Neural correlates of impaired learning and recognition of novel faces in mild cognitive impairment.

OBJECTIVE: Face memory impairment significantly affects social interactions and daily functioning in individuals with mild cognitive impairment (MCI). While deficits in recognizing familiar faces among individuals with MCI have been reported, their ability to learn and recognize unfamiliar faces remains unclear. This study examined the behavioral performance and event-related potentials (ERPs) of unfamiliar face memorization and recognition in MCI. METHODS: Fifteen individuals with MCI and 15 healthy controls learned and recognized 90 unfamiliar neutral faces. Their performance accuracy and cortical ERPs were compared between the two groups across the learning and recognition phases. RESULTS: Individuals with MCI had lower accuracy in identifying newly learned faces than healthy controls. Moreover, individuals with MCI had reduced occipitotemporal N170 and central vertex positive potential responses during both the learning and recognition phases, suggesting impaired initial face processing and attentional resources allocation. Also, individuals with MCI had reduced central N200 and frontal P300 responses during the recognition phase, suggesting impaired later-stage face recognition and attention engagement. CONCLUSION: These findings provide neurobehavioral evidence for impaired learning and recognition of unfamiliar faces in individuals with MCI. SIGNIFICANCE: Individuals with MCI may have face memory deficits in both early-stage face processing and later-stage recognition .

Effects of rTMS treatment on global cognitive function in Alzheimer's disease: A systematic review and meta-analysis.

Background: Although repetitive transcranial magnetic stimulation (rTMS) has been extensively studied in patients with Alzheimer's disease (AD), the clinical evidence remains inconsistent. The purpose of this meta-analysis was to evaluate the effects of rTMS on global cognitive function in patients with AD. Methods: An integrated literature search using 4 databases (PubMed, Web of Science, Embase, and Cochrane Library) was performed to identify English language articles published up to October 6, 2021. We pooled Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) scores using a random-effects model via RevMan 5.4 software. We calculated estimates of mean differences (MD) with 95% confidence intervals (CI). The primary outcomes were pre-post treatment changes in global cognition as measured using MMSE and ADAS-Cog immediately after rTMS treatment, and the secondary outcome was duration of cognitive improvement (1-1.5 and ≥3 months). Results: Nine studies with 361 patients were included in this meta-analysis. The results showed that rTMS significantly improved global cognitive function immediately following rTMS treatment [(MD) 1.82, 95% confidence interval (CI) 1.41-2.22, p < 0.00001, MMSE; 2.72, 95% CI, 1.77-3.67, p < 0.00001, ADAS-Cog], and the therapeutic effects persisted for an extended duration (2.20, 95% CI, 0.93-3.47, p =0.0007, MMSE; 1.96, 95% CI, 0.96-2.95, p = 0.0001, ADAS-Cog). Subgroup analyses showed that high frequency rTMS targeted to the left dorsolateral prefrontal cortex (DLPFC) for over 20 sessions induced the greatest cognitive improvement, with effects lasting for more than 1 month after the final treatment. There were no significant differences in dropout rate (p > 0.05) or adverse effect rate (p > 0.05) between the rTMS and control groups. Conclusions: Repetitive TMS is a potentially effective treatment for cognitive impairment in AD that is safe and can induce long-lasting effects. Our results also showed that ADAS-cog and MMSE differed in determination of global cognitive impairment. Systematic review registration: http://www.crd.york.ac.uk/PROSPERO, PROSPERO CRD42022315545.

High-frequency repetitive transcranial magnetic stimulation improves spatial episodic learning and memory performance by regulating brain plasticity in healthy rats.

