Retrospective analysis of preoperative application of triple-modal pre-rehabilitation on postoperative recovery of colorectal cancer patients.

PURPOSE: To retrospectively analyze the difference between triple-modal pre-rehabilitation and common treatment in patients with colorectal cancer (CRC). METHODS: A total of 145 patients with CRC diagnosed by pathology and admitted to our hospital for surgery between June 2020 and June 2022 were included in the study. All patients were divided into two groups: the triple-modal pre-rehabilitation group (pre-rehabilitation group) and the common treatment group. The triple-modal pre-rehabilitation strategy included exercise (3-5 times per week, with each session lasting more than 50 min), nutritional support, and psychological support. The study was designed to assess the potential of the pre-rehabilitation intervention to accelerate postoperative recovery by assessing the 6-min walk test, nutritional indicators, and HADS score before and after surgery. RESULTS: The pre-rehabilitation intervention did not reduce the duration of initial postoperative recovery or the incidence of postoperative complications, but it did increase the patients' exercise capacity (as determined by the 6-min walk test), with the pre-rehabilitation group performing significantly better than the common group (433.0 (105.0) vs. 389.0 (103.5), P < 0.001). The study also found that triple-modal pre-rehabilitation was beneficial for the early recovery of nutritional status in surgical patients and improved anxiety and depression in patients after surgery, especially in those who had not received neoadjuvant therapy. CONCLUSION: The triple-modal pre-rehabilitation strategy is of significant importance for reducing stress and improving the functional reserve of patients with colorectal cancer (CRC) during the perioperative period. The results of our study provide further support for the integration of the triple-modal pre-rehabilitation strategy into the treatment and care of CRC patients.

Analysis of urethral blood flow by high-resolution laser speckle contrast imaging in a rat model of vaginal distension.

OBJECTIVE: To investigate the feasibility of laser speckle contrast imaging (LSCI) for monitoring urethral blood flow (UBF). MATERIALS AND METHODS: In this study, 18 healthy, virgin female Sprague-Dawley rats aged 8-week-old were used. The animals were divided into the sham group (n = 9) and the vaginal distension (VD) group (n = 9). The sham group underwent one catheterization of the vagina without distension and the VD group underwent one VD. Following the VD or sham treatment for one week, LSCI assessment of urethral blood flow was performed during bladder filling and leak point pressure (LPP) process. RESULTS: During the LPP process, in the VD group, the mean LPP was significantly lower than in the sham group (p < 0.05) and the mean UBF level was also significantly lower than in the sham group (p < 0.05) in the LPP condition. The mean relative change of UBF (Δ Flow) was significantly different between the sham group and VD group. The value was 0.646 ± 0.229 and 0.295 ± 0.19, respectively (p < 0.05). During the bladder filling process, the VD group had a significant lower mean UBF level than the sham group under full bladder conditions (p = 0.008). The mean ΔFlow was also significantly lower than in the sham group. The value was 0.115 ± 0.121 and 0.375 ± 0.127, respectively (p = 0.016). CONCLUSIONS: The results confirmed that LSCI was able to determine UBF in female rats. The VD group had lower baseline UBF and lower increases in UBF during bladder filling and LPP process compared with the sham group.

Tunable Fluorescence and Morphology of Aggregates Built from a Mechanically Bonded Amphiphilic Bistable [2]Rotaxane.

