Three new antinociceptive diterpenoids from the fruits of Rhododendron molle.

Investigation of the fruits of Rhododendron molle G. Don led to the isolation of three new grayanane-type diterpenoids, rhodomolleins LIV-LVI (1-3). The structures and absolute configurations of new compounds were fully elucidated by spectroscopic analysis and single-crystal X-ray diffraction, including HRESIMS, 1 D and 2 D NMR data. Compounds 1-3 were evaluated for analgesic activities utilizing an acetic acid-induced writhing test in mice. Compound 1 showed a significant antinociceptive effect with writhe inhibition rates of 72.9% and 100% at doses of 6 mg/kg and 20 mg/kg in mice, respectively. The binding mode of 1 to N-ethylmaleimide-sensitive factor (NSF, PDB: 6IP2) was explored by molecular docking, indicating the presence of hydrogen bond interactions which account for its analgesic activity.

A Comparative Study of Prevalence and Associated Factors of Social Support Among Chinese Shidu Parents and Non-Shidu Parents.

The number of parents in China who have lost their only child, referred to as shidu parents, currently exceeds one million and is increasing by approximately 76,000 annually. Shidu parents face a unique challenge in long-term care, primarily stemming from the sudden and tragic loss of their only child, which leads to a substantial decrease in their social support network. A multi-stage, stratified, and cluster sampling method was employed across various economic belts. Linear regression analysis was utilized to examine factors associated with the social support status of shidu and non-shidu parents. The level of social support decreases as the severity of depression increases. Shidu parents with grandchildren tend to have good social support. The city of Hangzhou exhibits relatively high levels of social support. Married individuals typically report higher levels of social support. It is recommended to prioritize shidu parents without grandchildren as a primary focus for government and societal support. Key recommendations include strengthening social skills training and developing social support networks. Drive economic development, particularly in relatively underdeveloped regions. Strengthen social organizations and community development. Enhancing access to support services, leveraging technology, and encouraging volunteerism for non-married parents.

Experimental evidence of ß-relaxation and its structural origin in ZIF-62 glass.

Intrinsic relaxation processes determine the crucial properties of glass, yet their underlying mechanisms are far from well understood. The brand-new glass-forming metal-organic frameworks (MOFs) provide desirable opportunities for looking inside glass relaxation, especially the secondary ß-relaxation phenomenon and mechanism. For a representative zeolitic imidazolate framework-62 (ZIF-62) glass, reliable and fine powder mechanical spectroscopy was performed based on home-made mountings combined with a commercial dynamical mechanical analyzer. For the first time, ß-relaxation was observed in a MOF glass besides the primary α-relaxation. The pronounced ß-relaxation was well demonstrated by a number of characteristics including an excess wing and the full width at half maximum (W) of the α-relaxation peaks, which deviated from the time-temperature superposition. The stretched exponent ß of ZIF-62 glass is 0.71 in the supercooled region. The W of ZIF-62 glass is the maximum among all known glassy materials. The structural origin of α- and ß-relaxation can be attributed to an increase of density, as observed using nuclear magnetic resonance (NMR). A general linear and broad correlation of fragility and stretched exponent ß with W of the α-relaxation peaks was established. When compared with traditional glass-formers, the resulting principles indicate a shared origin for the stretched exponent ß, W, and ß-relaxation in the case of ZIF-62 glass. The presented findings offer an effective new method to explore the glass/liquid transition of MOF glasses, which helps to obtain a deeper insight into the hierarchical relaxation dynamics of the glass transition.

The efficacy of Raman spectroscopy in lung cancer diagnosis: the first diagnostic meta-analysis.

