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Breast cancer is one of the most common cancers. Even if breast cancer patients initially respond to treatment, developed resistance can lead to a poor prognosis. Cancer stem cells (CSCs) are a group of undifferentiated cells with self-renewal and multipotent differentiation characteristics. Existing evidence has shown that CSCs are one of the determinants that contribute to the heterogeneity of primary tumors. The emergence of CSCs causes tumor recurrence, metastasis, and therapeutic resistance. Previous studies indicated that different stemness-associated surface markers can identify other breast cancer stem cell (BCSC) subpopulations. Deciphering the critical signaling networks that are involved in the induction and maintenance of stemness is essential to develop novel BCSC-targeting strategies. In this review, we reviewed the biomarkers of BCSCs, critical regulators of BCSCs, and the signaling networks that regulate the stemness of BCSCs. [ABSTRACT FROM AUTHOR]

Ice storage sphere systems are favored in the field of energy storage, however, the poor thermal conductivity of phase change materials (PCM) seriously weakens their wide application. Metal foam has been shown to enhance its heat transfer. In this paper, we investigate the impact of varying the filling radius ratio of foam metal to further improve energy storage performance and reduce costs in ice storage spheres. Computational fluid dynamics are employed to analyze the heat transfer and solidification processes. The enthalpy-porosity method is used to describe PCM solidification, while the local equilibrium thermal (LET) model characterizes heat transfer between the PCM and foam metal. The study explores temperature field variations, solid phase fraction changes, solidification times, and cold storage volumes, accounting for natural convection. By comparing solidification rates and other relevant parameters, the effect of foam metal filling on the solidification process is explored. Moreover, a new evaluation index is proposed, which can assess the overall performance of ice storage systems in real-time, considering market prices. The results show that natural convection is the primary heat transfer mode in pure PCM-ffild ice storage spheres, whereas smaller foam metal filling radii significantly inhibit natural convection, resulting in heat conduction as the dominant mode. Without specific requirements, an optimal fill radius ratio of 9/13 is determined. This paper offers a comprehensive understanding of cold storage employing various foam metal filling radios, contributing to advancements in efficient thermal energy storage systems. [ABSTRACT FROM AUTHOR]

Based on the crystallographic studies of diarylpyrimidines (DAPYs), we embarked on incorporating the hydrophilic piperidyl or morpholinyl group into the known DAPY derivatives bearing the pyridine moiety as a core structure, with the double aim to exploit additional interactions with the HIV-1 NNRTI binding pocket (NNIBP), as well as to improve the compound solubility. The antiviral evaluation result show that the most potent compounds I-8b2 , I-8b3 , I-8b4 and I-8c3 exhibited anti-HIV-1 (III B ) strain activity ranging from 7.4 nM to 9.4 nM (SI = 168–1283), superior to FDA-approved drugs of nevirapine (NVP), lamivudine (3TC) and delavirdine (DLV), and comparable to etravirine (ETV), zidovudine (AZT) and efavirenz (EFV). Additionally, compounds I-8c2 and I-8c3 showed moderate activity against NNRTI resistant strains baring mutations K103N and Y181C with EC 50 values of 6.2 μM and 6.8 μM, respectively. Preliminary structure-activity relationships (SARs), reverse transcriptase inhibition efficacy and molecular modeling of selected compounds are also presented. These outcomes support our design hypothesis and demonstrate that the piperidyl group modified pyridine-typed DAPY derivatives are highly potent NNRTIs with improved water solubility. [ABSTRACT FROM AUTHOR]

The development of novel NNRTIs with activity against variants of HIV-1RT is crucial for overcoming treatment failure. In the present study, a series of novel 6-substituted diarylpyridine derivatives targeting the entrance channel of the NNIBP of RT were designed through a molecular hybridization strategy. Encouragingly, these new diarylpyridine derivatives were found to be active against wild-type (WT) HIV-1 with an EC50 values ranging from 0.035 μM to 1.99 μM. Nearly half of them exhibited more potent inhibitory activities in cellular assays than the control drug nevirapine (NVP). Notably, three most promising compounds If (EC50 = 35 nM), Ia (EC50 = 43 nM) and IIa (EC50 = 41 nM) showed high potency against WT and were comparable to the reference drug delavirdine (DLV) (EC50 = 33 nM). Moreover, compounds Ib , IIb and IIh displayed effective activity against the most common clinically observed single and double-mutated HIV-1 strains in micromolar concentrations. In particular, the inhibition of IIb against the K103N mutation (EC50 = 49 nM), which confers resistance to a wide variety of NNRTIs, was about 140 times more effective than NVP (EC50 = 6.78 μM), 50 times more than DLV (EC50 = 2.48 μM) and about 3 times more than EFV (EC50 = 0.12 μM), indicating that the newly designed compounds have great potential to be further developed as new anti-HIV-1 agents. Preliminary structure-activity relationships (SARs) and molecular modeling of the new diarylpyridine derivatives were discussed in detail. [ABSTRACT FROM AUTHOR]