Advanced Organic Chemical Materials Co-constructed Mechanically bonded amphiphiles (MBAs), also known as mechanically interlocked molecules (MIMs), have emerged as an important kind of functional building block for the construction of artificial molecular machines and soft materials. Herein, a novel MBA, i. e., bistable [2]rotaxane H2 was designed and synthesized. In the solution state, H2 demonstrated pH and metal ion-responsive emissions due to the presence of a distance-dependent photoinduced electron transfer (PET) process and the fluorescence resonance energy transfer (FRET) process, respectively. Importantly, the amphiphilic feature of H2 has endowed it with unique self-assembly capability, and nanospheres were obtained in a mixed H2 O/CH3 CN solvent. Moreover, the morphology of H2 aggregates can be tuned from nanospheres to vesicles due to the pH-controlled shuttling motion-induced alternation of H2 amphiphilicity. Interestingly, larger spheres with novel pearl-chain-like structures from H2 were observed after adding stoichiometric Zn2+ . In particular, H2 shows pH-responsive emissions in its aggregation state, allowing the visualization of the shuttling movement by just naked eyes. It is assumed that the well-designed [2]rotaxane, and particularly the proposed concept of MBA shown here, will further enrich the families of MIMs, offering prospects for synthesizing more MIMs with novel assembly capabilities and bottom-up building dynamic smart materials with unprecedented functions.

Single-incision plus one-port laparoscopic gastrectomy versus conventional multi-port laparoscopy-assisted gastrectomy for gastric cancer: a retrospective study.

BACKGROUND: We compared short-term perioperative outcomes after single-incision plus one-port laparoscopic gastrectomy (SILG+1) and conventional multi-port laparoscopy-assisted gastrectomy (C-LAG) for gastric cancer. METHODS: The work was conducted between August 2017 and October 2019. A total of 90 patients with early or advanced gastric cancer were retrospectively analyzed: 43 patients of which underwent SILG+1, and 47 of which underwent C-LAG, respectively. These were divided into two groups: the total gastrectomy group (SILT+1 and C-LATG) and the distal gastrectomy group (SILD + 1 and C-LADG). The demographics, tumor characteristics, postoperative outcomes, and short-term complications of all enrolled patients were summarized and statistically analyzed. RESULTS: The mean incision length in SILT+1 group was 5.40 cm shorter than that in C-LATG group (3.15 ± 0.43 vs. 8.55 ± 2.72, P < 0.001). This comparison between the SILD + 1 and the C-LADG group produced comparable results. The SILT+1 group underwent a 56.32 min longer operation than the C-LATG group (273.03 ± 66.80 vs. 216.71 ± 82.61, P = 0.0205). SILG+1 group had better postoperative visual analog scale (VAS) and cosmetic score than those of the C-LATG group (P < 0.05). There were no significant differences in preoperative demographics or 30-day postoperative complication rates between the SILG+1 and C-LAG groups. Tumor-related index, including mass size, histological type, number of retrieved lymph nodes, pathological tumor-node-metastasis (TNM) stage, and proximal and distal edges were all equivalent between the SILG+1 and the C-LAG group. CONCLUSIONS: This retrospective study demonstrates the safety and feasibility of SILG+1 with D1+ or D2 lymphadenectomy for the treatment of early and advanced gastric cancers, compared with C-LAG.

Accuracy of the spontaneous breathing trial using a combined CPAP + PSV model to predict extubation outcomes in very preterm infants.

BACKGROUND: Very preterm infants often require mechanical ventilation. However, objective criteria to predict the outcomes of extubation in very premature neonates remain lacking. The aim of this study was to investigate the accuracy of the spontaneous breathing trial (SBT) using a combined model of continuous positive airway pressure (CPAP) and low-level pressure support ventilation (PSV) to predict the extubation outcomes of preterm infants with gestational age < 32 weeks. METHODS: Preterm infants with gestational age < 32 weeks, birth weight < 1500 g and requiring mechanical ventilation were selected for the study. All infants underwent a 10-minute SBT using CPAP combined with low-level PSV prior to the planned extubation. Then, the infants were extubated within 1 h after SBT. The outcomes of extubation were considered successful if the neonates did not require reintubation 72 h after extubation. RESULTS: A total of 119 eligible preterm infants were enrolled in the study, with a median gestational age of 28.9 (27.1-30.3) weeks and a median birth weight of 1100 (900-1350) g. In total, 101 of all infants had successful extubation, 18 of whom failed and eventually had to be reintubated. Of the 102 infants who achieved SBT, 99 were successfully extubated, and 15 of the 17 infants who did not pass SBT had failed extubation. Finally, the diagnostic value for SBT could be assessed with a sensitivity of 98%, a specificity of 83.3%, a positive predictive value of 97.1% and a negative predictive value of 88.2%. CONCLUSION: SBT using a combined CPAP + low-level PSV model can predict the outcomes of extubation in very preterm infants with high sensitivity and specificity.

