospective analysis of 336 patients who underwent aesthetic restoration of anterior teeth in our hospital from April 2019 to September 2022 was performed and divided into a control group (n = 168) and an observation group (n = 168) according to the restorative modality. The restorative modality in the control group was conventional restorative remediation, while the restorative modality in the observation group was orthodontic combined with PLV treatment. To evaluate the excellent rate of aesthetic restoration of anterior teeth in the 2 groups, and compare the color, shape, degree of translucency, edge aesthetic score, complications and satisfaction rate of restoration of anterior teeth in the 2 groups before and after restoration. The observation group had a significantly higher rate of excellent aesthetic restorations (95.23%) compared to the control group (80.95%) (P < .001). The scores of anterior tooth color, morphology, degree of translucency and marginal aesthetics were improved in both groups after restoration compared to before restoration, and the scores were significantly higher in the observation group (P < .05). After restoration, the subgingival Digestive streptococcus, Campylobacter and Propionibacterium increased in both groups, but the number of bacterial strains was significantly less in the observation group (P < .05). Compared with the total complication rate in the control group (16.66%), the total complication rate in the observation group (2.38%) was significantly lower (P < .001). Compared with the control group (85.71%), the observation group had a significantly higher restoration satisfaction rate of 97.61%, with a statistically significant difference (P < .001). The application of orthodontics combined with PLV in the aesthetic restoration of anterior teeth has a significant clinical effect, which is conducive to improving the aesthetic restoration and satisfaction rate of anterior teeth, reducing the subgingival microbial imbalance and decreasing the incidence of complications.

WITHDRAWN: Analysis of the Efficacy of Drilling Decompression Autologous Bone Marrow and Allogeneic Bone Grafting in the Treatment of HIV-positive Patients with Early Osteonecrosis of the Femoral Head

The article has been withdrawn at the request of the author of the journal Current HIV Research (CHIVR).Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused. The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

Analysis of type I hypersensitivity-induced inflammatory response in children of different age groups with acute appendicitis.

OBJECTIVE: To explore the differences in type I hypersensitivity-induced inflammatory response among children of different age groups with acute appendicitis. METHODS: We selected children diagnosed with "acute appendicitis" who underwent surgery in the Department of General Surgery of Anhui Provincial Children's Hospital from January 2022 to June 2022 and collected their basic data. We divided them into two groups according to age: the infant group (less than 3 years old) and the pediatric group (3-14 years old). The gender, age, onset time, hospital stay, preoperative white blood cells, percentage of neutrophils, C-reactive protein (CRP), and enzyme-linked immunosorbent assay (ELISA) were collected to determine the levels of immunoglobulin E (IgE), interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-6 (IL-6), and interleukin-9 (IL-9) in appendicular lavage fluid, and the differences between the two groups were compared. RESULTS: There were 15 children in the infant group and 15 in the pediatric group. There was no significant difference between the two groups with respect to onset time and gender. The hospitalization time in the pediatric group was (5.7 ± 2.1) d, the preoperative white blood cells were (14.3 ± 3.7) × 10^9/mL, neutrophil percentage was (84.5 ± 6.3)%, and CRP was (20.0 ± 17.9) mg/mL. The hospitalization time of the infant group was (8.0 ± 3.1) d, the preoperative white blood cells were (19.0 ± 3.8) × 10^9/mL, neutrophil percentage was (77.8 ± 10.4)%, and CRP was (42.5 ± 25.0) mg/mL. The differences between the two groups were significant. There was no significant difference in IL-5 concentration between the two groups in the appendicular lavage fluid. IgE (610.74 ± 72.56) ng/mL, IL-4 (30.80 ± 12.04) ng/mL, IL-6 (118.09 ± 14.29) ng/mL, IL-9 (133.94 ± 16.00) ng/mL were found in the infant group, and IgE (495.61 ± 95.09) ng/mL, IL-4 (22.68 ± 7.05) ng/mL, IL-6 (98.22 ± 22.18) ng/mL and IL-9 (107.86 ± 27.34) ng/mL were found in the pediatric group, and the differences between the two groups were statistically significant. CONCLUSIONS: The inflammatory response in children with acute appendicitis was associated with type I hypersensitivity-induced inflammatory responses, and the type I hypersensitivity was more intense in children in the lower age group.

CT-Assisted Improvements in the Accuracy of the Intraoperative Frozen Section Examination of Ground-Glass Density Nodules.