Background: Repetitive transcranial magnetic stimulation (rTMS) is an effective way to stimulate changes in structural and functional plasticity, which is a part of learning and memory. However, to our knowledge, rTMS-induced specific activity and neural plasticity in different brain regions that affect cognition are not fully understood; nor are its mechanisms. Therefore, we aimed to investigate rTMS-induced cognition-related neural plasticity changes and their mechanisms in different brain regions. Methods: A total of 30 healthy adult rats were randomly divided into the control group and the rTMS group (n = 15 rats per group). The rats in the control and the rTMS group received either 4 weeks of sham or high-frequency rTMS (HF-rTMS) over the prefrontal cortex (PFC). Cognitive function was detected by Morris water maze. Functional imaging was acquired by resting-state functional magnetic resonance imaging (rs-fMRI) before and after rTMS. The protein expressions of BDNF, TrkB, p-Akt, Akt, NR1, NR2A, and NR2B in the PFC, hippocampus, and primary motor cortex (M1) were detected by Western blot following rTMS. Results: After 4 weeks of rTMS, the cognitive ability of healthy rats who underwent rTMS showed a small but significant behavioral improvement in spatial episodic learning and memory performance. Compared with the pre-rTMS or the control group, rats in the rTMS group showed increased regional homogeneity (ReHo) in multiple brain regions in the interoceptive/default mode network (DMN) and cortico-striatal-thalamic network, specifically the bilateral PFC, bilateral hippocampus, and the left M1. Western blot analyses showed that rTMS led to a significant increase in the expressions of N-methyl-D-aspartic acid (NMDA) receptors, including NR1, NR2A, and NR2B in the PFC, hippocampus, and M1, as well as an upregulation of BDNF, TrkB, and p-Akt in these three brain regions. In addition, the expression of NR1 in these three brain regions correlated with rTMS-induced cognitive improvement. Conclusion: Overall, these data suggested that HF-rTMS can enhance cognitive performance through modulation of NMDA receptor-dependent brain plasticity.

High-frequency repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex may reduce impulsivity in patients with methamphetamine use disorders: A pilot study.

Background: Individuals who use methamphetamine (MA) for a long period of time may experience decreased inhibition and increased impulsivity. In order to reduce impulsivity or improve inhibitory control ability, high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has attracted much attention of researchers. Recent studies on addiction have shown that rTMS can stimulate different brain regions to produce different therapeutic effects. Recent work also suggests that HF-rTMS over right dorsolateral prefrontal cortex (DLPFC) does not affect the impulsivity of patients with alcohol use disorder; while HF-rTMS over left DLPFC could improve the impulsivity of patients with alcohol use disorder and cigarette smokers. However, it should be noted that empirical studies applying HF-rTMS over left DLPFC of patients with MA use disorders (MAUD) (to evaluate its effect on impulsivity) are still lacking. Methods: Twenty-nine patients with MAUD underwent five sessions of HF-rTMS on the left DLPFC per week for 4 consecutive weeks. The cue-induced craving and stop-signal and NoGo task were assessed pre-rTMS and post-rTMS (at the end of the 4-week rTMS treatment). In addition, 29 healthy controls were recruited. There was no rTMS intervention for the controls, the performance of the stop-signal and NoGo task was evaluated on them. Results: In total, HF-rTMS of the left DLPFC significantly decreased MA-dependent patients' cue-induced craving and stop-signal reaction time (SSRT). For SSRT, the pre-test of experimental group was significantly higher than the score of control group. In the experimental group, the pre-test score was significantly higher than the post-test score. For Go and stop-signal delay (SSD), the pre-test scores of the experimental group was significantly lower than the scores of the control group. No significant difference was found between the pre-test and the post-test scores of the experimental group. Conclusion: Add-on HF-rTMS of left DLPFC may be an effective intervention for reducing impulsivity and cue-induced craving of patients with MAUD. Future research with a control group of MAUD that does not undergo the treatment is needed to confirm the effectiveness.

USP18 contributes to the proliferation and migration of ovarian cancer cells by regulating the AKT/mTOR signaling pathway.