Morphological and histological changes in the urethra after intraurethral nonablative erbium YAG laser therapy: an experimental study in beagle dogs.

The purpose of this study was to investigate the morphological and histological changes in the urethra in beagle dogs after intraurethral Er:YAG laser irradiation in nonablative mode to confirm the safety of this therapy. Six 2-year-old healthy female virgin beagle dogs (13 ± 1.51 kg) were used in this study. The animals were divided into 2 groups: the sham group, which received sham treatment (n = 3) involving insertion of an intraurethral cannula and laser delivery handpiece into the urethra without laser irradiation, and the experimental group (n = 3), which received intraurethral Er:YAG laser irradiation. The laser irradiation parameters were set according to clinical criteria (4 mm spot size, 1.5 J/cm2, 1.4 Hz, and 4 pulses) in nonablative mode. All animals received three sequential sessions at 4-week intervals. Urethrography and urethroscopy were performed in the 12th week and 13th week, respectively, after the first treatment. After urethroscopy, the animals were sacrificed, and urethral tissue was harvested for histological investigations. All procedures were performed under general anesthesia (40 mg/kg 3% sodium pentobarbital, i.v.). Transforming growth factor ß1 (TGF-ß1) and α-smooth muscle actin (α-SMA) expression levels were measured to evaluate the biochemical characteristics of the scar. Urethral stricture was not found by urethrography or urethroscopy in either group. Urethral epithelium thickness and collagen expression under the urethral mucosa were significantly increased in the experimental group compared with the sham group. However, there were no significant differences in TGF-ß1 and α-SMA expression between the experimental group and sham group (p > 0.05). Urethral stricture is not found in beagle dogs after clinically relevant intraurethral nonablative mode Er:YAG laser irradiation. Proliferation of urethral collagen and the urethral mucosa may be one of the mechanisms by which urine leakage symptoms can be improved.

Kushneria phosphatilytica sp. nov., a phosphate-solubilizing bacterium isolated from a solar saltern.

A Gram-stain-negative, motile, rod-shaped, non-endospore-forming, aerobic and halophilic bacterium, designated strain YCWA18T, was isolated from the sediment of Jimo-Daqiao saltern in China. This strain was able to grow at NaCl concentrations in the range 0.5-20 % (w/v) with optimum growth at 6 % (w/v) NaCl. Growth occurred at temperatures of 4-40 °C (optimum 28 °C) and pH 4.0-9.0 (optimum 7.0). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain YCWA18T belonged to the genus Kushneria and shared the highest sequence similarity of 98.7 % with Kushneria sinocarnis DSM 23229T. Moreover, the phylogenetic analysis based on the 23S rRNA gene sequence also confirmed the phylogenetic position of this novel strain. The predominant fatty acids were C16 : 0, C17 : 0 cyclo and C12 : 0 3-OH. The major isoprenoid quinone was Q-9 (94.2 %) and the polar lipids were diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), phosphatidylethanolamine (PE), an unidentified aminolipid (AL), an unidentified phospholipids (PL) and two unidentified lipids (L). The complete genome of strain YCWA18T consisted of a single, circular chromosome of 3 624 619 bp, with an average G+C content of 59.1 mol%. A genome-based phylogenetic tree constructed using an up-to-date bacterial core gene set (UBCG) showed that strain YCWA18T formed a clade with K. sinocarnis DSM 23229T. However, the level of the ANI and dDDH values between strain YCWA18T and K. sinocarnis DSM 23229T were 82.3 and 24.6 %, respectively, which were low enough to distinguish strain YCWA18T from K. sinocarnis DSM 23229T. Overall, based on the phenotypic, chemotaxonomic, phylogenetic and genomic analyses, strain YCWA18T represents a novel species of genus Kushneria. The name Kushneria phosphatilytica sp. nov. is proposed, with the type strain YCWA18T (=CGMCC 1.9149T=NCCB 100306T).

