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1.
J Biomed Opt ; 30(Suppl 1): S13702, 2025 Jan.
Article in English | MEDLINE | ID: mdl-39034960

ABSTRACT

Significance: Near-infrared autofluorescence (NIRAF) utilizes the natural autofluorescence of parathyroid glands (PGs) to improve their identification during thyroid surgeries, reducing the risk of inadvertent removal and subsequent complications such as hypoparathyroidism. This study evaluates NIRAF's effectiveness in real-world surgical settings, highlighting its potential to enhance surgical outcomes and patient safety. Aim: We evaluate the effectiveness of NIRAF in detecting PGs during thyroidectomy and central neck dissection and investigate autofluorescence characteristics in both fresh and paraffin-embedded tissues. Approach: We included 101 patients diagnosed with papillary thyroid cancer who underwent surgeries in 2022 and 2023. We assessed NIRAF's ability to locate PGs, confirmed via parathyroid hormone assays, and involved both junior and senior surgeons. We measured the accuracy, speed, and agreement levels of each method and analyzed autofluorescence persistence and variation over 10 years, alongside the expression of calcium-sensing receptor (CaSR) and vitamin D. Results: NIRAF demonstrated a sensitivity of 89.5% and a negative predictive value of 89.1%. However, its specificity and positive predictive value (PPV) were 61.2% and 62.3%, respectively, which are considered lower. The kappa statistic indicated moderate to substantial agreement (kappa = 0.478; P < 0.001 ). Senior surgeons achieved high specificity (86.2%) and PPV (85.3%), with substantial agreement (kappa = 0.847; P < 0.001 ). In contrast, junior surgeons displayed the lowest kappa statistic among the groups, indicating minimal agreement (kappa = 0.381; P < 0.001 ). Common errors in NIRAF included interference from brown fat and eschar. In addition, paraffin-embedded samples retained stable autofluorescence over 10 years, showing no significant correlation with CaSR and vitamin D levels. Conclusions: NIRAF is useful for PG identification in thyroid and neck surgeries, enhancing efficiency and reducing inadvertent PG removals. The stability of autofluorescence in paraffin samples suggests its long-term viability, with false positives providing insights for further improvements in NIRAF technology.


Subject(s)
Optical Imaging , Parathyroid Glands , Spectroscopy, Near-Infrared , Thyroidectomy , Humans , Parathyroid Glands/surgery , Parathyroid Glands/metabolism , Male , Female , Middle Aged , Optical Imaging/methods , Adult , Spectroscopy, Near-Infrared/methods , Paraffin Embedding/methods , Aged , Thyroid Cancer, Papillary/surgery , Thyroid Cancer, Papillary/pathology , Thyroid Cancer, Papillary/metabolism , Receptors, Calcium-Sensing/metabolism , Receptors, Calcium-Sensing/analysis
2.
Nature ; 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39236747

ABSTRACT

Two-terminal monolithic perovskite-silicon tandem solar cells demonstrate huge advantages in power conversion efficiency (PCE) compared to their respective single-junction counterparts1,2. However, suppressing interfacial recombination at the wide-bandgap perovskite/electron transport layer interface, without compromising its superior charge transport performance, remains a significant challenge for perovskite-silicon tandem cells3,4. By exploiting the nanoscale discretely distributed LiF ultrathin layer followed by an additional deposition of diammonium diiodide molecule, we have devised a bilayer intertwined passivation strategy that combines efficient electron extraction with further suppression of nonradiative recombination. We constructed perovskite-silicon tandem devices on double-side textured Czochralski (CZ)-based silicon heterojunction cell, which featured a mildly-textured front surface and a heavily-textured rear surface, leading to simultaneously enhanced photocurrent and uncompromised rear passivation. The resulting perovskite-silicon tandem achieved an independently certified stabilized PCE of 33.89%, accompanied by an impressive fill factor (FF) of 83.0% and an open-circuit voltage (Voc) of nearly 1.97 volts. To our knowledge, this represents the first reported certified efficiency of a two-junction tandem solar cell exceeding the single-junction Shockley-Queisser limit of 33.7%.