Ubiquitin-specific peptidase (USP)18 is elevated in tumor tissues and is associated with tumor malignancy. USP18 functions as an oncogene in different cancers. However, the role of USP18 in ovarian cancer was poorly understood. TCGA database showed that USP18 was elevated in ovarian cancer tissues. Additionally, USP18 mRNA and protein expression was also up-regulated in tumor tissues. The functional assays were then designed via siRNA-mediated knockdown of USP18. The results showed that knockdown of USP18 reduced cell viability and ovarian cancer proliferation. Furthermore, cell apoptosis was promoted by USP18 silencing, and interference of USP18 suppressed cell migration and invasion. The expression of phosphorylated AKT (p-AKT) and p-mTOR protein was decreased in ovarian cancer cells by USP18 knockdown. Inhibition of AKT attenuated the decrease in cell apoptosis induced by USP18 overexpression and increased cell viability and migration. In conclusion, USP18 promoted the proliferation and migration of ovarian cancer cells by activating AKT/mTOR signaling.

Effectiveness of a Novel Contralaterally Controlled Neuromuscular Electrical Stimulation for Restoring Lower Limb Motor Performance and Activities of Daily Living in Stroke Survivors: A Randomized Controlled Trial.

Background: Contralaterally controlled neuromuscular electrical stimulation (CCNMES) is a novel electrical stimulation treatment for stroke; however, reports on the efficacy of CCNMES on lower extremity function after stroke are scarce. Objective: To compare the effects of CCNMES versus NMES on lower extremity function and activities of daily living (ADL) in subacute stroke patients. Methods: Forty-four patients with a history of subacute stroke were randomly assigned to a CCNMES group and a NMES group (n = 22 per group). Twenty-one patients in each group completed the study per protocol, with one subject lost in follow-up in each group. The CCNMES group received CCNMES to the tibialis anterior (TA) and the peroneus longus and brevis muscles to induce ankle dorsiflexion motion, whereas the NMES group received NMES. The stimulus current was a biphasic waveform with a pulse duration of 200 µs and a frequency of 60 Hz. Patients in both groups underwent five 15 min sessions of electrical stimulation per week for three weeks. Indicators of motor function and ADL were measured pre- and posttreatment, including the Fugl-Meyer assessment of the lower extremity (FMA-LE) and modified Barthel index (MBI). Surface electromyography (sEMG) assessments included average electromyography (aEMG), integrated electromyography (iEMG), and root mean square (RMS) of the paretic TA muscle. Results: Values for the FMA-LE, MBI, aEMG, iEMG, and RMS of the affected TA muscle were significantly increased in both groups after treatment (p < 0.01). Patients in the CCNMES group showed significant improvements in all the measurements compared with the NMES group after treatment. Within-group differences in all post- and pretreatment indicators were significantly greater in the CCNMES group than in the NMES group (p < 0.05). Conclusion: CCNMES improved motor function and ADL ability to a greater extent than the conventional NMES in subacute stroke patients.

Psychometric investigation of the Chinese version of the Habit, Reward and Fear Scale (HRFS).

BACKGROUND: Tobacco use is one of the most important risk factors for health, and China is the largest producer and consumer of tobacco in the world. Monitoring and controlling the tobacco epidemic is an important issue. However, the motivation underlying smoking behavior is complex and specific to the individual. The Habit, Reward and Fear Scale (HRFS) is a feasible tool to evaluate this complex motivation. OBJECTIVES: To validate the psychometric properties of the HRFS Chinese version (HRFS-C) and to assess the relationship between motivation and smoking behavior. METHOD: We recruited 967 participants through social media and assessed their smoking behavior with three instruments: the Fagerstrom Test for Nicotine Dependence-Chinese version (FTND-C), the Questionnaire on Smoking Urges-Brief Scale-Chinese version (QSU-brief-C), and the HRFS-C. Ultimately, we retained 700 valid data points. Cronbach's α and split-half tests were used to evaluate the reliability. Confirmatory factor analysis, Pearson's r and an analysis of variance (ANOVA) were used to evaluate the validity. In addition, linear regression was used to explore the relationship among the three instruments. The HRFS-C showed good homogeneity (α = 0.965), concurrent validity, and discriminant validity. A significant linear relationship was observed among the FTND-C, QSU-brief-C, and HRFS-C (p < .001). CONCLUSION: The motivation measured by the HRFS-C can significantly predict nicotine dependence and craving in the smoking population. The HRFS-C can be used to carry out targeted interventions for addicted patients (e.g., motivational enhancement therapy).