An N-heterocyclic carbene-catalyzed switchable reaction of 9-(trimethylsilyl)fluorene and aldehydes: chemoselective synthesis of dibenzofulvenes and fluorenyl alcohols.

An N-heterocyclic carbene-catalyzed synthesis of dibenzofulvenes and fluorenyl alcohols was developed. In the presence of 10 mol% NHC (1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) and 4 Å molecular sieves, 9-(trimethylsilyl)fluorene undergoes an olefination reaction with aldehydes to produce dibenzofulvenes in 43-99% yields. However, on reducing the NHC loading to 1 mol% and with the addition of water, 9-(trimethylsilyl)fluorene selectively undergoes nucleophilic addition with aldehydes to afford fluorenyl alcohols in 40-95% yields.

Evidence-based Guideline for Therapeutic Drug Monitoring of Vancomycin: 2020 Update by the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society.

BACKGROUND: Clinical practice guidelines or recommendations often require timely and regular updating as new evidence emerges, because this can alter the risk-benefit trade-off. The scientific process of developing and updating guidelines accompanied by adequate implementation can improve outcomes. To promote better management of patients receiving vancomycin therapy, we updated the guideline for the therapeutic drug monitoring (TDM) of vancomycin published in 2015. METHODS: Our updated recommendations complied with standards for developing trustworthy guidelines, including timeliness and rigor of the updating process, as well as the use of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. We also followed the methodology handbook published by the National Institute for Health and Clinical Excellence and the Spanish National Health System. RESULTS: We partially updated the 2015 guideline. Apart from adults, the updated guideline also focuses on pediatric patients and neonates requiring intravenous vancomycin therapy. The guideline recommendations involve a broadened range of patients requiring TDM, modified index of TDM (both 24-hour area under the curve and trough concentration), addition regarding the necessity and timing of repeated TDM, and initial dose for specific subpopulations. Overall, 1 recommendation was deleted and 3 recommendations were modified. Eleven new recommendations were added, and no recommendation was made for 2 clinical questions. CONCLUSIONS: We updated an evidence-based guideline regarding the TDM of vancomycin using a rigorous and multidisciplinary approach. The updated guideline provides more comprehensive recommendations to inform rational and optimized vancomycin use and is thus of greater applicability.

Complete Genome Sequence of Strain YCSC6, a Marine Bacterium Isolated from Saturated Saltpan with Activity Against Uronema marinum.

Salinivibrio proteolyticus strain YCSC6 was isolated from a saturated saltpan and demonstrated to have strong insecticidal activity against turbot's pathogenic ciliate-Uronema marinum. In this study, we sequenced its complete genome. Results showed that it consists of two circular chromosomes: 2.49 Mbps and 0.74 Mbps, respectively. It encodes 3429 protein-coding sequences. Biosynthetic gene clusters predicted to synthesize bacteriocins and antimicrobial peptides were discovered, which might be the key factors to lyse and kill U. marinum. The complete genome sequence of strain YCSC6 provides insights into the fundamental genetic potential for elucidating its insecticidal mechanism against U. marinum.

Nrf2 promotes breast cancer cell migration via up-regulation of G6PD/HIF-1α/Notch1 axis.