Through a structure-based molecular hybridization approach, a novel series of diarylnicotinamide derivatives (DANAs) targeting the entrance channel of HIV-1 NNRTIs binding pocket (NNIBP) were rationally designed, synthesized and evaluated for their anti-HIV activities in MT-4 cells together with the inhibition against the reverse transcriptase (RT) in an enzymatic assay. Encouragingly, most of the new DANAs were found to be active against wild-type HIV-1 with an EC 50 in the range of 0.027–4.54 μM. Among them, compound 6b11 (EC 50 = 0.027 μM, SI > 12518) and 6b5 (EC 50 = 0.029 μM, SI = 2471) were identified as the most potent inhibitors, which were more potent than the reference drugs nevirapine (EC 50 = 0.31 μM) and delavirdine (EC 50 = 0.66 μM). Some DANAs were also active at micromolar concentrations against the K103N + Y181C resistant mutant. Compound 6b11 exhibited the highest enzymatic inhibition activity (IC 50 = 20 nM), which is equal to that of efavirenz (EC 50 = 20 nM) and 31 times higher than that of nevirapine (EC 50 = 0.62 μM). Preliminary structure-activity relationships (SARs) and molecular modeling of these new DANAs have been discussed. [ABSTRACT FROM AUTHOR]

A series of 4-(naphthalen-1-yl)-1,2,5-thiadiazol-3-hydroxyl derivatives ( Ia- Im and II a- II e) designed as novel HIV-1 non-nucleoside reverse transcriptase inhibitors ( NNRTIs) was synthesized via an expeditious route and evaluated for their anti- HIV activities in MT-4 cell cultures. All the synthesized compounds were structurally confirmed by spectral analyses. Biological results showed that three analogues displayed moderate inhibitory activity against wild-type (wt) HIV-1 replication with EC50 values ranging from 16 to 22 μ m. Molecular docking of compound Ih with wt HIV-1 RT was performed to understand the binding mode between these inhibitors and the wt HIV-1 RT and to rationalize some SARs. [ABSTRACT FROM AUTHOR]

Abstract: Guided by crystal structures of HIV-1 RT/DAPY complex and molecular modeling studies, a series of novel DAPY derivatives were rationally designed, synthesized and evaluated for their anti-HIV activities. Among them, 16 compounds significantly inhibited HIV-1 IIIB replication with EC50 values lower than 66 nM. Particularly, compound 7a was the most potent inhibitor against HIV-1 wild-type and double RT mutant HIV-1 strain K103N/Y181C, with an EC50 value of 2.5 nM (SI = 13,740) and 0.33 μM (SI = 107), respectively. Unexpectedly, compound 8c was found to show moderate anti-HIV-2 potency (EC50 = 5.57 μM). Preliminary structure–activity relationships (SARs) and molecular modeling of these new analogues were also discussed in detail. [Copyright &y& Elsevier]

Abstract: Based on crystallographic overlays of the known inhibitors TMC125 and R221239 complexed in RT, we designed a novel series of 4-phenoxy-6-(phenylamino)pyridin-2(1H)-one derivatives as HIV NNRTIs by molecular hybridization approach. The biological testing results indicated that 2-pyridone scaffold of these inhibitors was indispensable for their anti-HIV-1 activity, and substitution of halogen at the 3-position of the 2-pyridone ring would decrease the anti-HIV activity. Four most potent compounds had anti-HIV-1 IIIB activities at low micromolar concentrations (EC50 =0.15–0.84μM), comparable to that of nevirapine and delavidine. Some compounds were selected to test their anti-HIV-1 RT inhibitory action and to perform molecular modeling studies to predict the binding mode of these 2-pyridone derivatives. [Copyright &y& Elsevier]

