Loss of SHROOM3 affects neuroepithelial cell shape through regulating cytoskeleton proteins in cynomolgus monkey organoids.

Neural tube defects (NTDs) are severe congenital neurodevelopmental disorders arising from incomplete neural tube closure. Although folate supplementation has been shown to mitigate the incidence of NTDs, some cases, often attributable to genetic factors, remain unpreventable. The SHROOM3 gene has been implicated in NTD cases that are unresponsive to folate supplementation; at present, however, the underlying mechanism remains unclear. Neural tube morphogenesis is a complex process involving the folding of the planar epithelium of the neural plate. To determine the role of SHROOM3 in early developmental morphogenesis, we established a neuroepithelial organoid culture system derived from cynomolgus monkeys to closely mimic the in vivo neural plate phase. Loss of SHROOM3 resulted in shorter neuroepithelial cells and smaller nuclei. These morphological changes were attributed to the insufficient recruitment of cytoskeletal proteins, namely fibrous actin (F-actin), myosin II, and phospho-myosin light chain (PMLC), to the apical side of the neuroepithelial cells. Notably, these defects were not rescued by folate supplementation. RNA sequencing revealed that differentially expressed genes were enriched in biological processes associated with cellular and organ morphogenesis. In summary, we established an authentic in vitro system to study NTDs and identified a novel mechanism for NTDs that are unresponsive to folate supplementation.

Single-cell transcriptome and metagenome profiling reveals the genetic basis of rumen functions and convergent developmental patterns in ruminants.

The rumen undergoes developmental changes during maturation. To characterize this understudied dynamic process, we profiled single-cell transcriptomes of about 308,000 cells from the rumen tissues of sheep and goats at 17 time points. We built comprehensive transcriptome and metagenome atlases from early embryonic to rumination stages, and recapitulated histomorphometric and transcriptional features of the rumen, revealing key transitional signatures associated with the development of ruminal cells, microbiota, and core transcriptional regulatory networks. In addition, we identified and validated potential cross-talk between host cells and microbiomes and revealed their roles in modulating the spatiotemporal expression of key genes in ruminal cells. Cross-species analyses revealed convergent developmental patterns of cellular heterogeneity, gene expression, and cell-cell and microbiome-cell interactions. Finally, we uncovered how the interactions can act upon the symbiotic rumen system to modify the processes of fermentation, fiber digestion, and immune defense. These results significantly enhance understanding of the genetic basis of the unique roles of rumen.

[Application of dynamic contrast enhanced status in multiparametric magnetic resonance imaging for prostatic cancer with PI-RADS 4 lesion].

OBJECTIVE: To evaluate the diagnostic value of dynamic contrast enhanced (DCE) of multiparametric magnetic resonance imaging (mpMRI) for prostate imaging reporting and data system (PI-RADS) 4 lesion in prostate peripheral zone. METHODS: The clinical data of patients with PI-RADS 4 lesion in prostate peripheral zone who underwent prostate biopsy from January 2018 to September 2021 in Peking University First Hospital were retrospectively included. According to DCE status, the patients were divided into the conventional group (4 points for diffusion-weighted imaging) and the comprehensive group (3 points for diffusion-weighted imaging + 1 point for DCE positive). Pearson's chi-square test or Fisher's exact test for comparison was conducted between prostate cancer and non-cancer patients. Univariate and multivariate Logistic regression were performed to analyze the correlation of positive biopsy with age, total prostate specific antigen (PSA), free PSA/total PSA (f/tPSA), prostate volume (PV), PSA density (PSAD) and DCE status. RESULTS: Among the 267 prostate biopsy patients, 217 cases were diagnosed as prostatic cancer (81.27%) and 50 cases were non-cancer (18.73%). Statistical analysis between the prostatic cancer group and the non-cancer group showed that there were significant differences in age, tPSA, PV and PSAD (all P < 0.05), but no significant differences in f/tPSA between the two groups. About different PI-RADS 4 lesion groups, the conventional group and the comprehensive group showed significant difference in biopsy results (P=0.001), and the conventional group had a higher positive rate. The PV of comprehensive group was larger than that of the conventional group. Among the prostate cancer patients diagnosed by biopsy, statistical analysis between the conventional group and comprehensive group showed that there were not significant differences in International Society of Urological Pathology (ISUP) grade and distinguishing clinically significant prostate cancer (all P > 0.05). Logistic univariate analysis showed that the diagnosis of prostate cancer was related to age, tPSA, f/tPSA, PV and DCE group status (all P < 0.05). Multivariate analysis showed that age, tPSA, PV and DCE group status (all P < 0.05) were independent risk factors for the diagnosis of prostatic cancer. CONCLUSION: tPSA, f/tPSA, PV and PSAD are the indicators to improve the diagnosis of prostatic cancer with PI-RADS 4 lesion in peripheral zone lesions. DCE status is worth considering, so that we can select patients for biopsy more accurately, reduce the rate of missed diagnosis of prostate cancer as well as avoid unnecessary prostate puncture.