OBJECTIVES: The intraoperative frozen section examination (IFSE) of pulmonary ground-glass density nodules (GGNs) is a great challenge. In the present study, through comparing the correlation between the computed tomography (CT) findings and pathological diagnosis of GGNs, the CT features as independent risk factors affecting the examination were defined, and their value in the rapid intraoperative examination of GGNs was explored. METHODS: The relevant clinical data of 90 patients with GGNs on CT were collected, and all CT findings of GGNs, including the maximum transverse diameter, average CT value, spiculation, solid component, vascular sign, air sign, bronchus sign, lobulation, and pleural indentation, were recorded. All the cases received thoracoscopic surgery, and final pathological results were obtained. The cases were divided into three groups on the basis of pathological diagnosis: benign/atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS)/microinvasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC). The CT findings were analyzed statistically, the independent risk factors were identified through the intergroup bivariate logistic regression analysis on variables with statistically significant differences, and a receiver operating curve (ROC) was plotted to establish a logistic regression model for diagnosing GGNs. A retrospective analysis was conducted on the coincidence rate of the rapid intraoperative and routine postoperative pathological examinations of the 90 cases with GGNs. The relevant clinical data of 49 cases with GGNs were collected. Conventional rapid intraoperative examination and CT-assisted rapid intraoperative examination were performed, and their coincidence rates with routine postoperative pathological examinations were compared. RESULTS: No statistical differences in the onset age, gender, smoking history, and family history of malignant tumors were found among cases with GGNs in the identification of benign/AAH, AIS/MIA, and IAC (P = 0.158, P = 0.947, P = 0.746, P = 0.566). No statistically significant difference was found among the three groups in terms of CT findings, such as lobulation, bronchus sign, pleural indentation, spiculation, vascular sign, and solid component (P > 0.05). The air sign, the maximum transverse diameter of GGNs, and average CT value showed statistically significant differences among the groups (P < 0.001, P < 0.05, P < 0.001). Bivariate logistic regression analysis was performed on three risk factors, and the predicted probability value was obtained. A ROC curve was plotted by using the maximum transverse diameter as a predictor for analysis between the groups with benign/AAH and AIS/MIA, and the results demonstrated that the area under the curve (AUC) was 0.692. A ROC curve was plotted by using the predicted probability value, maximum transverse diameter, and average CT value as predictors for distinguishing between the groups with AIS/MIA and IAC, and the results showed that the AUC values of the predicted probability value, maximum transverse diameter, and CT value were 0.920, 0.816, and 0.772, respectively. A regression model [Logit (P) = 2.304 - 2.689X1 + 0.302X2 + 0.011X3] was established to identify GGNs as IAC, obtaining AUC values of up to 0.920 for the groups with AIS/MIA and IAC, the sensitivity of 0.821, and the specificity of 0.894. The coincidence rate of rapid intraoperative and routine postoperative pathological examinations taken for modeling was 79.3%, that of conventional IFSE and postoperative pathological examination in prospective studies was 83.7%, and that of CT-assisted rapid intraoperative and postoperative pathological examinations was 98.0%. The former two were statistically different from the last one (P = 0.003 and P = 0.031, respectively). CONCLUSION: The air sign, maximum transverse diameter, and average CT value of the CT findings of GGNs had superior capabilities to enhance the pathologic classification of GGNs. The auxiliary function of the comprehensive multifactor analysis of GGNs was better than that of single-factor analysis. CT-assisted diagnosis can improve the accuracy of rapid intraoperative examination, thereby increasing the accuracy of the selection of operative approaches in clinical practice.

The Construction of Folk Sports Featured Towns Based on Intelligent Building Technology Based on the Internet of Things.

With the emergence of the Internet of Things, technology and Internet thinking have entered traditional communities, and combined with traditional technologies, many new and better management methods and solutions have been born. Among them, the concept of intelligent buildings is also known to people. Based on big data technology, cloud computing technology, and Internet of Things technology, smart buildings provide smart and convenient devices and services for smart device users. The Internet of Things technology is entering our lives at an unimaginable speed. It has been applied in many fields. Smart home, smart transportation, smart medical, smart agriculture, and smart grid are widely used in the Internet of Things technology. The application of Internet of Things technology to the construction of folk sports characteristic towns is of great significance. The construction of folk sports characteristic towns and the protection of intangible cultural heritage have the same purpose and interoperability of elements as the development of traditional cities. From the perspective of protecting folk culture and intangible cultural heritage, it is effective to promote the development of small towns with folk custom characteristics. Based on the research on the construction of folk-custom sports towns, this paper proposes a series of data model analysis and analyzes the proportion of sports preferences in the survey of volunteers in the folk-custom sports towns. The final result of the research shows that the ball games sports personnel accounted for the largest proportion, with 156 people accounting for 48.15%. This shows that about half of the people like ball sports, which proves that ball sports should be the mainstay of folk sports towns, and other sports should be supplemented by other sports.