3.
Front Public Health ; 12: 1436423, 2024.
Article in English | MEDLINE | ID: mdl-39228843

ABSTRACT

Objective: This study aimed to assess the knowledge, attitudes, and practices (KAP) among family caregivers of patients with cerebral infarction toward home-based care. Methods: This web-based cross-sectional study was conducted between October 2023 and February 2024 at Yancheng Third People's Hospital. A self-designed questionnaire was developed to collect demographic information, and assess the KAP among family caregivers of patients with cerebral infarction toward home-based care. Results: A total of 761 questionnaires were included in the study. Among the participants, 453 (59.53%) were female, and 548 (72.01%) lived with the patients. The mean knowledge, attitudes and practices scores were 6.67 ± 1.73 (possible range: 0-9), 32.95 ± 2.46 (possible range: 9-45), and 28.64 ± 4.39 (possible range: 8-40), respectively. Path analysis showed the direct effect of knowledge on both attitudes (ß = 0.885, p < 0.001) and practices (ß = 1.295, p < 0.001), as well as of attitudes on practices (ß = 0.838, p < 0.001). Conclusion: Family caregivers of patients with cerebral infarction have sufficient knowledge, positive attitudes and proactive practices toward home-based care. However, they still exhibit deficiencies in certain aspects of knowledge, attitudes, and practice. Developing personalized educational strategies may be instrumental in enhancing family caregivers' knowledge of home-based care. This, in turn, could improve their attitudes and elevate their practice levels.


Subject(s)
Caregivers , Cerebral Infarction , Health Knowledge, Attitudes, Practice , Home Care Services , Humans , Female , Caregivers/psychology , Male , Cross-Sectional Studies , Middle Aged , Surveys and Questionnaires , Aged , Adult , China
4.
World J Clin Cases ; 12(22): 5151-5158, 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39109014

ABSTRACT

BACKGROUND: The common cause of sodium nitrite poisoning has shifted from previous accidental intoxication by exposure or ingestion of contaminated water and food to recent alarming intentional intoxication as an employed method of suicide/exit. The subsequent formation of methemoglobin (MetHb) restricts oxygen transport and utilization in the body, resulting in functional hypoxia at the tissue level. In clinical practice, a mismatch of cyanotic appearance and oxygen partial pressure usually contributes to the identification of methemoglobinemia. Prompt recognition of characteristic mismatch and accurate diagnosis of sodium nitrite poisoning are prerequisites for the implementation of standardized systemic interventions. CASE SUMMARY: A pregnant woman was admitted to the Department of Critical Care Medicine at the First Affiliated Hospital of Harbin Medical University due to consciousness disorders and drowsiness 2 h before admission. Subsequently, she developed vomiting and cyanotic skin. The woman underwent orotracheal intubation, invasive mechanical ventilation (IMV), and correction of internal environment disturbance in the ICU. Her premature infant was born with a higher-than-normal MetHb level of 3.3%, and received detoxification with methylene blue and vitamin C, supplemental vitamin K1, an infusion of fresh frozen plasma, as well as respiratory support via orotracheal intubation and IMV. On day 3 after admission, the puerpera regained consciousness, evacuated the IMV, and resumed enteral nutrition. She was then transferred to the maternity ward 24 h later. On day 7 after admission, the woman recovered and was discharged without any sequelae. CONCLUSION: MetHb can cross through the placental barrier. Level of MetHb both reflects severity of the sodium nitrite poisoning and serves as feedback on therapeutic effectiveness.