In recent years, many researches have explored the diagnostic value of Raman spectroscopy in multiple types of tumors. However, as an emerging clinical examination method, the diagnostic performance of Raman spectroscopy in lung cancer remains unclear. Relevant diagnostic studies published before 1 June 2020 were retrieved from the Cochrane Library, PubMed, EMBASE, China National Knowledge Internet (CNKI), and WanFang databases. After the literature was screened, two authors extracted the data from eligible studies according to the inclusion and exclusion criteria. Obtained data were pooled and analyzed using Stata 16.0, Meta-DiSc 1.4, and RevMan 5.3 software. Fourteen diagnostic studies were eligible for the pooled analysis which includes 779 patients. Total pooled sensitivity and specificity of Raman spectroscopy in diagnosing lung cancer were 0.92 (95% CI 0.87-0.95) and 0.94 (95% CI 0.88-0.97), respectively. The positive likelihood ratio was 15.2 (95% CI 7.5-30.9), the negative likelihood ratio was 0.09 (95% CI 0.05-0.14), and the area under the curve was 0.97 (95 % CI 0.95-0.98). Subgroup analysis suggested that the sensitivity and specificity of RS when analyzing human tissue, serum, and saliva samples were 0.95 (95% CI 0.88-0.98), 0.97 (95% CI 0.89-0.99), 0.88 (95% CI 0.80-0.93), 0.87 (95% CI 0.78-0.92), 0.91 (95% CI 0.80-0.96), and 0.95 (95% CI 0.73-0.99), respectively. No publication bias or threshold effects were detected in this meta-analysis. This initial meta-analysis indicated that Raman spectroscopy is a highly specific and sensitive diagnostic technology for detecting lung cancer. Further investigations are also needed to focus on real-time detection using Raman spectroscopy under bronchoscopy in vivo. Moreover, large-scale diagnostic studies should be conducted to confirm this conclusion.

Antifungal Activity of Volatile Organic Compounds Produced by Bacillus methylotrophicus and Bacillus thuringiensis against Five Common Spoilage Fungi on Loquats.

Loquat fruit is one of the most perishable fruits in China, and has a very limited shelf life because of mechanical injury and microbial decay. Due to an increasing concern about human health and environmental security, antagonistic microorganisms have been a potential alternative for fungicides to control postharvest diseases. In this work, the antifungal effect of volatile organic compounds (VOCs) produced by Bacillus methylotrophicus BCN2 and Bacillus thuringiensis BCN10 against five postharvest pathogens isolated from loquat fruit, Fusarium oxysporum, Botryosphaeria sp., Trichoderma atroviride, Colletotrichum gloeosporioides, and Penicillium expansum were evaluated by in vitro and in vivo experiments. As a result, the VOCs released by BCN2 and BCN10 were able to suppress the mycelial growth of all targeted pathogens according to inhibition ratio in the double petri-dish assay as well as disease incidence and disease diameter on loquat fruits. The main volatile compounds were identified by solid-phase microextraction (SPME)-gas chromatography. These VOCs produced by the two strains played complementary roles in controlling these five molds and enabled loquat fruits to keep fresh for ten days, significantly. This research will provide a theoretic foundation and technical support for exploring the functional components of VOCs applicable in loquat fruit preservation.

Structural, antioxidant and adsorption properties of dietary fiber from foxtail millet (Setaria italica) bran.

BACKGROUND: Foxtail millet (Setaria italica) bran is a by-product of millet processing, rich in dietary fiber (DF) and has great application value. A comparative study was conducted to explore the differences in structural and functional properties among millet bran DF, soluble dietary fiber (SDF) and insoluble dietary fiber (IDF). RESULTS: There was a significant difference in the content of monosaccharides between SDF and IDF, in which xylose, arabinose and glucose were the main compositions. The results of scanning electron microscopy showed that DF and IDF had different forms of network structure, and SDF presented a sign of mutual adhesion. The total phenolic and flavonoid contents were 0.54 and 0.08 g kg-1 in SDF. Antioxidant activity of SDF was higher than that of IDF based on the evaluation of free radical scavenging and iron reducing capacity in vitro. Meanwhile, the glucose dialysis retardation index of IDF and SDF was 12.59% and 9.26% at 30 min, respectively. And, there was no significant difference in the adsorption capacity of glucose among different samples (P > 0.05). Furthermore, SDF had strong α-amylase inhibition (17.92% inhibition rate) and sodium cholate adsorption capacities; the adsorption amount was 16.76 g kg-1 in 2.00 g L-1 sodium cholate solution. CONCLUSION: Foxtail millet bran DF, especially SDF, has good functional properties and would be a suitable ingredient for health-beneficial food production. However, the relevant verification trials in vivo need to be carried out in the next steps. © 2019 Society of Chemical Industry.

