Evaluating the benefits of adjuvant chemotherapy in patients with pancreatic cancer undergoing radical pancreatectomy after neoadjuvant therapy-a systematic review and meta-analysis.

Background: More and more patients with pancreatic cancer (PC) received neoadjuvant therapy (NAT) and then underwent radical pancreatectomy. However, the benefit of adjuvant chemotherapy (AC) for these patients is still controversial. This study is designed to determine the benefits of postoperative AC for patients with PC undergoing NAT and radical resection. Methods: We conducted a comprehensive search of the PubMed, Embase, Web of Science, and Cochrane Library databases, covering the period from their inception until 10 September 2023. Our analysis focused on the assessment of overall survival (OS) and recurrence-free survival (RFS) through meta-analysis. The fixed-effects model and the random-effects model were used to process the data. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were employed to determine the necessary of administering AC for patients with PC who have undergone NAT and radical resection. We retrieved 3,063 search results, of which 3,048 were excluded because of duplication or after applying our inclusion and exclusion criteria. Results: A total of 15 studies with 21,113 patients (7,794 patients in the AC group and 13,319 in the non-AC group) were included, all of which reported OS, and three studies reported disease-free survival (DFS)/tumor-specific survival (CSS)/RFS. The final results showed that AC significantly improved OS and DFS/CSS/RFS in patients with PC who underwent pancreatectomy after NAT [OS: HR = 0.80, 95% CI (0.75∼0.86), P < 0.00001, I2 = 48%; DFS/CSS/RFS: HR = 0.53, 95% CI (0.41~0.69), P < 0.00001, I2 = 0%]. Furthermore, we performed subgroup analyses and demonstrated that AC provided a significant survival benefit for patients with PC after NAT and resection regardless of the tumor size [<2-cm subgroup: HR = 0.72, 95% CI (0.5∼0.94), P = 0.01; ≥2-cm subgroup: HR = 0.79, 95% CI (0.65∼0.96), P = 0.02] and the margin status [R0 subgroup: HR = 0.83, 95% CI (0.77∼0.88), P < 0.00001; R2 subgroup: HR = 0.75, 95% CI (0.61∼0.92), P = 0.007]. AC also benefited the patients with a stage N0 [HR = 0.79, 95% CI (0.74~0.84), P < 0.00001], N1 [HR = 0.78, 95% CI (0.72∼0.85), P < 0.00001], or poorly/undifferentiated tumor [HR = 0.76, 95% CI (0.66∼0.87), P < 0.0001] in survival but not in patients with a stage N2 [HR = 0.69, 95% CI (0.43∼1.09), P = 0.11] or well/moderately differentiated tumor [HR = 0.97, 95% CI (0.66∼1.42), P = 0.87]. Conclusions: Although AC showed survival benefit for patients with PC undergoing radical pancreatectomy after NAT, we still need to consider the lymph node stage and the degree of differentiation of the tumor when we gave AC to a patient. High-quality prospective randomized controlled studies are required to well disclose the value of AC in patients with PC undergoing radical pancreatectomy after NAT. Systematic review registration: https://www.crd.york.ac.uk/prospero/ PROSPERO, identifier CRD42023461365.

Association of screen exposure/sedentary behavior and precocious puberty/early puberty.

Background: In recent years, with the development of society, children's daily exposure to screen time has gradually increased. Screen exposure and sedentary behavior have brought a host of harms to children's lives. The aim of this study was to explore the effects of screen exposure and sedentary behavior on precocious puberty and early development. Methods: This is a cross-sectional study in the school-based population. A total of 3,560 children were recruited from Qufu City, Shandong province using multistage stratified cluster random sampling. All study subjects had a physical examination by professional pediatricians in October 2019, and were investigated with health questionnaires. Precocious puberty is defined as development of secondary sexual signs in boys before 9 years or in girls before 8 years. Screen time was calculated as the average of screen time on weekdays and weekend days, and sedentary time was calculated as the average of sedentary time on weekdays and weekend days. After adjusting for potential confounders, logistic regression was used to examine the association between screen exposure and sedentary behavior and early puberty and precocious puberty. Results: Sedentary time was a risk factor for precocious puberty and early development (OR = 1.428, 95% CI = 1.087-1.876) in girls without adjustment. No significant association was found between screen exposure and early puberty and early development both in girls and boys. Conclusions: Excessive sedentary behavior was associated with an increased risk of early puberty, especially in girls, while there was no significant association between screen exposure and early puberty and early development. In addition, further longitudinal investigations are needed to determine the causal relationship between screen exposure, sedentary behavior and precocious puberty.