5.
Turk J Gastroenterol ; 35(6): 497-504, 2024 02 29.
Article in English | MEDLINE | ID: mdl-39101697

ABSTRACT

Background/Aims: Recent studies revealed that patients with persistent aminotransferase elevations after antiviral treatment had higher risk of hepatic events; yet its underlying causes remain unclear. Our study aimed to investigate the etiologies of persistent aminotransferase elevations in patients treated with nucleos(t)ide analogs (NAs). Materials and Methods: A retrospective study was conducted on chronic hepatitis B (CHB) patients who had been receiving NA treatment for over a year and had an aminotransferase level greater than 40 IU/mL (more than twice, with a 3-month interval) and subsequently underwent a liver biopsy. Results: The study group included 46 patients (34 males) with a mean age of 44.8 ± 20.3 years (range: 24-71 years).The average dura- tion of NA therapy was 3.7 years (1.1-10.6 years). The etiologies of persistant transaminase elevation were categorized into 4 groups: patients with low hepatitis B virus (HBV) viral load (LVL, n = 11); concurrent non-alcoholic fatty liver disease (NAFLD, n = 12); concurrent other liver diseases (OLD, n = 12); and unknown liver dysfunction (ULD, n = 11). The proportion of G ≥ 2 inflammation was significantly higher in the LVL group (90.9%) compared to NAFLD (33.3%), OLD (50%), and ULD (27.2%) groups (P = .012). The hepatitis B e-antigen (HBeAg)-positive group exhibited a younger age (34.5 ± 10.2 vs. 48.1 ± 9.4 years, P < .001), a lower proportion of fibrosis F ≥ 2 (36.3% vs. 77.1%, P = .012), and a higher prevalence of detectable HBV DNA (54.5% vs.14.2%, P = .00632) compared to the HBeAg-negative group. Conclusion: The etiology of persistent aminotransferase elevations in CHB patients undergoing NAs treatment warrants investigation. Besides the commonly observed NAFLD and low HBV viral load, concurrent presence of other liver diseases requires elucidation.The proportion of G≥2 inflammation was higher in the LVL group.


Subject(s)
Alanine Transaminase , Antiviral Agents , Hepatitis B, Chronic , Viral Load , Humans , Male , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/blood , Hepatitis B, Chronic/virology , Female , Middle Aged , Adult , Retrospective Studies , Antiviral Agents/therapeutic use , Antiviral Agents/adverse effects , Aged , Young Adult , Alanine Transaminase/blood , Hepatitis B virus , Liver/pathology , Non-alcoholic Fatty Liver Disease , Nucleosides/therapeutic use
6.
Article in English | MEDLINE | ID: mdl-39113679

ABSTRACT

Purpose: To describe the anatomical and histological characteristics of the human MTL (meniscotibial ligament) that keeps the meniscus stable and are rarely discussed. Study design: Descriptive laboratory study. Methods: In total, six fresh-frozen adult cadaver knees were dissected, and the dissection protocol were designed by two experienced anatomy professors. The anatomical morphology of MTL was observed. The main anatomical specimens included meniscus, tibial plateau, MTL. The osteotome was used to excise the portion of the tibial plateau, which could obtain the complex including partial meniscus, MTL, and a tibial fragment. A histopathologic study was performed by two experienced pathologists. Results: Macroscopically, the MTL could be divided into two parts: medial meniscotibial ligament (MMTL)and lateral meniscotibial ligament (LMTL). The MMTL is distributed continuously, whereas the LMTL is discontinuous on the tibial plateau. The average length from the tibial attachment of the LMTL to the articular surface was 19 ± 1.0mm (mean ± SD). The average length from the tibial attachment of the MMTL to the articular surface was 10 ± 1.2 mm (mean ± SD). Microscopy of the MTL showed that the MTL is a ligamentous tissue, composed of a network of oriented collagenous fibers. Conclusions: In all knees, the MTL was inserted on the outer edge of the meniscus, attaching to the tibia below the level of articular cartilage, which was key to maintaining the rotational stability of knee and the meniscus in the physiological position on the tibial plateau. Histological analysis of this ligament demonstrated that the MTL is a veritable ligamentous structure, which is made up of collagen type I-expressing fibroblasts. Clinical relevance: This article contributes to the understanding of the anatomical and histological characteristics of the MTL. It is beneficial to promote the development of relevant surgical techniques for the MTL lesion.