Nuclear PARP1-Targeted Photosensitizer as a Dual-Mode DNA-Damaging Agent and Immune Activator for Tumor Ablation.

Photodynamic therapy is a promising cancer therapeutic method that can damage DNA via photoinduced reactive oxygen species production. However, tumor cells can initiate DNA repair pathways to resist oxidative damage. In this study, a nuclear-targeted photosensitizer PARP-PS with a poly (ADP-ribose) polymerase 1 (PARP1) inhibitory effect is developed based on the reported PARP1 inhibitor, rucaparib. As a dual-mode DNA-damaging agent, PARP-PS damages DNA upon photoirradiation and enhances oxidative DNA damage by blocking the DNA repair pathway via PARP1 inhibition and degradation. Both in vitro and in vivo investigations demonstrate that PARP-PS exhibits high antitumor activity with few side effects in breast cancer. In addition, PARP-PS can act as an immunogenic cell death inducer to activate immune responses characterized by the promotion of cytotoxic T lymphocyte activation and tumor infiltration. Therefore, PARP-PS is a potential multimodal antitumor agent with synergistic phototherapeutic, chemotherapeutic, and immunotherapeutic effects.

Ligand-Directed Photodegradation of Interacting Proteins: Oxidative HER2/HER3 Heterodimer Degradation with a Lapatinib-Derived Photosensitizer.

In this work, we described a photocatalytic approach, termed ligand-directed photodegradation of interacting proteins (LDPIP), for efficient protein-protein heterodimer degradation. This LDPIP approach utilizes a combination of a photosensitizing protein ligand and appropriate light and molecular oxygen to induce oxidative damage to the ligand-binding protein as well as its interacting protein partner. As a showcase study, a photosensitizing HER2 ligand HER-PS-I was rationally designed based on the FDA-approved HER2 inhibitor lapatinib to efficiently degrade HER2 together with its interacting protein partner HER3, which is thought to induce HER2-targeted therapy resistance and difficult to target by small molecules. HER-PS-I exhibited excellent anticancer activity against drug-resistant MDA-MB-453 cells and its three-dimensional multicellular spheroids. We hope that this LDPIP approach would find more applications in degrading proteins that are thought undruggable or difficult to drug.

Lysosome-targeting phenalenones as efficient type I/II photosensitizers for anticancer photodynamic therapy.