Abstract: A novel series of 3-benzyloxy-linked pyrimidinylphenylamine derivatives (8a–8s) was designed, synthesized and evaluated for their in vitro anti-HIV activity in MT-4 cell cultures. Most of the compounds inhibited wild-type (wt) HIV-1 replication in the lower micromolar concentration range (EC50 =0.05–35μM) with high selectivity index (SI) values (ranged from 10 to >4870). In particular, 8h and 8g displayed excellent antiretroviral activity against wt HIV-1 with low cytotoxicity (EC50 =0.07μM, CC50 >347μM, SI >4870; EC50 =0.05μM, CC50 =42μM, SI=777, respectively), comparable to that of the marked drug nevirapine (EC50 =0.113μM, CC50 >15μM, SI >133). In order to confirm the binding target, 8h was selected to perform the anti-HIV-1 RT assay. Additionally, preliminary structure activity relationship (SAR) analysis and molecular docking studies of newly synthesized compounds were also discussed, as well as the predicted physicochemical properties. [Copyright &y& Elsevier]

Abstract: A series of N 2,N 4-disubstituted-1,1,3-trioxo-2H,4H-pyrrolo[1,2-b][1,2,4,6]thiatriazine derivatives (PTTDs) was designed and synthesized by a facile route. The biological assay results showed that five most potent compounds displayed inhibitory activity against HIV-1 at low micromolar concentrations (EC50 =5.1–8.9μM). Structure–activity relationship analysis indicated that N 2-(3-halogenated-benzyl) analogues were more potent than N 2-(unsubstituted-benzyl) analogues. The N 4-substitutions contributed to the antiviral activity in the following order: 2-/3-cyano substituted benzyl > 2-/3-halogenated benzyl > non-substituted benzyl > 4-halogenated benzyl. Docking studies of the representative compound revealed the binding conformation of these compounds and provided critical insights for the further development of PTTD analogues. [Copyright &y& Elsevier]

ABSTRACT We reported a facile and efficient methodology to synthesize derivatives of pyrrolo[1,2-b][1,2,4,6]thiatriazine (PTTD): a new bridgehead nitrogen heterocyclic system. Treatment of methyl pyrrole-2-carboxylate with N-benzylsulfamoyl chlorides followed by subsequent hydrolysis reaction afforded 1-benzylsulfamoyl-1H-pyrrole-2-carboxylic acids, which underwent ring-closing reaction by treatment with diphenyl phosphorazidate via Curtius rearrangement; subsequent alkylation reaction afforded the desired 2,4-disubstituted-1,1,3-trioxo-2H,4H-PTTDs. [ABSTRACT FROM AUTHOR]

Abstract: The present work is an extension of our ongoing efforts towards the development and identification of new molecules with anti-HIV activity which have previously led to the discovery of arylazolylthioacetanilides as highly active NNRTIs. In this article, a series of 2-2-(3-(2-chlorophenyl)pyrazin-2-ylthio)-N-arylacetamide derivatives were synthesized and evaluated for in vitro anti-HIV activity. Most of the tested compounds exhibited moderate activities against wild-type HIV-1. Among them, compound 6k showed significant activity against wild-type HIV-1 with an EC50 value of 1.7μM, along with moderate activity against wild-type reverse transcriptase (RT). The preliminary structure–activity relationship (SAR) and docking calculations of this new series of compounds were also investigated, which may help designing more potent molecules. [Copyright &y& Elsevier]

The C-X-C motif ligand 8 and C-X-C chemokine receptor 2 (CXCL8-CXCR2) axis is involved in pathogenesis of various diseases including inflammation and cancers. Various CXCR2 antagonists are under development for several diseases. Our previous high-throughput cell-based assay specific for CXCR2 has identified a pyrimidine-based compound CX797 acting on CXCR2 down-stream signaling. A lead optimization campaign through scaffold-hopping strategy led to a series of 2- t hio u reido t hio p hene-3-carboxylates (TUTP) as novel CXCR2 antagonists. Structure-activity relationship study of TUTPs led to the identification of compound 52 that significantly inhibited CXCR2-mediated β-arrestin recruitment signaling (IC 50 = 1.1 ± 0.01 μM) with negligible effect on CXCL8-mediated cAMP signaling and calcium flux. Similar to the known CXCR2 antagonist SB265610, compound 52 inhibited CXCL8-CXCR2 induced phosphorylation of ERK1/2. TUTP compounds also inhibited CXCL8-mediated cell migration and showed synergy with doxorubicin in ovarian cancer cells, thereby supporting TUTPs as promising compounds for cancer treatment. Image 1 • TUTP compounds were identified as novel CXCR2 antagonists through scaffold-hopping strategy. • TUTP compounds are selective for CXCR2 among over 50 other GPCRs. • TUTP compounds inhibited CXCL8-mediated β-arrestin recruitment and the phosphorylation of ERK1/2. • Combination of TUTP compounds with doxorubicin showed synergistic cytotoxicity in human SKOV3 ovarian cancer cells. [ABSTRACT FROM AUTHOR]