7.
Mol Divers ; 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39117890

ABSTRACT

Given the critical necessity for the development of more potent anti-cancer drugs, a series of novel compounds incorporating trifluoromethyl groups within the privileged 2-anilinoquinoline scaffold was designed, synthesized, and subjected to biological evaluation through a pharmacophore hybridization strategy. Upon evaluating the in vitro anti-cancer characteristics of the target compounds, it became clear that compound 8b, which contains a (4-(piperazin-1-yl)phenyl)amino substitution at the 2-position of the quinoline skeleton, displayed superior efficacy against four cancer cell lines by inducing apoptosis and cell cycle arrest. Following research conducted in a PC3 xenograft mouse model, it was found that compound 8b exhibited significant anti-cancer efficacy while demonstrating minimal toxicity. Additionally, the analysis of a 217-kinase panel pinpointed SGK1 as a potential target for this compound class with anti-cancer capabilities. This finding was further verified through molecular docking analysis and cellular thermal shift assays. To conclude, our results emphasize that compound 8b can be used as a lead compound for the development of anti-cancer drugs that target SGK1.

8.
PLoS One ; 19(8): e0308570, 2024.
Article in English | MEDLINE | ID: mdl-39116157

ABSTRACT

BACKGROUND: Tumor burden score (TBS) based on maximum tumor diameter and number has been shown to correlate with prognosis in patients with hepatocellular carcinoma (HCC). Nevertheless, the results are conflicting. Hence, we conducted a meta-analysis to analyze the association between TBS and survival outcomes of HCC patients. METHODS: A comprehensively search of the databases including PubMed, Embase and Web of Science was performed to retrieve studies satisfying the inclusion criteria until August 31, 2023. The hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. All the data analyses were carried out by STATA 12.0. RESULTS: 10 retrospective studies containing 25073 patients were incorporated in the study. The results demonstrated that high TBS was markedly association with poor overall survival (OS) (HR: 1.79, 95% CI: 1.45-2.23) and relapse-free survival / progression-free survival(RFS/PFS) (HR: 1.71; 95% CI: 1.42-2.07). Subgroup analysis showed that the prognostic value of TBS in HCC was not affected by any subgroup. CONCLUSIONS: TBS may be an efficient prognostic index in HCC patients.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Tumor Burden , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/diagnosis , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Humans , Prognosis , Retrospective Studies
9.
Fish Shellfish Immunol ; 153: 109821, 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39117129