Plasmonic band structures in doped graphene tubes.

We present theoretically the transport of plasmonic waves in doped graphene tube, which is made by rolling planar graphene sheet into a cylinder and periodic doping is applied on it. It is shown that periodic modulation of the Fermi level along the tube can open gaps in the dispersion relations of graphene plasmons and eventually create plasmonic band structures. The propagation of graphene plasmons is forbidden within the bandgaps; while within the band, the plasmonic waves present axially-extended field distributions and propagate along the tubes, yet well confined around the curved graphene surface. Furthermore, the bandgaps, propagation constants and propagation lengths of the modes in plasmonic band structures are significantly tuned by varying the Fermi level of graphene, which provides active controls over the plasmonic waves. Our proposed structures here may provide an approach to dynamically control the plasmonic waves in graphene-based subwavelength waveguides.

The Catsper channel and its roles in male fertility: a systematic review.

The Catsper channel is a sperm-specific, Ca2+-permeable, pH-dependent, and low voltage-dependent channel that is essential for the hyperactivity of sperm flagellum, chemotaxis towards the egg, capacitation and acrosome reaction. All of these physiological events require calcium entry into sperm cells. Remarkably, Catsper genes are exclusively expressed in the testis during spermatogenesis, and are sensitive to ion channel-induced pH change, such as NHEs, Ca2+ATPase, K+ channel, Hv1 channel and HCO3- transporters. Furthermore, the Catsper channel is regulated by some physiological stimulants, such as progesterone, cyclic nucleotides (e.g., cAMP, cGMP), zona pellucida (ZP) glycoproteins and bovine serum albumin (BSA). All of these factors normally stimulate Ca2+ entry into sperm through the Catsper channel. In addition, the Catsper channel may be a potential target for male infertility treatment or contraception. This review will focus on the structure, functions, regulation mechanisms and medicinal targets of the Catsper channel.

Diagnostic Values of sVEGFR-1 and Endostatin in Malignant Pleural Effusions in Patients with Lung Cancer.

BACKGROUND: The diagnosis of malignant pleural effusion (MPE) remains a common clinical challenge because of the sensitivity of conventional cytology for the detection is insufficient. Thus, a sensitive clinical marker for diagnosis is required. The aim of this study was to assess the role of two anti-angiogenic cytokines, soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and endostatin, in diagnosing MPE. METHODS: Effusion samples from 44 patients with MPE caused by lung cancer and from 36 patients with benign pleural effusion (BPE) were collected. The concentrations of sVEGFR-1 and endostatin in pleural fluid were determined by an enzyme-linked immunosorbent assay (ELISA). The diagnostic performance was measured by receiver operating characteristic curves (ROCs). RESULTS: The levels of sVEGFR-1 and endostatin in MPE due to lung cancer were significantly higher than those in BPE (p < 0.05). The sensitivity and specificity of endostatin were 52.27% and 86.11%, respectively, while for sVEGFR-1, the sensitivity was 88.64% and the specificity was 58.33%. Interestingly, the combination of sVEGFR1 and endostatin produced better sensitivity and specificity of 72.73% and 83.33%, respectively. In addition, the levels of sVEGFR-1 and endostatin were significantly related to each other (p < 0.05), and the levels of endostatin in bloody effusions were significantly higher than those in non-bloody effusions (p < 0.05). CONCLUSIONS: Our study indicated that the levels of sVEGFR-1 and endostatin were significantly elevated in MPE. The combined detection of sVEGFR-1 and endostatin may be useful in the diagnosis of MPE.

Association of dietary and serum vitamin E with bone mineral density in middle-aged and elderly Chinese adults: a cross-sectional study.