Brequinar, a potent dihydroorotate dehydrogenase (DHODH) inhibitor, has been evaluated in multiple clinical trials as a potential treatment for cancer. To further understand brequinar-based DHODH inhibition and DHODH′s therapeutic relevance in cancer, we have developed novel brequinar-based probes. We disclose a 16-step convergent synthesis of the first brequinar-PROTAC and a four-step approach towards the first mitochondrial-directed brequinar probe. A PROTAC and mitochondria-directed probe of brequinar both possess cytotoxicity that is superior to brequinar in a colony formation assay. [ABSTRACT FROM AUTHOR]

Ring closure and Claisen rearrangement of pyrrole carboxylic acid (III) promoted by diphenylphosphoryl azide leads to the new heterocyclic system (IV) which are further functionalized. [ABSTRACT FROM AUTHOR]

Accurate prenatal diagnosis of congenital duodenal obstruction (CDO) is challenging. We aimed to determine new ultrasound metrics for accurate prenatal diagnosis of fetal CDO. Data pertaining to 46 fetuses with suspected small intestinal obstruction (26 CDO; 16 high jejunal obstructions) were retrospectively analyzed. Prenatal ultrasonographic features including dilated intestinal length, stomach length, maximum intestinal dilatation, ratio of dilated intestinal length at late gestation and dilated stomach length (I/S ratio), and location of distal end of dilated bowel segment relative to spine were compared between CDO and high jejunal obstruction groups. The diagnostic performance of ultrasound indices was evaluated using receiver operating characteristics curve analysis. In 25 out of 26 CDO cases, the distal end of the dilated small intestine segment was located on the right side of spine, while that in the high jejunal obstruction group was located on the left side of spine. The dilated intestinal length and I/S ratio in CDO group were significantly smaller than those in high jejunal obstruction group (p <.05). Dilated intestinal length <51 mm or I/S ratio <1 showed high sensitivity (100, 100%) and specificity (96.1, 92.3%) for CDO (area under the curve: 0.995 and 0.988, respectively). There were no significant differences in the AUCs of dilated intestinal length and I/S ratio. Significant correlation of the site of obstruction in CDO with fetal dilated intestinal length and I/S ratio (r = 0.686; 0.660, p <.001, respectively) were noted. Location of the distal end of the dilated small intestine segment relative to the spine, dilated intestinal length, and I/S ratio may help differentiate fetal CDO from high jejunal obstruction. The latter two metrics were associated with the site of obstruction in CDO patients. [ABSTRACT FROM AUTHOR]

Objective: To systematically evaluate the effect of enhanced recovery after surgery (ERAS) on perioperative nursing of patients undergoing cardiac surgery. Methods: A systematic literature search was performed in PubMed, Embase, Web of science, Cochrane, CNKI, Wanfang, and VIP using predefined search strings from inception of database to May 2021. Randomized control trials (RCTs) with sample size >40 on cardiac surgery with either ERAS nursing or routine nursing reporting extubation (trachea) time, length of stay, out of bed activity time, and nursing satisfaction were included in the analysis. Stata SE 12.0 software was used for statistical analysis. Results: A total of 27 RCTs were included. All the included studies were Chinese due to lack of studies in English. The results of meta‐analysis showed that the extubation time standardized mean difference ([SMD] = −3.11; 95% confidence interval [CI]: −3.77, −2.45; p <.001), out of bed activity time (SMD = −2.89; 95% CI: −3.34, −2.44; p <.001), and hospitalization time (SMD = −2.08; 95% CI: −2.37, −1.79; p <.001) of cardiac surgery patients with ERAS nursing was significantly shorter than those with routine nursing. The patient's satisfaction after surgery with ERAS was higher than that of routine nursing relative risk ([RR] = 1.24; 95% CI: 1.18, 1.30; p <.001). Conclusion: ERAS nursing can accelerate perioperative rehabilitation of patients undergoing cardiac surgery and highly accepted by patients. [ABSTRACT FROM AUTHOR]