Expression and Clinicopathological Significance of SOX11 in Small-Cell Lung Cancer.

Objective: This study aims to investigate the expression of neuronal transcription factor SOX11 in small-cell lung cancer (SCLC) and compare it with the expression of CD56 (nerve cell adhesion molecule), synaptophysin (Syn), chromogranin A (CgA), and thyroid transcription factor-1 (TTF-1) to explore the application value of SOX11 in the pathological diagnosis of SCLC. Methods: Immunohistochemical methods were used to detect the expression of SOX11, TTF-1, CD56, Syn, and CgA in 120 lung tumor tissues, and experimental results were analyzed using SPSS23.0 statistical software. Results: Immunohistochemical results showed that in the 120 lung tumor samples, SOX11 was highly expressed in SCLC and localized to the nucleus, with low or no expression in control carcinoid/lung neuroendocrine tumors, lung adenocarcinomas, and lung squamous cell carcinomas. Statistical analysis results revealed the following points. First, the expression of SOX11 was closely related to the tumor histological type. The expression of SOX11 in SCLC (positive rate of 63.33%) was significantly higher than that in carcinoid/neuroendocrine tumors (positive rate of 12.50%), lung adenocarcinoma (positive rate of 0%), and lung squamous cell carcinoma (positive rate of 0%). Second, immunohistochemical investigation of 60 SCLC cases revealed that the highest positive rates of CD56, TTF-1, and Syn, respectively, were 93.33 percent, 95 percent, and 86.67 percent. SOX11 also exhibited high sensitivity (0.633) and specificity (0.875) in SCLC. The positive rates of SOX11 and CgA were 63.33% and 50.00%, respectively. Statistical results revealed that the positive rate of CgA had no significant difference (P > 0.05). Lastly, the combined use of antibodies SOX11, CgA, CD56, Syn, and TTF-1 was more beneficial to improving the diagnosis rate of SCLC than the single use of one or two antibodies. Conclusion: The expression of SOX11 in different histological types of lung tumors differs considerably. SOX11 is highly expressed in SCLC. SOX11 can be used as a beneficial supplement to the combination of classical neuroendocrine markers and in combination with CgA, CD56, Syn, and TTF-1 to assist in the diagnosis of SCLC.

Case Report: Aumolertinib as Neoadjuvant Therapy for Patients With Unresectable Stage III Non-Small Cell Lung Cancer With Activated EGFR Mutation: Case Series.

Background: There is no standard treatment for stage III lung cancer due to its low surgical resection rate, and improving PFS and survival of patients with III NSCLC has become an urgent challenge in clinical treatment. For EGFR mutation-positive patients, targeted therapy has the remarkable feature of high efficiency and low toxicity compared with first-line standard chemotherapy, and targeted neoadjuvant therapy needs to be further explored. Method: We report 3 diagnosed cases of locally advanced unresectable NSCLC with EGFR-sensitive mutations who first received 1-2 cycles of preoperative chemotherapy neoadjuvant therapy and were treated with 110 mg daily of 3rd-generation EGFR-TKI aumolertinib instead because of poor efficacy or safety intolerance. Result: After 2 cycles of aumolertinib treatment, all 3 patients achieved symptomatic remission and significant tumor size reduction and achieved downstaging to allow surgical treatment. No additional operative difficulties were added during the surgery. They continued to receive adjuvant therapy with the original dose of aumolertinib after surgical treatment, and no evidence of tumor recurrence was found until the most recent imaging examination. In addition, the course of neoadjuvant and adjuvant therapy was free of serious adverse effects. Conclusion: Perioperative treatment of these three cases of locally advanced unresectable NSCLC with EGFR-sensitive mutations with the third-generation EGFR-TKI aumolertinib showed significant efficacy and excellent safety and may be a new option for targeted therapy in the perioperative period.

P3HT-based organic field effect transistor for low-cost, label-free detection of immunoglobulin G.

Currently, organic field effect transistors (OFETs) are widely used in the field of biodetection because of their inherent gain amplification function and good biocompatibility. However, the vast majority of OFET biosensors have disadvantages including a long preparation cycle, complicated processing and expensive materials. Thus, this paper proposes a simple and inexpensive preparation method for label-free detection of immunoglobulin G (IgG). In this work an active dielectric bilayer field effect transistor with 3D-printed silver source and drain electrodes was used. The active layer was modified by physically adsorbing an anti-IgG antibody on P3HT as a recognition element and then sealed with bovine serum albumin (BSA) to prevent nonspecific adsorption. The carrier mobility of the bilayer dielectric layer active field effect transistor reached 4.6 × 10-2 cm2/Vs, and the dynamic detection range for IgG spanned 6 orders of magnitude with a detection limit of 2.9 Picomolar (pM). Controlled experiments demonstrated that the developed sensor has high selectivity for IgG. Overall, this easy-to-operate and low-cost OFET biosensor has broad commercialization prospects and lays the foundation for the early clinical detection of disease-causing biomolecules.