ABSTRACT

Polymeric immunoglobulin receptor (pIgR) is an important immune factor in the mucosal immune system of fish, which plays a key role in mediating the secretion and transport of immunoglobulin into mucus. In this study, the full-length cDNA sequence of Megalobrama amblycephala pIgR gene was firstly cloned and the immune response to Aeromonas hydrophila was detected. After being challenged by Aeromonas hydrophila at 3 d, significantly pathological features were observed in intestine, head kidney, spleen, liver and gill of Megalobrama amblycephala. The content of lysozyme (Lys) and the activities of acid phosphatase (ACP) and alkaline phosphatase (AKP) increased significantly at 1 d and reached the peak at 3 d, and the activities of total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-PX) and catalase (CAT) in serum reached the peak at 5 d and 7 d after infection, respectively. The expression level of IL-1ß gene reached the peak at 3 d in intestine, 5 d in gill and spleen, 7 d in head kidney and liver of Megalobrama amblycephala after infected by Aeromonas hydrophila, respectively. The TNF-α gene expression reached the peak at 3 d in intestine and gill, 5 d in head kidney and spleen, 7 d in liver after infection, respectively. The experimental results showed that the infection of Aeromonas hydrophila caused the pathological changes of immune-related tissues and triggered the inflammation responses. The full-length cDNA sequence of Megalobrama amblycephala pIgR was 1828 bp, and its open reading frame (ORF) was 1023 bp, encoding 340 amino acids. The pIgR of Megalobrama amblycephala has a signal peptide sequence, followed by extracellular region, transmembrane region and intracellular region. The extracellular region includes two Ig-like domains (ILDs), and its tertiary structure is twisted "L". The phylogenetic tree was constructed using the adjacency method, and the pIgR genes of Megalobrama amblycephala and cyprinidae fish were clustered into a single branch. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of pIgR gene in different tissues of Megalobrama amblycephala. The expression level of pIgR gene was the highest in liver, followed by intestine, head kidney, skin, middle kidney and spleen, lower in heart, gill and brain, and the lowest in muscle. After being infected by Aeromonas hydrophila, the expression level of Megalobrama amblycephala pIgR gene in intestine, head kidney, spleen, liver and gill showed a trend of increasing first and then decreasing within 28 d. The pIgR gene expression reached the peak in mucosal immune-related tissues (gill and intestine) was earlier than that in systemic immune-related tissues (head kidney and spleen), and the relative expression level of pIgR gene at peak in intestine (12.3 fold) was higher than that in head kidney (3.73 fold) and spleen (7.84 fold). These results suggested that Megalobrama amblycephala pIgR might play an important role in the mucosal immune system to against Aeromonas hydrophila infection.

10.
World J Gastrointest Oncol ; 16(8): 3376-3381, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39171173

ABSTRACT

Long non-coding RNAs (lncRNAs), with transcript lengths exceeding 200 nucleotides and little or no protein-coding capacity, have been found to impact colorectal cancer (CRC) through various biological processes. LncRNA expression can regulate autophagy, which plays dual roles in the initiation and progression of cancers, including CRC. Abnormal expression of lncRNAs is associated with the emergence of chemoresistance. Moreover, it has been confirmed that targeting autophagy through lncRNA regulation could be a viable approach for combating chemoresistance. Two recent studies titled "Human ß-defensin-1 affects the mammalian target of rapamycin pathway and autophagy in colon cancer cells through long non-coding RNA TCONS_00014506" and "Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription" revealed novel insights into lncRNAs associated with autophagy and oxaliplatin resistance in CRC, respectively. In this editorial, we particularly focus on the regulatory role of lncRNAs in CRC-related autophagy and chemoresistance since the regulation of chemotherapeutic sensitivity by intervening with the lncRNAs involved in the autophagy process has become a promising new approach for cancer treatment.

11.
Math Biosci Eng ; 21(7): 6608-6630, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39176411

ABSTRACT

Feature representations with rich topic information can greatly improve the performance of story segmentation tasks. VAEGAN offers distinct advantages in feature learning by combining variational autoencoder (VAE) and generative adversarial network (GAN), which not only captures intricate data representations through VAE's probabilistic encoding and decoding mechanism but also enhances feature diversity and quality via GAN's adversarial training. To better learn topical domain representation, we used a topical classifier to supervise the training process of VAEGAN. Based on the learned feature, a segmentor splits the document into shorter ones with different topics. Hidden Markov model (HMM) is a popular approach for story segmentation, in which stories are viewed as instances of topics (hidden states). The number of states has to be set manually but it is often unknown in real scenarios. To solve this problem, we proposed an infinite HMM (IHMM) approach which utilized an HDP prior on transition matrices over countably infinite state spaces to automatically infer the state's number from the data. Given a running text, a Blocked Gibbis sampler labeled the states with topic classes. The position where the topic changes was a story boundary. Experimental results on the TDT2 corpus demonstrated that the proposed topical VAEGAN-IHMM approach was significantly better than the traditional HMM method in story segmentation tasks and achieved state-of-the-art performance.