Abnormal metabolism of tumour cells is closely related to the occurrence and development of breast cancer, during which the expression of NF-E2-related factor 2 (Nrf2) is of great significance. Metastatic breast cancer is one of the most common causes of cancer death worldwide; however, the molecular mechanism underlying breast cancer metastasis remains unknown. In this study, we found that the overexpression of Nrf2 promoted proliferation and migration of breast cancers cells. Inhibition of Nrf2 and overexpression of Kelch-like ECH-associated protein 1 (Keap1) reduced the expression of glucose-6-phosphate dehydrogenase (G6PD) and transketolase of pentose phosphate pathway, and overexpression of Nrf2 and knockdown of Keap1 had opposite effects. Our results further showed that the overexpression of Nrf2 promoted the expression of G6PD and Hypoxia-inducing factor 1α (HIF-1α) in MCF-7 and MDA-MB-231 cells. Overexpression of Nrf2 up-regulated the expression of Notch1 via G6PD/HIF-1α pathway. Notch signalling pathway affected the proliferation of breast cancer by affecting its downstream gene HES-1, and regulated the migration of breast cancer cells by affecting the expression of EMT pathway. The results suggest that Nrf2 is a potential molecular target for the treatment of breast cancer and targeting Notch1 signalling pathway may provide a promising strategy for the treatment of Nrf2-driven breast cancer metastasis.

Knockdown on aPKC-ι inhibits epithelial-mesenchymal transition, migration and invasion of colorectal cancer cells through Rac1-JNK pathway.

BACKGROUND: Atypical protein kinase C-ι (aPKC-ι) is an oncogenic factor, and required for the epithelial-mesenchymal transition (EMT) of different types of cancer. Our study aimed to investigate the role of aPKC-ι in the EMT, migration and invasion of colorectal cancer (CRC) cells. METHODS: Expression of aPKC-ι was evaluated in CRC cell lines treated with TGF-ß1 using qPCR and western blot. After aPKC-ι was knocked down using shRNA, migration and invasion abilities of CRC cell lines were evaluated by wound healing assay and transwell assay, respectively. Activation status of downstream signaling factors of aPKC-ι, including Rac1, JNK, STAT3 and ß-catenin, was measured using western blot. Furthermore, auranofin, an aPKC-ι inhibitor, was used to treat CRC cell lines to investigate its possible inhibition on the EMT of CRC cell lines, as well as on the expression of aPKC-ι and its downstream signaling factors. RESULTS: TGF-ß1 induced the expression of aPKC-ι in CRC cells, and knockdown on aPKC-ι inhibited the TGF-ß1-induced EMT, migration and invasion of CRC cells. Interestingly, Rac1 GTPase level was decreased when aPKC-ι was knocked down, and overexpression of Rac1G12V rescued the cell EMT, migration and invasion in CRC cells as inhibited by sh-aPKC-ι. Moreover, knockdown on aPKC-ι suppressed the phosphorylation of JNK and STAT3, and nuclear translocation of ß-catenin. The aPKC- ι inhibitor, Auranofin, showed similar inhibitory effects as aPKC-ι knockdown. CONCLUSION: Knockdown on aPKC-ι inhibited the EMT, migration and invasion of CRC cells through suppressing of Rac1-JNK pathway. Those findings indicate that aPKC-ι may serve as a novel therapeutic target for CRC.

N-Heterocyclic carbene-catalyzed diastereoselective synthesis of sulfenylated indanes via sulfa-Michael-Michael (aldol) cascade reactions.

N-Heterocyclic carbene (NHC)-catalyzed diastereoselective synthesis of multisubstituted sulfenylated indanes has been developed. In the presence of 1 mol% NHC, various thiols underwent the sulfa-Michael-Michael cascade reaction with benzenedi(enones) efficiently to form the carbon-sulfur bond and construct sulfenylated indanes in good to excellent yields with high diastereoselectivity. In addition, the NHC-catalyzed sulfa-Michael-aldol cascade reaction between o-formyl chalcone and thiols has also been demonstrated to afford sulfenylated indanes with a free hydroxyl group in moderate yields and good diastereoselectivity.