Previous studies have suggested that vitamin E (VE) may affect bone health, but the findings have been inconclusive. We examined the relationship between VE status (in both diet and serum) and bone mineral density (BMD) among Chinese adults. This community-based study included 3203 adults (2178 women and 1025 men) aged 40-75 years from Guangzhou, People's Republic of China. General and dietary intake information were collected using structured questionnaire interviews. The serum α-tocopherol (TF) level was quantified by reversed-phase HPLC. The BMD of the whole body, the lumbar spine and left hip sites (total, neck, trochanter, intertrochanter and Ward's triangle) were measured using dual-energy X-ray absorptiometry. In women, the dietary intake of VE was significantly and positively associated with BMD at the lumbar spine, total hip, intertrochanter and femur neck sites after adjusting for covariates (P(trend): 0·001-0·017). Women in quartile 3 of VE intake typically had the highest BMD; the covariate-adjusted mean BMD were 2·5, 3·06, 3·41 and 3·54% higher, respectively, in quartile 3 (v. 1) at the four above-mentioned sites. Similar positive associations were observed between cholesterol-adjusted serum α-TF levels and BMD at each of the studied bone sites (P(trend): 0·001-0·022). The covariate-adjusted mean BMD were 1·24-4·83% greater in quartile 4 (v. 1) in women. However, no significant associations were seen between the VE levels (dietary or serum) and the BMD at any site in men. In conclusion, greater consumption and higher serum levels of VE are associated with greater BMD in Chinese women but not in Chinese men.

Serum betaine is inversely associated with low lean mass mainly in men in a Chinese middle-aged and elderly community-dwelling population.

Previous studies have demonstrated that betaine supplements increase lean body mass in livestock and improve muscle performance in human beings, but evidence for its effect on human lean mass is limited. Our study assessed the association of circulating betaine with lean mass and its composition in Chinese adults. A community-based study was conducted on 1996 Guangzhou residents (weight/mass: 1381/615) aged 50-75 years between 2008 and 2010. An interviewer-administered questionnaire was used to collect general baseline information. Fasting serum betaine was assessed using HPLC-MS. A total of 1590 participants completed the body composition analysis performed using dual-energy X-ray absorptiometry during a mean of 3·2 years of follow-up. After adjustment for age, regression analyses demonstrated a positive association of serum betaine with percentage of lean mass (LM%) of the entire body, trunk and limbs in men (all P<0·05) and LM% of the trunk in women (P=0·016). Each sd increase in serum betaine was associated with increases in LM% of 0·609 (whole body), 0·811 (trunk), 0·422 (limbs), 0·632 (arms) and 0·346 (legs) in men and 0·350 (trunk) in women. Multiple logistic regression analysis revealed that the prevalence of lower LM% decreased by 17 % (whole body) and 14 % (trunk) in women and 23 % (whole body), 28 % (trunk), 22 % (arms) and 26 % (percentage skeletal muscle index) in men with each sd increment in serum betaine. Elevated circulating betaine was associated with a higher LM% and lower prevalence of lower LM% in middle-aged and elderly Chinese adults, particularly men.

A landscape of methodology and implementation of adaptive designs in cancer clinical trials.

BACKGROUND: The use of adaptive designs in cancer trials has considerably increased worldwide in recent years, along with the release of various guidelines for their application. This systematic review aims to comprehensively summarize the key methodological and executive features of adaptive designs in cancer clinical trials. METHODS: A comprehensive search from PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials was conducted to screen eligible clinical trials that employed adaptive designs and were conducted in cancer patients. The methodological and executive characteristics of adaptive designs were the main measurements extracted. Descriptive analyses, primarily consisting of frequency and percentage, were employed to analyzed and reported the data. RESULTS: A total of 180 cancer clinical trials with adaptive designs were identified. The first three most common type of adaptive design was the group sequential design (n=114, 63.3 %), adaptive dose-finding design (n=22, 12.2 %), and adaptive platform design (n=16, 8.9 %). The results showed that 4.4 % (n=8) of trials conducted post hoc modifications, and around 29.4 % (n=53) did not provide the methods for controlling type I errors. Among phase II or above trials, 79.9 % (112/140) applied the surrogate endpoint as the primary outcome in these trials. Importantly, 27.2 % (49/180) of trials did not report clear information on the independent data monitoring committee (iDMC), and 13.3 % (n=24) without clear information on interim analyses. Interim analyses suggested 34.4 % (62/180) of trials being stopped for futility, 10.6 % (n=19) for efficacy, and 2.2 % (n=4) for safety concerns in the early stage. CONCLUSIONS: This study emphasizes adaptive designs in cancer trials face significant challenges in their design or strict implementation according to protocol, which might significantly compromise the validity and integrity of trials. It is thus important for researchers, sponsors, and policymakers to actively oversee and guide their application.