Development of safe and effective photosensitizers is important for enhancing the efficacy of photodynamic cancer therapy. Phenalenone is a type II photosensitizer with a high singlet oxygen quantum yield; however, its short UV absorption wavelength hinders its application in cancer imaging and in vivo photodynamic therapy. In this study, we report a new redshift phenalenone derivative, 6-amino-5-iodo-1H-phenalen-1-one (SDU Red [SR]), as a lysosome-targeting photosensitizer for triple-negative breast cancer therapy. SDU Red produced singlet oxygen (Type II reactive oxygen species [ROS]) and superoxide anion radicals (Type I ROS) upon light irradiation. It also exhibited good photostability and a remarkable phototherapeutic index (PI > 76) against triple-negative breast cancer MDA-MB-231 cancer cells. Additionally, we designed two amide derivatives, SRE-I and SRE-II, with decreased fluorescence and photosensitizing capabilities based on SDU Red as activatable photosensitizers for photodynamic cancer therapy. SRE-I and SRE-II could be further converted into the active photosensitizer SDU Red via carboxylesterase-catalyzed amide bond cleavage. Moreover, SDU Red and SRE-II induced DNA damage and cell apoptosis in the presence of light. Therefore, SRE-II can act as a promising theranostic agent for triple-negative breast cancer.

Sequential acid/reduction response of triblock copolymeric nanomicelles to release camptothecin and toll-like receptor 7/8 agonist for orchestrated chemoimmunotherapy.

BACKGROUND: Immunosuppressive tumor immune microenvironment (TIME) lowers immunotherapy effectiveness. Additionally, low penetration efficiency and unpredictable drug release in tumor areas restrict tumor therapy. METHODS: A triblock copolymeric micelle (NanoPCPT+PIMDQ) was developed to carry the chemotherapeutic drug camptothecin (CPT) and the TLR7/8 agonist 1-(4-(aminomethyl)benzyl)-2-butyl-1H-imidazo[4,5-c] quinoline-4-amine (IMDQ) to achieve deep tumor penetration and on-demand drug release by responding to acid and reduction stimuli sequentially. The synergistic antitumour efficacy of NanoPCPT+PIMDQ was assessed both in vitro and in vivo. RESULTS: NanoPCPT+PIMDQ is composed of a hydrophilic PEG(polyethylene glycol) outer layer, an acid-sensitive EPEMA middle layer, and a drug inner core. Upon intratumoral injection, (i) NanoPCPT+PIMDQ first responds to the acidic tumor microenvironment and disintegrates to PIMDQ and PCPT, penetrating deep regions of the tumor; (ii) tumor cells are killed by the released CPT; (iii) DCs are activated by PIMDQ to increase the infiltration of cytotoxic T lymphocyte (CTL); and (iv) both downregulated Foxp3+ Tregs by CPT and repolarized M2 macrophages by PIMDQ can relieve the TIME. CONCLUSION: This pH/GSH-responsive triblock polymer-drug conjugate reduces immunosuppression and enhances the infiltration of CTLs by codelivering CPT and IMDQ in a controllable manner, providing a promising platform for synergistic tumor chemoimmunotherapy.

microRNA-145-5p attenuates acute lung injury via targeting ETS2.

The protective effect of microRNA (miR)-145-5p in acute lung injury (ALI) has been discovered previously. Thus, in this study, we attempted to further investigate the mechanism of miR-145-5p in ALI through the downstream E26 transformation-specific proto-oncogene 2 (ETS2)/transforming growth factor ß1 (TGF-ß1)/Smad pathway. A lipopolysaccharide (LPS)-induced ALI rat model was established. The expression of miR-145-5p in ALI rat lung tissues was up-regulated. Afterward, pathological damage in the lung tissue, the wet/dry (W/D) ratio, apoptosis, and serum inflammatory factor contents were observed. miR-145-5p, ETS2, TGF-ß1, Smad2/3, and phosphorylated Smad2/3 levels were measured in rats. miR-145-5p expression was down-regulated, ETS2 expression was up-regulated, and the TGF-ß1/Smad pathway was activated in LPS-exposed rats. Overexpression of miR-145-5p inactivated the TGF-ß1/Smad pathway and attenuated ALI, as reflected by relieved pathological damage, a decreased W/D ratio, reduced apoptosis, and suppressed inflammatory response. In contrast, loss of miR-145-5p or elevated ETS2 levels worsened ALI and activated the TGF-ß1/Smad pathway. Moreover, elevation of ETS2 diminished miR-145-5p-mediated protection against ALI. Evidently, miR-145-5p negatively regulates ETS2 expression and inactivates the TGF-ß1/Smad pathway to ameliorate ALI in rats.