ERα Gene Promoter Methylation in Cognitive Function and Quality of Life of Patients With Alzheimer Disease.

OBJECTIVE: Alzheimer disease (AD) has been recognized as a progressive neurodegenerative disorder. This study aims to investigate the effects of estrogen receptor α (ERα) gene promoter methylation on the cognitive function and quality of life (QOL) of patients with AD. METHODS: A total of 132 patients with AD and 135 healthy individuals were recruited for this study. The DNA in the peripheral blood was extracted and treated with bisulfite; then methylation-specific polymerase chain reaction and reverse transcription quantitative polymerase chain reaction were performed to determine the methylation status of ERα and ERα messenger RNA (mRNA) expression, respectively. Mini-Mental State Examination (MMSE), activities of daily living (ADL), and Quality of Life-Alzheimer Disease scale were employed to evaluate the cognitive functions, ADL, and QOL of the participants. RESULTS: The methylation group showed a decrease in ERα mRNA expression. The MMSE and ADL scores were indicative of a worse cognitive function in the methylation group. The ERα promoter methylated patients showed a higher rate of abnormal ADL score, while patients in the nonmethylation group enjoyed a better QOL. CONCLUSIONS: The ERα promoter methylation is related to impaired cognitive function and QOL of patients with AD by inhibiting ERα mRNA expression and transcription.

[Correlation of aldo-keto reductases with prostate cancer and intervention with traditional Chinese medicine].

The androgen receptor signaling pathway is a key factor in the development and progression of prostate cancer. Aldo-keto reductases AKR1C1-AKR1C4 play an important role in the synthesis and metabolism of androgens in the body, and their expressions influence the androgen receptor signaling pathway and consequently the development and progression of prostate cancer. For the treatment of androgen-resistant prostate cancer, which cannot be cured currently, Chinese medicine and phytotherapy are receiving more and more attention for the mild, long-lasting and multi-target advantages of the small molecules of traditional Chinese medicine. This review summarizes the roles of aldo-keto reductases in the progression of prostate cancer and compares the anti-tumor activities of small molecules in Chinese medicine targeting aldo-keto reductases, hoping to provide a basis for the discovery of new targets for prostate cancer and the development of anti-tumor drugs.

Loss of TET1 facilitates DLD1 colon cancer cell migration via H3K27me3-mediated down-regulation of E-cadherin.

Epigenetic modifications such as histone modifications and cytosine hydroxymethylation are linked to tumorigenesis. Loss of 5-hydroxymethylcytosine (5 hmC) by ten-eleven translocation 1 (TET1) down-regulation facilitates tumor initiation and development. However, the mechanisms by which loss of TET1 knockdown promotes malignancy development remains unclear. Here, we report that TET1 knockdown induced epithelial-mesenchymal transition (EMT) and increased cancer cell growth, migration, and invasion in DLD1 cells. Loss of TET1 increased EZH2 expression and reduced UTX-1 expression, thus increasing histone H3K27 tri-methylation causing repression of the target gene E-cadherin. Ectopic expression of the H3K27 demethylase UTX-1 or EZH2 depletion both impeded EZH2 binding caused a loss of H3K27 methylation at epithelial gene E-cadherin promoter, thereby suppressing EMT and tumor invasion in shTET1 cells. Conversely, UTX-1 depletion and ectopic expression of EZH2 enhanced EMT and tumor metastasis in DLD1 cells. These findings provide insight into the regulation of TET1 and E-cadherin and identify EZH2 as a critical mediator of E-cadherin repression and tumor progression.

Anti-inflammatory fusicoccane-type diterpenoids from the phytopathogenic fungus Alternaria brassicicola.