Study on seismic response characteristics of living stumps slope based on large-scale shaking table test.

A large-scale shaking table test of a living stump slope with a geometric similarity ratio of 1:7 was designed and completed. The peak acceleration, acceleration amplification factor, and displacement response patterns of living stumps slopes under different types of seismic waves and excitation intensities were obtained. The time-frequency and energy variation characteristics were analyzed using the Hilbert-Huang Transform (HHT). The results showed that: (1) Regardless of the type of seismic wave, the peak acceleration and acceleration amplification factor of the living stumps slope surface are positively correlated with relative height and seismic excitation intensity. When the excitation intensity is ≤ 0.4 g, the acceleration amplification effect is more pronounced; when the excitation intensity is > 0.4 g, the acceleration amplification effect weakens. (2) Under the action of different seismic waves, the peak displacement of slope surface shows amplification effect along the elevation, and increases with the increase of excitation intensity. In addition, the incremental displacement gradually decreases from the toe to the top of the slope, which is expressed as D2 > D3 > D1 > D4 > D5. The peak displacement at the top of the slope is the greatest, but the incremental displacement is the smallest; the peak displacement at the toe of the slope is the smallest, but the incremental displacement is relatively large. (3) Regardless of the type of seismic wave, living stumps slope shows the characteristics of filtering the low-frequency components of the seismic waves and amplifying their high-frequency components. At the same time, the seismic Hilbert energy gradually accumulates along the elevation. PSHEA and PMSA significantly increase with elevation and excitation intensity, and they reach the maximum at the top of the slope. (4) The seismic Hilbert energy is positively correlated with the relative height and excitation intensity, and reaches the maximum at the top of the slope. With the accumulation of seismic Hilbert energy increases, the dynamic response parameters such as peak acceleration, acceleration amplification coefficient and displacement also increase synchronously, reaching the maximum at the top of the slope. The research conclusions can provide an experimental basis for the seismic design of living stumps slopes.

Chitosan-based hydrogel dressings with antibacterial and antioxidant for wound healing.

Bacterial infection and free radical oxidative stress at the wound site could easily cause cascade inflammation and hinder the healing process of the wound. In this study, chitosan-cysteine-gallic acid (CCG) hydrogel with antibacterial and antioxidant properties was synthesized by chitosan (CS), cysteine (Cys), and gallic acid (GA) for a preliminary evaluation of its therapeutic efficacy in a mouse model of full-layer skin defect. In vitro analysis showed that the CCG hydrogel had good antibacterial activity and blood compatibility. In vivo, the CCG hydrogel wound dressings accelerated wound healing, stimulate angiogenesis, increase collagen deposition and anti-inflammatory factor expression. The CCG hydrogel wound dressing is designed to promote the regeneration of damaged skin tissue and is expected to become a potential candidate for clinical treatment.

Laparoscopic enucleation of tumors embedded in the pancreatic head: Safety and feasibility.

BACKGROUND: Surgical treatment for a benign or low-grade malignant tumor in the pancreatic head remains a challenge at present. As an organ-sparing procedure, enucleation is ideal. However, it is still controversial whether laparoscopic enucleation (LapEN) can be safely performed for a pancreatic head tumor, especially a deeply embedded one. METHODS: The cases who underwent LapEN of a pancreatic tumor from January 2014 to September 2022 in our hospital were collected and analyzed. RESULTS: A total of 151 cases were collected. The incidence of pancreatic fistula (PF, grade B) was 21.9 %. No patient developed PF (grade C) or died. Compared with enucleating a tumor in the distal pancreas (N = 98), enucleating a tumor in the pancreatic head (N = 53) showed a longer operation time and a higher incidence of conversion. The cases with a tumor in the pancreatic head were then divided into the group with a deeply embedded tumor (N = 32) and the group with a superficial tumor (N = 21). The embedded group had a smaller tumor size and a higher proportion of insulinoma. There were no statistical differences in the parameters of operation time, blood loss and incidence of complications between the two groups. The outcomes of enucleating a tumor deeply embedded in the proximal and distal pancreas were further analyzed, which indicated no statistical differences in clinical parameters between the two groups. CONCLUSION: LapEN of a tumor in the pancreatic head is feasible and safe, even for a deeply embedded tumor.