The Protective Effects of Zornia diphylla (L.) Pers. Against Acute Liver Injury Induced by Carbon Tetrachloride in Mice.

Background: Zornia diphylla (L.) Pers. (ZDP) is a traditional Chinese herbal medicine that has been used for several decades to treat patients with liver diseases. Whether ZDP is best administered as a single agent or adjunctive therapy has yet to be determined as does the mechanism whereby it exerts its effects on antagonizing acute liver injury (ALI). Aim of the study: To investigate the protective effects of ZDP on ALI induced by carbon tetrachloride (CCl4) and the potential underlying mechanisms. Materials and Methods: Sixty adult mice were randomized into six study groups (n = 10/group). Three groups were treated with different concentrations of ZDP (2.5, 1.25, 0.625 g/kg), one with bifendate (0.0075 g/kg) alone (positive control) and one with physiologic saline (normal, negative control). All groups were treated for 14 days. Two hours after the last administration, the normal group received an intraperitoneal injection of peanut oil, and the other five groups received an intraperitoneal injection of an equal dose of CCl4 peanut oil solution. At 24 h, the liver index, histology and serum or tissue levels and/or protein expression of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), alkaline phosphatase (ALP), superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), glutathione (GSH), Akt, phosphorylated Akt (p-Akt), nuclear factor kappa B p65 (NF-κB p65), inhibitor of NF-κB α (IκB-α), interleukin-1 ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), E-cadherin and vimentin were determined. Results: Compared to the model controls, the degree of inflammatory cell infiltration and hepatocyte injury of liver tissue was relieved in the bifendate and three ZDP groups; liver index in the ZDP (2.5, 1.25 g/kg) groups and serum liver function indices in the ZDP (2.5, 1.25 and 0.625 g/kg) groups were decreased; antioxidants SOD, CAT and GSH in liver tissue were increased but the lipid peroxidation index MDA was decreased; protein expression of inflammatory cytokines Akt, p-Akt, NF-κB p65, IκB-α, IL-1ß, IL-6 and TNF-α in the liver was ameliorated, and E-cadherin expression was increased. The results of liver histopathology also showed that ZDP had a significant effect on ALI. Conclusion: ZDP has obvious protective effects on CCl4-induced ALI as a single therapy and appears to act by inhibiting oxidation, reducing the release of inflammatory factors and promoting hepatocyte repair.

Chromosome-Scale Genome Assembly for Chinese Sour Jujube and Insights Into Its Genome Evolution and Domestication Signature.

Sour or wild jujube fruits and dried seeds are popular food all over the world. In this study, we reported a high-quality genome assembly of sour jujube (Ziziphus jujuba Mill. var. spinosa), with a size of 406 Mbp and scaffold N50 of 30.3 Mbp, which experienced only γ hexaploidization event, without recent genome duplication. Population structure analysis identified four jujube subgroups (two domesticated ones, i.e., D1 in West China and D2 in East/SouthEast China, semi-wild, and wild), which underwent an evolutionary history of a significant decline of effective population size during the Last Glacial Period. The respective selection signatures of three subgroups were discovered, such as strong peaks on chromosomes #3 in D1, #1 in D2, and #4 in wild. Genes under the most significant selection on chromosomes #4 in wild were confirmed to be involved in fruit variations among jujube accessions, in transcriptomic analysis. Our study offered novel insights into the jujube population structure and domestication and provided valuable genomic resources for jujube improvement in stress response and fruit flavor in the future.

Extracellular matrix-related genes play an important role in the progression of NMIBC to MIBC: a bioinformatics analysis study.