Geriatric nutrition risk index: a more powerful index identifying muscle mass loss in patients with rheumatoid arthritis.

OBJECTIVE: To explore the association of geriatric nutrition risk index (GNRI), a traditional albumin-body weight calculation, with myopenia in patients with rheumatoid arthritis (RA) and compare its ability to identify myopenia with protein indicators. METHODS: This cross-sectional study was carried out based on a Chinese RA cohort. Clinical data and protein indicators (including albumin, globulin, albumin to globulin ratio, prealbumin, hemoglobin) were collected. GNRI was estimated by serum albumin and body weight. Myopenia was indicated as muscle mass loss measured by bioelectric impedance analysis. RESULTS: There were 789 RA patients included with mean age 52.6 ± 12.6 years and 77.6% female. There were 41.3%, 18.0%, 27.5%, 13.2% patients with no (GNRI > 98), low (GNRI 92 to ≤ 98), moderate (GNRI 82 to < 92), and major nutrition-related risk (GNRI < 82). There were 406 (51.5%) RA patients with myopenia, RA patients with major nutrition-related risk had the highest prevalence of myopenia (87.5% vs. 73.3% vs. 50.0% vs. 26.1%). Multivariate logistic analysis showed that compared with no risk, RA patients with low (OR = 3.23, 95% CI: 1.86-5.61), moderate (OR = 9.56, 95% CI: 5.70-16.01), and major nutrition-related risk (OR = 28.91, 95% CI: 13.54-61.71) were associated with higher prevalence of myopenia. Receiver operating characteristic curves showed that GNRI (AUC = 0.79) performed a better identifiable ability toward myopenia than serum albumin (AUC = 0.66) or others indicators (AUC range 0.59 to 0.65), respectively. CONCLUSION: GNRI, an objective and convenient albumin-weight index, may be preferable for identifying myopenia in RA patients. Key Points • We firstly elucidated the association of GNRI with muscle mass loss among RA patients, and compared its ability to identify muscle mass loss with serum albumin or other protein indicators. • Major nutrition-related risk identified by GNRI showed the highest risk of muscle mass loss, GNRI demonstrated a greater ability to identify myopenia in RA patients. which indicated GNRI was an objective and convenient albumin-weight index to identify myopenia in RA patients.

A novel classification of tracheal defects and the reconstruction strategies: A retrospective study based on 106 cases.

Objective: The study aims to present a novel classification of tracheal defects and the corresponding reconstruction strategies. Methods: The retrospective study was designed to analyze patients with diagnosed primary or secondary tracheal tumors from 1991 to 2020. Surgical techniques, complications and prognosis were reviewed. Airway status and patient outcomes were the principal follow-up measures. Tracheal defects were classified into two plane sizes (vertical (V) and horizontal (H) planes). Vertical defects were further categorized into three groups based on their tracheal ring numbers (V1, ≤ 5 rings; V2, 6-10 rings; and V3, > 10 rings). Tracheal defects with horizontal plane size H1 and H2 represent defects less and more than one-half the circumference of trachea. Thus, suitable reconstruction strategies were planned primarily based on "V" and "H" classifications. The reconstruction strategies performed were sleeve resection followed by an end-to-end anastomosis, window resection with sternocleidomastoid myoperiosteal flap reconstruction, defects conversion with rotation anastomosis, and modified tracheostomy with secondary flap reconstruction. Results: A total of 106 patients diagnosed with tracheal defects were enrolled in the study, of whom 59 patients underwent sleeve resection followed by end-to-end anastomosis; 40 patients received window resection alongside sternocleidomastoid (SCM) myoperiosteal flap reconstruction; five patients received converting defects with rotation anastomosis and two patients underwent modified tracheostomy with secondary stage flap reconstruction. Lumen stenosis occurred in three V2H1 defect cases and were treated by a second reconstruction surgery. Iatrogenic unilateral recurrent laryngeal nerve paralysis occurred in two patients with the V3H2 defect type, who were treated by temporary tracheotomy and partial vocal cord resection and extubated successfully during follow-up. All 106 patients achieved airway patency with adequate laryngeal function at the end of follow-up. No anastomotic dehiscence or bleeding occurred in any patient postoperatively. Conclusion: Though a significant number of multicenter studies concerning the reconstruction and classification of tracheal defects are needed, the study herein provides a novel classification of tracheal defects, which is primarily developed on the defect size. Therefore, the study might serve as a potential source for identifying suitable reconstruction strategies for practitioners.