Pictures Library of Smoking Cravings: Development and Verification of Smokers and Non-smokers.

Background: The cue-induced craving by addiction related materials is commonly employed in addiction research; however, no existing standardized picture database based on the expectation model of craving has been developed. We prepared and validated a Pictures Library of Smoking Cravings (PLSC) in this study. Methods: We captured pictures 366 smoking and 406 control pictures (matched in content). We selected 109 smoking pictures and 115 control pictures and asked participants to provide ratings of craving, familiarity, valence, and arousal induced in them. Participants were divided into three groups: non-smokers (n = 211), light smokers (n = 504), and heavy smokers (n = 101). Results: The results showed that smoking pictures evoked a greater craving, familiarity, and arousal than control pictures in smokers (ps < 0.01). In addition, craving caused by smoking pictures was positively associated with the Fagerström test for nicotine dependence score in dependent smokers. Conclusions: Overall, the contemporary results showed that PLSC is effective and can be used in smoking-related studies.

Clinical effects of high-intensity laser therapy on patients with chronic refractory wounds: a randomised controlled trial.

OBJECTIVE: To investigate the effectiveness of high-intensity laser therapy (HILT) on chronic refractory wounds.DesignRandomised controlled trial. SETTING: The outpatient wound care department of the Affiliated Jiangsu Shengze Hospital of Nanjing Medical University from August 2019 to June 2020. PARTICIPANTS: Sixty patients were enrolled in this study and were randomised into control (n=30) and treatment (n=30) groups. INTERVENTIONS AND OUTCOME MEASURES: The control group was treated only with conventional wound dressing, whereas the treatment group received irradiation with HILT in addition to standard wound care, such as debridement, wound irrigation with normal saline solution and application of dressing and sterile gauze. Patient scores on the Bates-Jensen Wound Assessment Tool (BWAT) and Pressure Ulcer Scale for Healing (PUSH) were evaluated before and after 1, 2 and 3 weeks of treatment. RESULTS: One patient was excluded from the control group, and a total of 59 subjects completed the trial. The BWAT scores significantly decreased in the treatment group compared with the control group at the end of 3-week treatment (difference=-3.6; 95% CI -6.3 to-0.8; p<0.01). Similarly, patients in treatment group showed a significant reduction of PUSH scores compared with the control group (difference=-5.3; 95% CI -8.1 to -2.6; p<0.01). CONCLUSIONS: The therapeutic effects of HILT on chronic refractory wounds are significant and far more superior to those of conventional wound dressing. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry; ChiCTR1900023157. URL: http://www.chictr.org.cn/showproj.aspx?proj=38866.

Development of highly efficient platinum catalysts for hydroalkoxylation and hydroamination of unactivated alkenes.

Hydrofunctionalization, the direct addition of an X-H (e.g., X=O, N) bond across an alkene, is a desirable strategy to make heterocycles that are important structural components of naturally occurring molecules. Described here is the design and discovery of "donor-acceptor"-type platinum catalysts that are highly effective in both hydroalkoxylation and hydroamination of unactivated alkenes over a broad range of substrates under mild conditions. A number of alkene substitution patterns are accommodated, including tri-substituted, 1,1-disubstituted, (E)-disubstituted, (Z)-disubstituted and even mono-substituted double bonds. Detailed mechanistic investigations suggest a plausible pathway that includes an unexpected dissociation/re-association of the electron-deficient ligand to form an alkene-bound "donor-acceptor"-type intermediate. These mechanistic studies help understand the origins of the high reactivity exhibited by the catalytic system, and provide a foundation for the rational design of chiral catalysts towards asymmetric hydrofunctionalization reactions.