Bladder cancer is the 11th most common cancer in the world. Bladder cancer can be roughly divided into muscle invasive bladder cancer (MIBC) and non-muscle invasive bladder cancer (NMIBC). The aim of the present study was to identify the key genes and pathways associated with the progression of NMIBC to MIBC and to further analyze its molecular mechanism and prognostic significance. We analyzed microarray data of NMIBC and MIBC gene expression datasets (GSE31684) listed in the Gene Expression Omnibus (GEO) database. After the dataset was analyzed using R software, differentially expressed genes (DEGs) of NMIBC and MIBC were identified. These DEGs were analyzed using Gene Ontology (GO) enrichment, KOBAS-Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and protein-protein interaction (PPI) analysis. The effect of these hub genes on the survival of bladder cancer patients was analyzed in The Cancer Genome Atlas (TCGA) database. A total of 389 DEGs were obtained, of which 270 were up-regulated and 119 down-regulated. GO and KEGG pathway enrichment analysis revealed that DEGs were mainly involved in the pathway of protein digestion and absorption, extracellular matrix (ECM) receiver interaction, phantom, toll-like receptor (TLR) signaling pathway, focal adhesion, NF-κB signaling pathway, PI3K/Akt signaling pathway, and other signaling pathways. Top five hub genes COL1A2, COL3A1, COL5A1, POSTN, and COL12A1 may be involved in the development of MIBC. These results may provide us with a further understanding of the occurrence and development of MIBC, as well as new targets for the diagnosis and treatment of MIBC in the future.

Comparative Study of Retroperitoneal Laparoscopic Versus Open Ipsilateral Nephrectomy After Percutaneous Nephrostomy: A Multicenter Analysis.

Purpose: To investigate the feasibility of retroperitoneal laparoscopic ipsilateral nephrectomy of a benign nonfunctional kidney after percutaneous nephrostomy, and to compare this method with open surgery. Materials and Methods: Data from 70 patients who underwent simple nephrectomy from January 2014 to October 2018 at three large centers were retrospectively analyzed. All patients underwent percutaneous nephrostomy because of renal or ureteral calculi with severe hydronephrosis or pyonephrosis. Simple nephrectomy was performed via retroperitoneal laparoscopic surgery (retroperitoneal laparoscopic group; n = 33) or open surgery (open group; n = 37). The retroperitoneal laparoscopic and open groups were compared regarding preoperative variables (age, sex, location of surgery, hypertension, diabetes, BMI, preoperative serum creatinine level, American Society of Anesthesiologists (ASA) grade, fistula duration, fistula size, number of fistulae, and urinary tract infection), and perioperative variables (operation time, intraoperative blood loss, postoperative drainage volume, catheter indwelling time, gastrointestinal function recovery time, duration of bedrest, duration of postoperative hospitalization, postoperative hemoglobin decline, perioperative transfusion, and postoperative complications). Results: The retroperitoneal laparoscopic group included more patients with hydronephrosis, while the open group included more patients with pyonephrosis. There were no significant differences between the two groups in age (P = .813), sex (P = .729), location of surgery (P = .345), hypertension (P = .271), diabetes (P = .394), BMI (P = .798), preoperative serum creatinine level (P = .826), ASA grade (P = .820), fistula duration (P = .108), fistula size (P = .958), number of fistulae (P = .925), urinary tract infection (P = .111), or operative time (P = .851). The retroperitoneal laparoscopic group had significantly lesser intraoperative blood loss (P = .007), postoperative drainage volume (P = .008), shorter catheter indwelling time (P = .002), gastrointestinal function recovery time (P < .001), duration of bedrest (P < .001), and duration of postoperative hospitalization (P < .001), and lesser postoperative hemoglobin decline (P = .035) compared with the open group. Conclusions: Retroperitoneal laparoscopic ipsilateral nephrectomy is feasible for a benign nonfunctional kidney after percutaneous nephrostomy. The surgical method should be selected based on the surgeon's experience and the specific situation of the patient.

Evaluation of three stone-scoring systems for predicting SFR and complications after percutaneous nephrolithotomy: a systematic review and meta-analysis.