Atmospheric dustfall samples from the libraries and dormitories of 14 universities in Wuhan, China, were collected and analyzed for 16 priority polycyclic aromatic hydrocarbons (PAHs). The results showed that the levels of Σ16PAHs in the dustfall from libraries varied from 2.45 to 13.4 μg·g−1, with an average value of 5.06 μg·g−1, while that of dormitories ranged from 2.61 to 10.6 μg·g−1, with an average of 5.19 μg·g−1. The compositions of PAHs in library and dormitory dustfall were similar, and they were dominated by high molecular weight PAHs (HMW-PAHs) (including fluoranthene, benzo(b)fluoranthene, and chrysene), which accounted for 79.2% of the total PAHs. Spatially, the higher levels of PAHs contamination were mainly distributed in areas with high population density and heavy traffic, which suggests that anthropogenic activities made an important contribution to the PAHs emissions. The diagnostic ratios and principal component analyses (PCA) indicated that combustion-related anthropogenic sources, such as petroleum, coal, and biomass combustion, as well as vehicular traffic emission, were the main sources of PAHs bound to dustfall. The toxic equivalent concentrations (BaPeq) of dustfall-bound PAHs ranged from 271 to 2510 μg·kg−1. According to the health risk assessment results, dermal contact was the predominant exposure pathway, followed by ingestion and inhalation. The incremental lifetime cancer risks (ILCRs) of exposure to PAHs in dustfall was 1.230 × 10−6−1.140 × 10−5, which indicates that there are low potential carcinogenic risks in the universities. [ABSTRACT FROM AUTHOR]

After the initial androgen deprivation therapy (ADT), part of the prostate cancer may continuously deteriorate into castration-resistant prostate cancer (CRPC). The majority of patients suffer from the localized illness at primary diagnosis that could rapidly assault other organs. This disease stage is referred as metastatic castration-resistant prostate cancer (mCRPC). Surgery and radiation are still the treatment of CRPC, but have some adverse effects such as urinary symptoms and sexual dysfunction. Hormonal castration therapy interfering androgen receptor (AR) signaling pathway is indispensable for most advanced prostate cancer patients, and the first- and second-generation of novel AR inhibitors could effectively cure hormone sensitive prostate cancer (HSPC). However, the resistance to these chemical agents is inevitable, so many of patients may experience relapses. The resistance to AR inhibitor mainly involves AR mutation, splice variant formation and amplification, which indicates the important role in CRPC. Proteolysis-targeting chimera (PROTAC), a potent technique to degrade targeted protein, has recently undergone extensive development as a biological tool and therapeutic drug. This technique has the potential to become the next generation of antitumor therapeutics as it could overcome the shortcomings of conventional small molecule inhibitors. In this review, we summarize the molecular mechanisms on PROTACs targeting AR signaling for CRPC, hoping to provide insights into drug development and clinical medication. [Display omitted] [ABSTRACT FROM AUTHOR]

In our arduous efforts to develop new potent HIV-1 non-nucleoside reverse transcriptase (RT) inhibitors (NNRTIs), novel piperidine-linked [1,2,4]triazolo[1,5- a ]pyrimidine derivatives were designed, synthesized and evaluated for their antiviral activities in MT-4 cell cultures. Biological results showed that all of the title compounds displayed moderate to excellent activities against wild-type (wt) HIV-1 strain (III B ) with EC 50 values ranging from 8.1 nM to 2284 nM in a cell-based assay. Among them, the most promising analog 7d possessed an EC 50 value of 8.1 nM against wt HIV-1, which was much more potent than the reference drugs DDI, 3 TC, NVP and DLV. Additionally, 7d demonstrated weak activity against the double mutant HIV-1 strain (K103N + Y181C), and was more efficient than NVP in a RT inhibition assay. Besides, some measured and calculated physicochemical properties of 7d , like log P and water solubility, as well as the structure–activity relationships (SARs) analysis have been discussed in detail. Furthermore, the binding mode of the active compound 7d was rationalized by molecular simulation studies. [ABSTRACT FROM AUTHOR]