Evaluation of the short-term efficacy and safety of bevacizumab combined with doxorubicin liposomes in the treatment of patients with platinum-resistant recurrent epithelial ovarian cancer / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨贝伐珠单抗联合多柔比星脂质体治疗铂类耐药复发性卵巢上皮性癌患者的近期疗效和不良反应，并随访生存情况。方法：选取中国人民解放军联勤保障部队第九〇一医院2018年1月至2019年12月收治的76例铂类耐药复发性卵巢上皮性癌患者，采用数字随机分组法分为对照组38例、观察组38例，对照组给予多柔比星脂质体单药化疗4个周期，观察组给予贝伐珠单抗联合多柔比星脂质体化疗4个周期，观察两组患者治疗后近期疗效和不良反应，以及血清肿瘤标志物人附睾蛋白4（human epididymis protein 4，HE4）、糖类抗原125（carbohydrate antigen 125，CA125）变化，并随访总生存期（OS）和无疾病进展生存期（PFS）。结果：对照组患者客观有效率（ORR）为40.54%、疾病控制率（DCR）为67.57%，观察组患者ORR为69.44%、DCR为88.89%，观察组ORR和DCR显著高于对照组（均P<0.05）。治疗后观察组患者血清HE4和CA125分别为（142.67±46.81）pmol/L、（31.79±11.65）U/L，显著低于对照组患者的（219.33±75.67）pmol/L、（57.05±17.85）U/L（均P<0.05）。两组患者的胃肠反应、骨髓抑制、肝肾功能损伤、心脏毒性、过敏反应、血栓栓塞和出血等不良反应相比较差异无统计学意义（均P>0.05）；观察组患者高血压发生率显著高于对照组（P<0.05），但可控、可耐受。观察组患者中位OS 和中位PFS分别分别为17.2个月和10.9个月，显著长于对照组患者的14.1个月和7.8个月（均P<0.05）。结论：对于铂类耐药复发性卵巢上皮性癌患者，贝伐珠单抗联合多柔比星脂质体近期疗效可靠、安全性好、不良反应可耐受，值得临床推广。

Asymmetric Transfer Hydrogenation of Densely Functionalized Diheteroaryl and Diaryl Ketones by a Ru-Catalyst of Minimal Stereogenicity.

A highly enantioselective asymmetric transfer hydrogenation (ATH) of densely functionalized diheteroaryl and diaryl ketones was developed using Ru-catalysts of minimal stereogenicity. Various ketone substrates with structurally and electronically similar groups attached to the prochiral centers were reduced successfully in good to excellent enantioselectivities and yields. This protocol provides practical and efficient access to chiral diheteroarylmethanols and benzhydrols, which are key intermediates in pharmaceuticals and biologically active compounds.

Cajaninstilbene acid analogues as novel quorum sensing and biofilm inhibitors of Pseudomonas aeruginosa.

Biofilm formation and virulence factor secretion in opportunistic pathogen Pseudomonas aeruginosa are essential for establishment of chronic and recurrent infection, which are regulated by quorum sensing (QS) system. In this study, a set of cajaninstilbene acid analogues were designed and synthesized, and their abilities to inhibit QS and biofilm formation were investigated. Among all the compounds, compounds 3g, 3m and 3o showed potent anti-biofilm activity, especially 3o exhibited promising biofilm inhibitory activity with biofilm inhibition ratio of 49.50 ± 1.35% at 50 µM. Three lacZ reporter strains were constructed to identify the effects of compound 3o on different QS systems. Compound 3o showed the suppression on the expression of lasB-lacZ and pqsA-lacZ as well as on the production of their corresponding virulence factors. Therefore, compound 3o is expected to be generated as a lead compound with inhibition of biofilm formation and QS of Pseudomonas aeruginosa.

Synthesis and Biological Evaluation of Cajaninstilbene Acid and Amorfrutins A and B as Inhibitors of the Pseudomonas aeruginosa Quorum Sensing System.

The quorum sensing (QS) system inhibitors of Pseudomonas aeruginosa are thought to attenuate bacterial pathogenicity and drug resistance by inhibiting biofilm formation and the production of virulence factors. In this study, a synthetic approach to the natural products cajaninstilbene acid (1) and amorfrutins A (2) and B (3) has been developed and was characterized by the Heck reaction, which was used to obtain the stilbene core and a Pinick oxidation to give the O-hydroxybenzoic acid. The biological activities of these compounds against the P. aeruginosa quorum sensing systems were evaluated. Amorfrutin B (3) showed promising antibiofilm activity against P. aeruginosa PAO1 with a biofilm inhibition ratio of 50.3 ± 2.7. Three lacZ reporter strains were constructed to identify the effects of compound 3 on different QS systems. Suppression efficacy of compound 3 on the expression of lasB-lacZ and pqsA-lacZ as well as on the production of their corresponding virulence factors elastase and pyocyanin was observed.