Multi-trajectories of health-related quality of life and their associated factors in patients with nasopharyngeal carcinoma: A longitudinal study.

BACKGROUND: The trajectories of health-related quality of life (HRQoL) of nasopharyngeal carcinoma (NPC) during and after the treatment along with their associated factors are seldom investigated in longitudinal studies. This study aims to investigate the longitudinal trajectories of HRQoL over time and their associated factors in patients with newly diagnosed NPC. METHODS: Between July 2018 and September 2019, a total of 500 patients were finally involved in this study. HRQoL was measured at four time points, from before treatment to the follow-up period after treatment. Group-based multi-trajectory modeling was applied to identify trajectories of five HRQoL functioning domains during the longitudinal period. Multinomial logistic regression models were applied to investigate potential independent factors associated with the multi-trajectory groups. RESULTS: We identified four distinct multi-trajectory groups, including the "initially lowest functioning" group (19.8%), the "initially lower functioning" group (20.8%), the "initially higher functioning" group (46.0%), and the "consistently highest functioning" group (13.4%). Patients who were older than 45 years or had T4 stage disease were more likely to be in the "initially lowest functioning" group, while those with EBV DNA ≥ 1500 copies/mL before the treatment were more likely to be in the "initially lowest functioning" or the "initially lower functioning" groups. CONCLUSIONS: We report the presence of heterogeneity in HRQoL trajectories among patients with NPC, and found that older age, advanced T stage, and higher EBV DNA level before treatment were significantly associated with poor HRQoL trajectories. Further studies are needed to examine the generalizability of these identified HRQoL trajectories and their associations with psychosocial and survival outcomes.

Antibody responses to an inactivated SARS-CoV-2 vaccine in individuals aged from 50 to 102 years.

Objectives: To assess antibody responses to an inactivated SARS-CoV-2 vaccine in individuals aged 50 and older. Methods: We conducted a post-market cross-sectional seroepidemiology study. We recruited 4,632 vaccinated individuals aged 50 and older, measured their total serum SARS-CoV-2-specific antibody (TA), and collected correlates. The primary outcome was the geometric mean titer (GMT) of TA, and the secondary outcome was the decline of TA with age. Univariate, bivariate, and multivariate analyses were used to examine the associations of the TA GMT with age, and trend analyses were used to test whether their associations were significant. Results: All participants had a detectable TA, which was generally at a low level across all age groups. The TA GMT (95% CI) in AU/mL was 3.05 (2.93, 3.18); the corresponding arithmetic mean (95% CI) was 17.77 (16.13, 19.42) in all participants and 4.33 (3.88, 4.84), 3.86 (3.49, 4.28), 3.24 (2.92, 3.59), 2.77 (2.60, 2.96), and 2.65 (2.48, 2.83) in the age groups of 50-54, 55-59, 60-64, 65-74, and 75 years or older, respectively. The TA GMT decreased with age with a P trend < 0.001. The TA GMT was significantly lower in those with hypertension or diabetes compared to those with neither. Conclusion: The inactivated SARS-CoV-2 vaccine is effective in individuals aged 50 and older. This is the first study that has found an inverse dose-response relationship between ages and the low-level TAs. Older people, especially those with chronic diseases, should get the SARS-CoV-2 vaccine, and their vaccination frequency, dose, and method may need to be different from those of younger people.

[Analysis of clinical characteristics of partial olfactory dysfunction].