BACKGROUND: Clinical studies assessing the feasibility and accuracy of three stone scoring systems's (SSSs: Guy's stone score, CROES nomogram and S.T.O.N.E nephrolithometry scoring system) have reported contradictory outcomes. This systematic evaluation was performed to obtain comprehensive evidence with regard to the feasibility and accuracy of three SSSs. METHODS: A systematic search of Embase, Pubmed, Medline, and the Cochrane Library was conducted to identify studies that compared three SSSs up to Mar 2018. Patients were categorized according to stone free (SF) and no-stone free (NSF), Outcomes of interest included perioperative variables, stone-free rate (SFR), and complications. RESULTS: Ten studies estimating three SSSs were included for meta-analysis. The results showed that SF patients had a significantly lower proportion of male (OR = 1.48, P = 0.0007), lower stone burden (WMD = -504.28, P < 0.0001), fewer No of involved calyces (OR = -1.23, P = 0.0007) and lower proportion of staghorn stone (OR = 0.33, P < 0.0001). Moreover, SF patients had significantly lower score of Guy score (WMD = -0.64, P < 0.0001), but, S.T.O.N.E. score (WMD = -1.23, P < 0.0001) and a higher score of CROES nomogram (WMD = 29.48, P = 0.003). However, the comparison of area under curves (AUC) of predicting SFR indicated that there was no remarkable difference between three SSSs. Nonetheless, Guy score was the only stone scoring system that predicted complications after PCNL (WMD = -0.29, 95% CI: - 0.57 to - 0.02, P = 0.03). CONCLUSIONS: Our meta-analysis indicated that the three SSSs were equally, feasible and accurate for predicting SFR after PCNL. However, Guy score was the only stone scoring system that predicted complications after PCNL.

C-H Bond Activation for the Synthesis of Heterocyclic Atropisomers Yields Hedgehog Pathway Inhibitors.

Axially chiral 4-arylisoquinolones are endowed with pronounced bioactivity, and methods for their efficient synthesis have gained widespread attention. However, enantioselective synthesis of axially chiral 4-arylisoquinolones by means of C-H activation has not been reported to date. Described here is a rhodium (III)-catalyzed C-H bond activation and annulation for the atroposelective synthesis of axially chiral 4-arylisoquinolones. The method employs chiral cyclopentadienyl ligands embodying a piperidine ring as backbone and yields the atropisomers with good to excellent yields and enantioselectivity. Biological relevance of the 4-arylisoquinolones was demonstrated by their investigation in different cellular assays, leading to the discovery of novel non-SMO (SMO= smoothened) binding Hedgehog pathway inhibitors.

Enantioselective Synthesis of the Spirotropanyl Oxindole Scaffold through Bimetallic Relay Catalysis.

Spirotropanyl oxindole alkaloids like alstonisine and chitosenine show a wide range of bioactivites. We report the first enantioselective synthesis of the spirotropanyl oxindole scaffold by means of a bimetallic relay catalysis strategy. A new class of E-oximino α-diazo ketones was developed for the intramolecular generation of transient azomethine ylides catalyzed by an achiral RhII complex and a subsequent intermolecular 1,3-dipolar cycloaddition catalyzed by a chiral N,N'-dioxide NdIII Lewis acid complex. The enantioselectively catalyzed transformation has broad scope and yields the desired spirotropanyl oxindole cycloadducts in high yields and with very high enantio- and diastereoselectivity.

One-pot synthesis of quaternary carbon centered cyclobutanes via Pd(ii)-catalyzed cascade C(sp3)-H activations.

A novel approach toward quaternary carbon centered cyclobutanes through Pd(ii)-catalyzed sequential intramolecular methylene C-H alkylation and intermolecular methine C-H bond arylation, alkenylation, alkylation, alkynylation, allylation, benzylation or alkoxylation is described. These quaternary carbon centered cyclobutanes could be further diversified through Pd(ii)-catalyzed γ-C(sp3)-H bond activations. The synthetic utility of this novel approach was exemplified by its application to the synthesis of a bioactive small molecule.