12.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(8): 795-802, 2024 Aug 15.
Article in Chinese | MEDLINE | ID: mdl-39148382

ABSTRACT

The "Guidelines for parenteral nutrition in preterm infants: the American Society for parenteral and enteral nutrition" were developed by the American Society for Parenteral and Enteral Nutrition and published in the Journal of Parenteral and Enteral Nutrition in September 2023. The guidelines provide recommendations on 12 key clinical questions regarding parenteral nutrition (PN) for preterm infants. In comparison to similar guidelines, this set offers more detailed perspectives on PN for preterm infants. It presents evidence-based recommendations for the commencement time, nutrient dosage, and composition of PN, considering primary outcomes such as growth and development, as well as secondary outcomes like sepsis, retinopathy of prematurity, parenteral nutrition-related liver disease, and jaundice. This article aims to interpret the guidelines to provide a reference for colleagues in the field.


Subject(s)
Enteral Nutrition , Infant, Premature , Parenteral Nutrition , Practice Guidelines as Topic , Humans , Parenteral Nutrition/standards , Parenteral Nutrition/methods , Infant, Newborn , Enteral Nutrition/standards , Enteral Nutrition/methods , Societies, Medical
13.
World J Psychiatry ; 14(8): 1165-1173, 2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39165558

ABSTRACT

Patients with hematological tumors experience physical and psychological stress, and negative psychological states. Baduanjin, an emerging psychological rehabilitation method combined with resistance exercise, has received widespread attention. This study reviews the current status of the application of Baduanjin combined with resistance exercise in improving the negative psychological state of patients with hematological tumors and discusses its problems and prospects. Through a literature review and comprehensive analysis, the application of Baduanjin and resistance exercise in the psychological rehabilitation of patients with hematological tumors was identified and evaluated. The results showed that Baduanjin with resistance exercise had a positive effect on improving negative psychological states of patients with hematological tumors, which can alleviate anxiety, depression, and other adverse emotions, and improve quality of life. However, there is a lack of unified and standardized exercise intervention programs for practical application, and patient participation and compliance must be improved. Baduanjin combined with resistance exercise can potentially improve the negative psychological status of patients with hematological tumors; however, it is still necessary to further standardize and improve the exercise program improving patient participation and compliance. Future studies should strengthen theoretical exploration and empirical research, providing more effective psychological rehabilitation strategies for patients with hematological tumors.

14.
Chem Commun (Camb) ; 2024 Aug 22.
Article in English | MEDLINE | ID: mdl-39171688

ABSTRACT

We designed two series of NIR-II PTAs with D-A or D-A-D structures, in which the introduction of thiophene promotes a bathochromic shift of emission into the NIR-II region, helps to improve the cellular uptake of the PTAs and facilitates NIR-II imaging-guided PDT/PTT cancer phototherapy.

15.
Eye Contact Lens ; 50(9): 375-383, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39133174

ABSTRACT

OBJECTIVES: The aim of this study was to analyze the effects of lens deviation on peripheral defocus and optic quality in adolescents with moderate and severe myopia. METHODS: This prospective study enrolled 81 children (81 eyes). The spherical equivalent was -5.0≤SE≤-6.0 diopter. The participants were divided into two subgroups based on their eccentricity (inferior temporal) after wearing the lenses for 12 months. Between them, the low eccentric subgroup (A) had a total eccentric distance of less than 0.5 mm, and the moderate and severe eccentric subgroup (B) had a total eccentric distance of ≥0.5 mm. Peripheral defocus and eccentricity were measured before and after wearing the lenses, and the Spearman test was used to compare the parameters. RESULTS: Parameters such as the total peripheral defocus (TRDV) were significantly lower in subgroup B than in subgroup A after 12 months of orthokeratology lens usage. The axial length growth (ΔAL) in subgroup A was higher than that in subgroup B. Axial length growth, TRDV, and other parameters were significantly associated with eccentricity. The modulation transfer function cutoff and Strehl ratio were also significantly associated with eccentricity. CONCLUSIONS: Greater eccentricity within a certain range can induce greater periretinal defocus and improve the ΔAL.