Guided by crystal structures of HIV-1 RT/DAPY complex and molecular modeling studies, a series of novel [1,2,4]triazolo[1,5-a]pyrimidine derivatives were rationally designed via structure-based core refining approach, synthesized through the readily accessible synthetic methods and evaluated for their anti-HIV activities in MT-4 cells. Preliminary biological evaluation indicated that most of the compounds exhibited marked inhibitory activity against the wild-type HIV-1 III B . Particularly, compound 7n was the most potent inhibitor against wild-type and K103N/Y181C double resistant mutant strain of HIV-1, possessing EC 50 values of 0.02 μM and 7.6 μM, respectively, which were much better than or similar to nevirapine (NVP, EC 50 = 0.15 μM, 2.9 μM) and delavirdine (DLV, EC 50 = 0.07 μM, >36 μM). Besides, some other compounds, 5b , 7c , 7e , 7f , and 7m , were also endowed with favorable anti-HIV-1 potency (EC 50 = 0.07, 0.05, 0.05, 0.07, and 0.05 μM, respectively), which were better than or similar to those of NVP and DLV, suggesting a high potential to further develop this type of bridgehead nitrogen heterocycle as a novel class of NNRTIs with improved antiviral efficacy and resistance profile. The selected compound, 7i , was found moderately inhibitory towards RT (IC 50 = 0.39 μM), which was higher than for ETV (IC 50 = 0.56 μM). Preliminary structure–activity relationships (SARs) and molecular modeling of these new analogues were detailed in this manuscript. [ABSTRACT FROM AUTHOR]

A series of novel pyrimidinylthioacetanilides were designed, synthesized, and evaluated for their biological activity as potent HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). Most of the tested compounds were proved to be effective in inhibiting HIV-1 (IIIB) replication with EC50 ranging from 0.15 μM to 24.2 μM, thereinto compound 15 was the most active lead with favorable inhibitory activity against HIV-1 (IIIB) (EC50 = 0.15 μM, SI = 684). Besides, compound 6 displayed moderate inhibition against the double-mutated HIV-1 strain (K103N/Y181C) (EC50 = 3.9 μM). Preliminary structure–activity relationships (SARs), structure–cytotoxicity relationships (SCRs) data, and molecular modeling studies were discussed as well, which may provide valuable insights for further optimizations. [ABSTRACT FROM AUTHOR]

Objective. To explore the role of Chinese prescriptions in non-small cell lung cancer (NSCLC) and provide references for the application of herbs and prescriptions. Methods. Randomized and quasirandomized controlled clinical trials on Chinese herbal medicine in the treatment of NSCLC were collected from seven databases to establish a database of prescriptions on NSCLC. Data-mining analyses were performed by RStudio (v4.0.3) software. Results. A total of 970 prescriptions were obtained from 945 included studies, involving 7 syndromes and 428 herbs. The main patterns of NSCLC included qi deficiency pattern, yin deficiency pattern, blood deficiency pattern, kidney deficiency pattern, heat toxin pattern, phlegm-dampness pattern, and blood stasis pattern. High-frequency herbs on NSCLC were Astragali Radix (Huangqi), Atractylodis Macrocephalae Rhizome (Baizhu), Glycyrrhizae Radix Rhizome (Gancao), Poria (Fuling), Ophiopogonis Radix (Maidong), Hedyotidis Diffusae Herba (Baihuasheshecao), Codonopsis Radix (Dangshen), and Glehniae Radix (Beishashen). The properties of the herbs were mainly cold, warm, and mild. The flavors of the herbs were mainly sweet, bitter, and pungent. The main meridian tropisms were Lung Meridian of Hand-Taiyin, Spleen Meridian of Foot-Taiyin, and Stomach Meridian of Foot-Yangming. Conclusion. Applying clearing and tonifying method by targeting the lung and spleen was the most frequently used therapy in the treatment of NSCLC. This study offered a glimpse of unique views of traditional Chinese medicine on NSCLC and may benefit the treatment of NSCLC. [ABSTRACT FROM AUTHOR]