[A head-to-head comparison of contemporary indolent prostate cancer screen protocols in Chinese].

OBJECTIVE: To compare the diagnostic accuracy of five internationally used indolent prostate cancer screen protocols in Chinese prostate cancer patients. METHODS: Retrospective analysis was made of the consecutive cohort of 314 patients, from Jan. 2006 to Apr. 2014, who had both prostate biopsy and radical prostatectomy in Peking University First Hospital. The Gleason score≤6, pT2, tumor volume≤0.5 mL, margin negative and lymph nodes negative were defined as indolent prostate cancer. The predictive value of five indolent screen criteria including Epstein, Memorial Sloan-Kettering Cancer Center (MSKCC), Prostate Cancer Research International: Active Surveillance (PRIAS), University of California, San Francisco (UCSF), and University of Miami (UM) were evaluated in Chinese prostate cancer patients. Measures of diagnostic accuracy and areas under the receiver-operating curve (AUC) were calculated for each protocol and compared. RESULTS: A total of 16% (49 cases) of the patients met the inclusion criteria of at least one protocol, including 24 cases in Epstein, 33 cases in MSKCC, 28 cases in PRIAS, 34 cases in UCSF, and 22 cases in UM. Three percent were eligible for all the studied criteria. UCSF and MSKCC protocols had the highest sensitivity and specificity than the others. The Epstein and PRIAS protocols demonstrated acceptable positive predictive value, but the specificity and sensitivity were inefficient. The UM protocol was performed unsatisfiedly on sensitivity, positive predictive value and AUC. A strict limited protocol which contained all the five protocols could not improve the predictive accuracy. CONCLUSION: The UCSF protocol had better diagnostic accuracy than the others, but the results were not satisfied. A further investigation on indolent prostate cancer screening in Chinese patients is needed.

Palladium-catalyzed unactivated ß-methylene C(sp(3))-H bond alkenylation of aliphatic amides and its application in a sequential C(sp(3))-H/C(sp(2))-H bond alkenylation.

A palladium(II)-catalyzed ß-methylene C(sp(3))-H bond alkenylation of acyclic aliphatic amides with alkenyl halides has been developed. Both (E)-olefins and (Z)-olefins can be readily accessed using this method and a possible (Z)/(E)-olefin isomerization pathway is proposed. A solvent effect-promoted sequential C(sp(3))-H bond alkenylation and C(sp(2))-H bond alkenylation was also studied, and can provide a convenient route to novel diene compounds.

An efficient palladium-catalyzed C-H alkoxylation of unactivated methylene and methyl groups with cyclic hypervalent iodine (i(3+) ) oxidants.

All the hype: The title reaction has been developed for the facile synthesis of a variety of complex alkyl ethers. Cyclic hypervalent iodine (I(3+) ) reagents serve as oxidants for this unique CH alkoxylation reaction. The reaction demonstrates excellent reactivity, good functional-group tolerance, and high yields. Q=8-aminoquinoline-derived auxiliary.

A large-scale gene discovery for the red palm weevil Rhynchophorus ferrugineus (Coleoptera: Curculionidae).

The red palm weevil (RPW; Rhynchophorus ferrugineus) is a devastating pest of palms, prevalent in the Middle East as well as many other regions of the world. Here, we report a large-scale de novo complementary DNA (cDNA) sequencing effort that acquired ∼5 million reads and assembled them into 26 765 contigs from 12 libraries made from samples of different RPW developmental stages based on the Roche/454 GS FLX platform. We annotated these contigs based on the publically available known insect genes and the Tribolium castaneum genome assembly. We find that over 80% of coding sequences (CDS) from the RPW contigs have high-identity homologs to known proteins with complete CDS. Gene expression analysis shows that the pupa and larval stages have the highest and lowest expression levels, respectively. In addition, we also identified more than 60 000 single nucleotide polymorphisms and 1 200 simple sequence repeat markers. This study provides the first large-scale cDNA dataset for RPW, a much-needed resource for future molecular studies.