4-arylamidobenzyl substituted 5-bromomethylene-2(5H)-furanones for chronic bacterial infection.

Bacterial quorum-sensing (QS) can cause bacterial biofilm formation, thus induce antibiotic resistance and inflammation in chronic bacterial infections. A series of novel 4-arylamidobenzyl substituted 5-bromomethylene-2(5H)-furanones were designed by introducing of brominated furanones into rosiglitazone skeleton, and their potential application in the treatment of chronic bacterial infection was evaluated with regard to their disruption of quorum sensing and anti-inflammatory activities in vitro as well as in animal infection model. Compound 2e displayed both potent QS inhibitory activity and anti-inflammatory activity. Further mechanism studies revealed that the biological effects of 2e and 2k could be attributed, at least in part, to their interaction with PPARγ, and consequent suppression of the activation of NF-κB and MAPK cascades. Importantly, pretreatment with 2e significantly protects mice from lethal-dose LPS challenge. Thus, these data suggest that the dual effective derivative 2e may serve as a valuable candidate for the treatment of chronic bacterial infection.

Novel 4-(4-substituted amidobenzyl)furan-2(5H)-one derivatives as topoisomerase I inhibitors.

In this study, two series of novel 4-(4-substituted amidobenzyl)furan-2(5H)-one derivatives containing an α,ß-unsaturated lactone fragment were synthesized and screened for Topo I inhibition and antitumor activity. The topoisomerase I inhibitory activities and cytotoxicities against three human cancer cell lines (MCF-7,Hela,A549) were evaluated. The results revealed that series 2, compounds bearing an exocyclic double bond on the furanone ring, generally showed more potent activity than series 1, compounds lacking an exocyclic double bond. Several compounds of series 2 possess significant Topo I inhibitory activity and potent antiproliferative activity against cancer cell lines. Further mechanism studies of the most active compound of series 2 (B-15) indicated that synthetic compounds can not only stabilize the drug-enzyme-DNA covalent ternary complex as well as camptothecin, but also interfere with the binding between Topo I and DNA. The binding patterns of these compounds with Topo I and structure-activity relationships are discussed.

Synthesis and antibacterial activities of acylide derivatives bearing an aryl-tetrazolyl chain.

Seventeen acylides bearing an aryl-tetrazolyl alkyl-substituted side chain were synthesized, starting from clarithromycin, via several reactions including hydrolysis, acetylating, esterification, carbamylation, and Michael addition. The structures of all new compounds were confirmed by (1)H nuclear magnetic resonance spectroscopy, (13)C nuclear magnetic resonance spectroscopy, and mass spectrometry. All these synthesized acylides were evaluated for in vitro antimicrobial activities against gram-positive pathogens (Staphylococcus aureus, Staphylococcus epidermidis) and gram-negative pathogens (Pseudomonas aeruginosa, Escherichia coli), using the broth microdilution method. Results showed that compounds 10 e, 10 f, 10 g, 10 h, 10 o have good antibacterial activities.

Seasonal variation of metabolic thermogenesis in Eurasian tree sparrows (Passer montanus) over a latitudinal gradient.