Background: Muscular performance is an important factor for the mechanical stability of lumbar spine in humans, in which, the co-contraction of lumbar muscles plays a key role. We hypothesized that when executing different daily living motions, the performance of the lumbar muscle co-contraction stabilization mechanism varies between patients with lumbar disc herniation (LDH) and healthy controls. Hence, in this study, co-contraction performance of lumbar muscles between patients with LDH and healthy subjects was explored to check if there are significant differences between the two groups when performing four representative movements.Methods: Twenty-six LDH patients (15 females, 11 males) and a control group of twenty-eight subjects (16 females, 12 males) were recruited. Surface electromyography (EMG) signals were recorded from the external oblique, lumbar multifidus, and internal oblique/transversus abdominis muscles during the execution of four types of movement, namely: forward bending, backward bending, left lateral flexion and right lateral flexion. The acquired EMG signals were segmented, and wavelet decomposition was performed followed by reconstruction of the low-frequency components of the signal. Then, the reconstructed signals were used for further analysis. Co-contraction ratio was employed to assess muscle coordination and compare it between the LDH patients and healthy controls. The corresponding signals of the subjects in the two groups were compared to evaluate the differences in agonistic and antagonistic muscle performance during the different motions. Also, sample entropy was applied to evaluate complexity changes in lumbar muscle recruitment during the movements.Results: Significant differences between the LDH and control groups were found in the studied situations (p < 0.05). During the four movements considered in this study, the participants of the LDH group exhibited a higher level of co-contraction ratio, lower agonistic, and higher antagonistic lumbar muscle activity (p < 0.01) than those of the control group. Furthermore, the co-contraction ratio of LDH patients was dominated by the antagonistic muscle activity during the movements, except for the forward bending motion. However, in the healthy control group, the agonistic muscle activity contributed more to the co-contraction ratio with an exception for the backward bending motion. Conversely, the sample entropy value was significantly lower for agonistic muscles of LDH group compared to the control group (p < 0.01) while the entropy value was significantly greater in antagonistic muscles (p < 0.01) during the four types of movement, respectively.Conclusions: Lumbar disc herniation patients exhibited numerous variations in the evaluated parameters that reflect the co-contraction of lumbar muscles, the agonistic and antagonistic muscle activities, and their respective sample entropy values when compared with the healthy control group. These variations could be due to the compensation mechanism that was required to stabilize the spine. The results of this study could facilitate the design of efficient rehabilitation methods for treatment of lumbar muscle dysfunctions. [ABSTRACT FROM AUTHOR]

Through a structure-guided core-refining approach, a series of novel imidazo[1,2- a ]pyrazine derivatives were designed, synthesized and evaluated as HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). Biological results of antiviral assay in MT-4 cell cultures showed that 12 target compounds displayed moderate activities against wild-type (wt) HIV-1 strain (III B ) with EC 50 values ranging from 0.26 μM to 19 μM. Among them, 4a and 5a were found to be the two most active analogues possessing EC 50 values of 0.26 μM and 0.32 μM respectively, comparable to delavirdine (DLV, EC 50 = 0.54 μM) and nevirapine (NVP, EC 50 = 0.31 μM) in a cell-based assay. Additionally, 9 compounds showed RT inhibitory activity superior to that of NVP. Moreover, some predicted drug-like properties of representative compounds 4a and 5a , as well as the structure-activity relationship (SAR) analysis were discussed in detail. The binding mode of compound 4a was investigated by molecular simulation studies. [ABSTRACT FROM AUTHOR]

Abstract: The development of new HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) offers the possibility of generating novel chemical entities of increased potency. Previous investigations in our laboratory resulted in the discovery of several novel series of arylazolylthioacetanilides as potent NNRTIs. In this study, based on the structure-based bioisosterism strategy, novel 1,2,4-triazin-6-yl thioacetamide derivatives were designed, synthesized and evaluated for their anti-HIV activity in MT-4 cells. Among them, the most promising compound was 8b15 with double-digit nanomolar activity against wild-type HIV-1 (EC50 =0.018±0.007μM) and moderate activity against the double mutant strain RES056 (EC50 =3.3±0.1μM), which indicated that 1,2,4-triazin-6-yl thioacetamide can be used as a novel scaffold to develop a new class of potent NNRTIs active against both wild-type and drug-resistant HIV-1 strains. In addition, preliminary structure–activity relationship (SAR) and molecular modeling results are also briefly discussed, which provide some useful information for the further design of novel NNRTIs. [Copyright &y& Elsevier]