Altering the cultivation conditions, such as temperature, media compositions, illumination, aeration, the shape of the culturing flask, etc., is regarded as a useful strategy for the exploitation of structurally novel and bioactive secondary metabolites, which inspired us to explore the chemical and pharmacological diversities from the genetically powerful fungus Alternaria brassicicola. As a result, twelve fusicoccane-type diterpenoids, including eight new ones, termed brassicicenes Q-X (1-8), were isolated from a modified rice medium. Biosynthetically, all these compounds were derived from the mevalonic acid (MVA) pathway, and their structures incorporating absolute configurations were assigned by the interpretation of spectroscopic (HRESIMS and 1D and 2D NMR) analyses, chemical conversion, a modified Mosher's method, 13C NMR calculation, and single-crystal X-ray diffraction (Cu Kα). Structurally, compound 1 was an unusual 16-nor-dicyclopenta[a,d]cyclooctane diterpenoid bearing a fused cyclopent-2-en-1-one moiety. In addition, compound 3 was found to show significant anti-inflammatory activity against the production of NO, TNF-α, and IL-1ß at 10 µM. Further western blot and immunofluorescence experiments found the mechanism of action to be that 3 inhibited the NF-κB-activated pathway, highlighting it as a promising starting point for the development of new anti-inflammatory agents.

Development of Functional Phthalocyanine-Based Associate towards an Effective Fluorimetric Detection of Hg(II).

In acidic media, cationic phthalocyanine Alcian blue 8GX, has an efficient fluorescence quenching effect on anionic phthalocyanine tetrasulphoaluminium phthalocyanines (AlS4Pc), forming an almost non-fluorescent associate. Based on this discovery, a red-emitting fluorescent probe consisted of AlS4PC and Alcian blue 8GX has been developed through molecular assembly. Further studies indicated that the presence of Hg(II) ion has a significant fluorescence recovery effect of the probe. Notably, only Hg(II) can significantly restore the fluorescence of AlS4Pc-Alcian blue 8GX system which was revealed from the screening experiments of common metal ions, which confirmed that the fluorescence recovery by other metal ions is very weak or even unrestored, showing high specificity and sensitivity AlS4Pc-Alcian blue 8GX to Hg(II). Thus, a new fluorimetry for Hg(II) with high specificity and high sensitivity in a wide concentration range has been established using AlS4Pc-Alcian blue 8GX associate as a red-emitting fluorescent probe. It is more noteworthy that this study opens a new way for development and application of functional phthalocyanine based red-emitting fluorescent probes.

PKM2-mediated inhibition of autophagy facilitates Tat's inducing HIV-1 transactivation.

Considerable evidence has shown that autophagy has an important role in HIV-1 infection. However, it is still unknown whether metabolism-regulated autophagy pathway is involved in Tat-mediated HIV-1 transactivation. This study demonstrated that treatment of Tat in TZM-bl cells significantly down-regulated protein levels of Beclin-1, Atg-5, Atg-7, and LC3B-II and up-regulated of p62 levels. Blockage of autophagy enhanced Tat-induced HIV-1 transactivation in TZM-bl cells. Moreover, we found that Tat activated the Akt/mTOR and inhibited AMPK signaling pathway that was related to its up-regulation of PKM2 expression. In addition, we showed that PI3K/AKT activation and AMPK inhibtion was required for the PKM2-mediated inhibition of autophagy in Tat-treated TZM-bl cells. In conclusion, our data reveals that PKM2-mediated autophagy inhibition is required for Tat-mediated HIV-1 transactivation. Metabolism-related autophagic pathway may act as a promising diagnostic and therapeutic tool for HIV-1 infection in the future.

N-Heterocyclic carbene-catalyzed stereoselective construction of olefinic carbon-sulfur bonds via cross-coupling reaction of gem-difluoroalkenes and thiols.

A novel organocatalytic olefinic carbon-sulfur bond forming reaction was developed. Under the catalysis of 10 mol% stable N-heterocyclic carbene, thiols undergo direct nucleophilic substitution reaction with gem-difluoroalkenes to produce α-fluorovinyl thioethers in high yields with excellent Z-selectivity. In this process, bases are not necessary.