Phenotypic flexibility of various morphological and physiological characters is widespread in animals. Resident endothermic animals of temperate climates provide a natural experiment in phenotypic flexibility. In this study, we took an integrative approach to assess seasonal and geographic influences on metabolism in Eurasian tree sparrows (Passer montanus). We measured resting metabolic rate (RMR), masses of internal organs, mitochondrial respiration capacities in liver and muscle, cytochrome C oxidase (COX) activities in liver and muscle, and circulating levels of plasma triiodothyronine (T3) and thyroxine (T4) in summer and winter sparrows at two sites from southeastern (Wenzhou) and northeastern (Qiqihar) China that differ in climate. Body masses of tree sparrows were significantly higher in winter than in summer at both sites but did not differ with latitude. RMRs of tree sparrows varied significantly with both latitude and season, with RMRs of Qiqihar birds being higher than those of Wenzhou birds and with RMRs being higher in winter than in summer. Consistently, dry masses of brain, lung, liver, gizzard, small intestine, rectum, and total digestive tract varied significantly with either latitude or season. State 4 respiration and COX activity in liver and muscle were remarkably higher in Qiqihar and increased significantly in winter. Circulating levels of plasma T3 also showed significant seasonal and latitudinal variation and was higher in Qiqihar in winter than in other groups. These data suggest that tree sparrows mainly coped with cold by enhancing thermogenic capacities through heightened activity of respiratory enzymes and higher levels of plasma thyroid hormones (T3). These results are consistent with a pronounced seasonal and latitudinal phenotypic flexibility mediated through physiological and biochemical adjustments in Eurasian tree sparrows.

3D-QSAR and molecular docking for the discovery of ketolide derivatives.

INTRODUCTION: There is an urgent need to discover novel antibiotics to overcome the growing problem of antibiotic resistance, which has become a serious concern in current medicine. Ketolides, the third generation of macrolide antibiotics, have shown promising effect against macrolide-resistant pathogens in respiratory diseases. Currently, a number of ketolide derivatives with excellent antibacterial activities have been reported, while their structure-activity relationships (SARs) were rarely explored systematically. Computer-aided drug design (CADD) such as 3D-QSAR and molecular docking are useful tools to study drug SARs in medicinal chemistry. Using these technologies, ketolide derivatives were systemically analyzed revealing important useful information about their SARs, providing useful information which can guide new drug design and optimization. AREAS COVERED: The authors provide an overview of the currently reported 3D-QSAR models of ketolide derivatives. The authors present a comprehensive SAR model obtained from in-depth 3D-QSAR and molecular docking analysis for all kinds of ketolide derivatives. EXPERT OPINION: 3D-QSAR has been shown to be a reliable tool that had successfully assisted the design of several new antibiotics with improved activity and reduced toxicity. By applying 3D-QSAR and molecular docking, a comprehensive and systematic SAR model for ketolide derivative discovery was formed, which is important to guide future drug design for the discovery of better ketolides with lower toxicity.

Geographic variation in basal thermogenesis in little buntings: relationship to cellular thermogenesis and thyroid hormone concentrations.

Acclimatization to different ambient conditions is an essential prerequisite for survival of small passerine birds. Long-distance migration and winter acclimatization induce similar physiological and biochemical adjustments in passerines. To understand metabolic adaptations, the resting metabolic rate (RMR), the thermogenic properties of mitochondria in liver and muscle, and the activity of thyroid hormones were examined in field-captured little buntings (Emberiza pusilla) between Southeastern (Wenzhou) and Northeastern (Qiqihar) China from March to May in 2008 during their migration. Twelve birds were trapped from March to April in Wenzhou region, Zhejiang Province (27°29'N, 120°51'E) and eleven birds originated from April to May in Qiqihar region, Heilongjiang Province (47°29'N, 124°02'E). We found that RMRs of little buntings were significantly higher in Qiqihar than in Wenzhou. Consistently, mitochondrial state-4 respiration capacities and cytochrome c oxidase activities (COX) in liver and muscle, and circulating levels of plasma triiodothyronine (T(3)) of little buntings were also significantly higher in Qiqihar than in Wenzhou. Variation in metabolic biochemical markers of liver and muscle, such as state-4 respiration and COX, and variation in thyroid hormone levels were correlated with variation in RMR. There was also a positive relationship between T(3) and metabolic biochemical markers. Little buntings mainly coped with a cold environment by enhancing thermogenic capacities through enhanced respiratory enzyme activities and plasma T(3). These results support the view that the primary means by which small birds meet energetic challenges of cold conditions is through metabolic adjustments.