Subject(s)
Myopia , Orthokeratologic Procedures , Refraction, Ocular , Visual Acuity , Humans , Adolescent , Prospective Studies , Female , Male , Myopia/physiopathology , Myopia/therapy , Child , Refraction, Ocular/physiology , Visual Acuity/physiology , Orthokeratologic Procedures/methods , Axial Length, Eye
16.
J Med Chem ; 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39145509

ABSTRACT

The activation of PP5 is essential for a variety of cellular processes, as it participates in a variety of biological pathways by dephosphorylating substrates. However, activation of PP5 by small molecules has been a challenge due to its native "self-inhibition" mechanism, which is controlled by the N-terminal TPR domain and the C-terminal αJ helix. Here, we reported the discovery of DDO-3733, a well-identified TPR-independent PP5 allosteric activator, which facilitates the dephosphorylation process of downstream substrates. Considering the negative regulatory effect of PP5 on heat shock transcription factor HSF1, pharmacologic activation of PP5 by DDO-3733 was found to reduce the HSP90 inhibitor-induced heat shock response. These results provide a chemical tool to advance the exploration of PP5 as a potential therapeutic target and highlight the value of pharmacological activation of PP5 to reduce heat shock toxicity of HSP90 inhibitors.

17.
Zhongguo Zhong Yao Za Zhi ; 49(14): 3706-3713, 2024 Jul.
Article in Chinese | MEDLINE | ID: mdl-39099345

ABSTRACT

Acupoint drug delivery is a traditional external therapy of traditional Chinese medicine(TCM). Guided by the meridian and collateral theory in TCM, it applies medications to the skin at acupoints, exerting a dual therapeutic effect by stimulating the acupoints and the conduction of meridians. Acupoint drug delivery is widely used in clinical practice. Different from traditional oral admi-nistration and injection, it absorbs medications through the skin, effectively avoiding the first-pass effect of drugs and the toxic side effects caused by injection. Acupoint selection and transdermal drug absorption are pivotal factors affecting the efficacy of acupoint drug delivery. Recent research on acupoint drug delivery mainly focuses on the evaluation of clinical efficacy, yet the systematic investigations on acupoint selection and pharmacodynamic factors are scarce. This study reviews the mechanism, efficacy evaluation and application status of acupoint drug delivery. It integrates the theory of TCM with modern medicine to explore the mechanism of acupoint drug delivery, evaluate its clinical efficacy, and assess the transdermal penetration in vivo and in vitro. The application status of acupoint drug delivery is also summarized, including the selection of acupoints, application dosage form, application time and the absorption of acupoints. This review aims to offer insights and references for the research, development and clinical application of acupoint drug delivery products.


Subject(s)
Acupuncture Points , Drug Delivery Systems , Humans , Drug Delivery Systems/methods , Animals , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/pharmacokinetics , Skin Absorption/drug effects , Meridians , Medicine, Chinese Traditional , Administration, Cutaneous
18.
J Oral Rehabil ; 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39101668