OBJECTIVE: To apply different types and concentrations of T&T olfactometer odorants to exam smell function and explore the clinical characteristics of partial olfactory dysfunction. METHODS: From March 2007 to May 2008, a total of 24 patients with olfactory dysfunction were examined by medical and psychiatric history enquiry, physical examination, smell testing and medical imaging. Olfactory function of each nostril was assessed separately by T&T olfactometer. The test contained five kinds of odorants at different concentrations. Recognition threshold (RT) scores for all five odorants and for each individual odorant were measured in all patients. RESULTS: Among them, total RT scores were normal while single odorant testing yielded only significant higher RT scores for one or two odorants. For patients who suffered partial olfactory dysfunction, 51.4% are for pleasant odors, while the rest are for unpleasant odors. CONCLUSION: Normal total RT scores and abnormal single RT scores of T&T olfactometer are present in partial olfactory dysfunction. As a special clinical manifestation of olfactory disorder, it may be easily ignored in smell testing.

Novel 1,2,3-Triazole Erlotinib Derivatives as Potent IDO1 Inhibitors: Design, Drug-Target Interactions Prediction, Synthesis, Biological Evaluation, Molecular Docking and ADME Properties Studies.

Indoleamine 2,3-dioxygenase 1 (IDO1) plays a predominant role in cancer immunotherapy which catalyzes the initial and rate limiting steps of the kynurenine pathway as a key enzyme. To explore novel IDO1 inhibitors, five derivatives of erlotinib-linked 1,2,3-triazole compounds were designed by using a structure-based drug design strategy. Drug-target interactions (DTI) were predicted by DeePurpose, an easy-to-use deep learning library that contains more than 50 algorithms. The DTI prediction results suggested that the designed molecules have potential inhibitory activities for IDO1. Chemical syntheses and bioassays showed that the compounds exhibited remarkable inhibitory activities against IDO1, among them, compound e was the most potent with an IC50 value of 0.32 ± 0.07 µM in the Hela cell assay. The docking model and ADME analysis exhibited that the effective interactions of these compounds with heme iron and better drug-likeness ensured the IDO1 inhibitory activities. The studies suggested that compound e was a novel and interesting IDO1 inhibitor for further development.

DNTTIP2 Expression is Associated with Macrophage Infiltration and Malignant Characteristics in Low-Grade Glioma.

Purpose: Low-grade gliomas (LGG) are primary brain tumors that often affect predominantly young adults, which usually have a painless course, and have a longer survival period compared to patients with high-grade gliomas. Relatively established treatment options include surgery, radiotherapy, chemotherapy or combination therapy, as well as individualized management based on tumor location, histology, molecular features and patient characteristics. Due to the rapid development of targeted therapies, the development of new molecular targets is now a very promising research direction. Methods: We explored the diagnostic value, clinical relevance, and molecular function of deoxynucleotidyl transferase terminal-interacting proteins 2 (DNTTIP2) in LGG using MethSurv, MEXPRESS, STRING, cBioPortal, Tumor Immunity Estimation Resource (TIMER) database, Gene Expression Profiling Interactive Analysis (GEPIA) databases. Besides, the "CIBERSORT" algorithm was conducted to estimate immune cells infiltration abundance, with "ggplot2" package visualizing the results. In vivo and vitro experiments were used to verify the speculations of bioinformatics analysis. Results: In LGG patients, DNTTIP1/2 were over-expressed at mRNA levels and high DNTTIP1/2 levels correlated with poor survival in LGG patients. We confirmed that DNTTIP2 significantly promotes M2 macrophage activation and angiogenesis, which may be related to the IL6/JAK/STAT3 signaling pathway. In addition, we found that DNTTIP2 amplification was associated with an unfavorable prognosis in LGG patients. We demonstrated, finally, a correlation between DNTTIP2 gene hypermethylation and a poor prognosis in LGG. Conclusion: This study demonstrated that DNTTIP1/2 had diagnostic and prognostic value in LGG patients. The biological mechanisms of DNTTIP2 regarding angiogenesis and macrophage activation may provide new insights into the treatment of glioma.

[Professor GAO Wei-bin's clinical experience of electroacupuncture with dense wave at periotic points for neurotic tinnitus].

Professor GAO Wei-bin's clinical experience of electroacupuncture (EA) with dense wave at periotic points for neurotic tinnitus is introduced. Based on the basic theory of TCM and the perspective of neuroanatomy, EA with dense wave at new periotic points (four points at mastoid process) and Ermen (TE 21), Tinggong (SI 19) could have the effects of qi reaching affected area, and play the treatment role of "where the acupoint is, where the efficacy is".