The effectiveness of artificial intelligence-based automated grading and training system in education of manual detection of diabetic retinopathy.

Background: The purpose of this study is to develop an artificial intelligence (AI)-based automated diabetic retinopathy (DR) grading and training system from a real-world diabetic dataset of China, and in particular, to investigate its effectiveness as a learning tool of DR manual grading for medical students. Methods: We developed an automated DR grading and training system equipped with an AI-driven diagnosis algorithm to highlight highly prognostic related regions in the input image. Less experienced prospective physicians received pre- and post-training tests by the AI diagnosis platform. Then, changes in the diagnostic accuracy of the participants were evaluated. Results: We randomly selected 8,063 cases diagnosed with DR and 7,925 with non-DR fundus images from type 2 diabetes patients. The automated DR grading system we developed achieved accuracy, sensitivity/specificity, and AUC values of 0.965, 0.965/0.966, and 0.980 for moderate or worse DR (95 percent CI: 0.976-0.984). When the graders received assistance from the output of the AI system, the metrics were enhanced in varying degrees. The automated DR grading system helped to improve the accuracy of human graders, i.e., junior residents and medical students, from 0.947 and 0.915 to 0.978 and 0.954, respectively. Conclusion: The AI-based systemdemonstrated high diagnostic accuracy for the detection of DR on fundus images from real-world diabetics, and could be utilized as a training aid system for trainees lacking formal instruction on DR management.

Effect of foliage applied chitosan-based silicon nanoparticles on arsenic uptake and translocation in rice (Oryza sativa L.).

In this study, chitosan-based silicon nanoparticles (Chsi-NPs) are prepared that primarily consists of C (57.9%), O (31.3%), N (5.6%), and Si (3.5%) and are 10-180 nm in size. We then explore the effect on the foliage applied on rice planted on soil contaminated with 104 mg·kg-1 arsenic (As); low (3 mg·L-1)and high (15 mg·L-1) doses of the foliar Chsi-NPs are administered during the rice grain filling stage. The results showed that the higher dose foliar Chsi-NPs treatment reduced the As concentration in the grain by 61.2% but increased As concentration in the leaves by 47.1% compared to the control treatment. The foliar spraying of the Chsi-NPs inhibited As transport to the grain by facilitating the attachment of As to the cell wall, with higher doses of the foliar Chsi-NPs treatment increased by 8.7%. The foliar spraying of Chsi-NPs increased the malondialdehyde levels by 18.4%, the catalase activity by 49.0%, and the glutathione activity by 99.0%. These results indicated that the foliar Chsi-NPs application was effective for alleviating As toxicity and accumulation in rice. This study provides a novel method for effectively alleviating As accumulation in rice.

SUV39H2/KMT1B Inhibits the cardiomyocyte senescence phenotype by down-regulating BTG2/PC3.

Suppressor of variegation 3-9 homolog 2 (SUV39H2/KMT1B), a member of the SUV39 subfamily of lysine methyltransferases (KMTs), functions as an oncogene in various types of cancers. Here, we demonstrate a novel function of SUV39H2 that drives the cardiomyocyte aging process through BTG2. In our study, cardiomyocyte aging was induced by H2O2 and aging cells exhibited increases in SUV39H2. Knockdown of SUV39H2 accelerated cardiomyocyte senescence, while overexpression of SUV39H2 inhibited the cardiomyocyte senescence phenotype. These effects of SUV39H2 on cardiomyocytes were independent of DNA damage and mitochondrial dysfunction. Interestingly, RNA sequencing and bioinformatics analyses identified a strong correlation between SUV39H2 and BTG2. In addition to this, BTG2 protein levels were significantly increased in SUV39H2-deficient cardiomyocytes, and BTG2 knockdown virtually rescued the cardiomyocyte senescence phenotype induced by SUV39H2 knockdown. Taken together, these results indicate that SUV39H2 protects cardiomyocytes from H2O2 exposure-induced oxidative stress, DNA damage, and mitochondrial dysfunction by regulating the p53-BTG2 pathway. Our findings provide evidence that the activation of SUV39H2 has therapeutic or preventive potential against cardiac aging.