ABSTRACT

BACKGROUND: Syndecan 4 (SDC4), a type I transmembrane proteoglycan, serves as a critical link between chondrocytes and the extracellular matrix. OBJECTIVE: This study aimed to explore the role of SDC4 in cartilage degeneration of temporomandibular joint osteoathritis (TMJOA). METHODS: Condylar chondrocytes were stimulated with varying concentrations of recombinant rat interleukin-1ß (rrIL-1ß) and SDC4 small interfering RNA (si-SDC4). Anti-SDC4 ectodomain-specific antibodies or IgG were intra-articularly administrated in a TMJOA model rats. SDC4 conditional knockout (SDC4-cKO) and Sdc4flox/flox mice were induced TMJOA. Cartilage degeneration was assessed using haematoxylin & eosin (H&E) and safranin O (SO) staining. Protein levels of SDC4, matrix metalloproteinases (MMPs), a disintegrin and metalloproteinase with a thrombospondin motifs 5 (ADAMTS5), tumour necrosis factor α (TNFα), type II collagen (Col-II), aggrecan (ACAN), cleaved caspase 3 (CASP3), Ki67 and related pathways in condylar cartilage were evaluated by immunohistochemical (IHC) staining or western blot assays. RESULTS: SDC4 expression was evidently increased in MIA-model animals compared to control groups. rrIL-1ß stimulation increased the expression of SDC4, MMP3 and ADAMTS5 expression in chondrocytes, while decreasing the expression of Col-II. These effects were reversed by si-SDC4 in vitro. In vivo, SDC4 blockade reduced the death of chondrocytes and the loss of cartilage matrix, which was evidenced by increased expression of Col-II and ACAN, and a decrease in SDC4, MMP13 and cleaved-CASP3-positive cells. Furthermore, the protein levels of ACAN and Ki67 were elevated, and the ERK1/2 and P38 signalling pathways were activated following SDC4 inhibition. CONCLUSIONS: SDC4 inhibition significantly ameliorates condylar cartilage degeneration, which was mediated, at least partly, through P38 and ERK1/2 signalling. Inhibition of SDC4 may be of great value for the treatment of TMJOA.

19.
BMC Genomics ; 25(1): 797, 2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39179980

ABSTRACT

BACKGROUND: R2R3-MYB transcription factors belong to one of the largest gene subfamilies in plants, and they are involved in diverse biological processes. However, the role of R2R3-MYB transcription factor subfamily genes in the response of rice (Oryza sativa L.) to salt stress has been rarely reported. RESULTS: In this study, we performed a genome-wide characterization and expression identification of rice R2R3-MYB transcription factor subfamily genes. We identified a total of 117 R2R3-MYB genes in rice and characterized their gene structure, chromosomal location, and cis-regulatory elements. According to the phylogenetic relationships and amino acid sequence homologies, the R2R3-MYB genes were divided into four groups. qRT-PCR of the R2R3-MYB genes showed that the expression levels of 10 genes significantly increased after 3 days of 0.8% NaCl treatment. We selected a high expression gene OsMYB2-115 for further analysis. OsMYB2-115 was highly expressed in the roots, stem, leaf, and leaf sheath. OsMYB2-115 was found to be localized in the nucleus, and the yeast hybrid assay showed that OsMYB2-115 has transcriptional activation activity. CONCLUSION: This result provides important information for the functional analyses of rice R2R3-MYB transcription factor subfamily genes related to the salt stress response and reveals that OsMYB2-115 may be an important gene associated with salt tolerance in rice.


Subject(s)
Gene Expression Regulation, Plant , Oryza , Phylogeny , Plant Proteins , Salt Stress , Transcription Factors , Oryza/genetics , Oryza/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Salt Stress/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Genome, Plant , Multigene Family , Gene Expression Profiling , Chromosomes, Plant/genetics
20.
Chemistry ; : e202402402, 2024 Aug 26.
Article in English | MEDLINE | ID: mdl-39186035

ABSTRACT

Efficient metal-free synthesis of benzo[b]azepines and oxindoles is achieved via a radical relay cascade strategy employing halogen atom transfer (XAT) for aryl radical generation followed by intramolecular hydrogen atom transfer (HAT). Optimization yielded moderate to substantial yields under visible light irradiation. Preliminary biological assessments revealed promising anti-tumor activity for select compounds. This study underscores the potential of XAT-mediated radical relay cascades in medicinal chemistry and anticancer drug discovery.

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