Enhancing nitrate removal from small wetlands via regulating bacterial-algal symbiosis with macrophyte coverage.

With increasing land resource constraints, wetlands, as ecological hotspots, are expected to enhance biogeochemical processes to mitigate nitrogen (N) pollution, particularly nitrate-nitrogen (NO3--N). However, the interactions among bacteria, algae, and macrophytes in wetlands, which are crucial for N removal, remain largely unknown. This study explored how macrophyte coverage influences bacterial-algal interactions, shifting from mutualism to inhibition, thereby affecting N removal. Moderate coverage enhanced NO3--N and total nitrogen (TN) removal (P < 0.05), which was correlated with increased microbial abundance (P < 0.05). This may have resulted from moderate algal photosynthesis, reduced physiological stress, and the expansion of ecological niches for microbes. Insufficient coverage promoted algal growth (chlorophyll-a > 31.8 µg·L-1), leading to increased competition for substrates and elevated pH, which further inhibited bacterial activity. Excessive coverage also inhibited bacterial activity by reducing illumination and oxidation-reduction potential. Consequently, insufficient and excessive coverage decreased N removal efficiencies by 2.7-15.7 % (NO3--N) and 3.7-11.1 % (TN) while increasing methane emission potential by 1.4-6.9 times compared with moderate coverage. These findings offer insights into solving NO3--N contamination using near-natural methods and balancing the ecological and practical considerations for small wetlands.

A gas spark switch electrode impact pressure test platform.

The discharge arc of a high-current gas spark switch has a strong mechanical effect on the electrode and adjacent objects. The measurement of this mechanical effect on the electrode plays a very important role in switch design and the theoretical study of spark discharge. However, in traditional stress measurement systems, the spatial electromagnetic interference caused by the discharge and the high electrode voltage affects the measurement accuracy and can even damage the experimental instrument. In this paper, an electrode impact stress measurement system based on PVDF piezoelectric film is designed to measure the electrode stress under a strong spatial electromagnetic field and high voltage. The experimental results show that the system can measure the impact pressure of high-voltage and high-current gas spark switch electrodes. The starting time of the stress measurement waveform shows that the shock to the electrode is formed in the initial stage of current buildup. The measured results clearly show the high magnetic field force component in the electrode impact pressure waveform. The shock waveforms induced by different pulse capacitor values, breakdown voltages, and loads are examined. It is found that the shock stress waveforms applied to the electrodes are affected by the peak value of the current, dI/dt, and the discharge duration.

Strength Recovery of Thermally Damaged High-Performance Concrete during Recuring.

High-performance concrete (HPC) experiences significant degradation in its mechanical properties after fire exposure. While various post-fire curing methods have been proposed to rehabilitate thermally damaged concrete (TDC), the physical and chemical changes occurring during these processes are not well-understood. This study examines the strength and microstructure restoration of HPC through water and water-CO2 cyclic recuring. HPC samples were initially heated to 600 °C and 900 °C, then subjected to water and cyclic recuring. Results indicate that the mechanical performance recovery of thermally damaged HPC is significantly better with cyclic recuring than with water recuring. The compressive strength of HPC samples exposed to 600 °C and 900 °C reached 131.6% and 70.3% of their original strength, respectively, after cyclic recuring. The optimal recuring duration for substantial recovery in thermally damaged HPC was determined to be 18 days. The strength recovery is primarily due to the healing of microcracks and the densification of decomposed cement paste. These findings clarify the physical and chemical processes involved in post-fire curing of HPC, highlighting the potential of water and water-CO2 cyclic recuring in the rehabilitation of TDC.

Reduction of (100)-Faceted CeO2 for Effective Pt Loading.

Although the function and stability of catalysts are known to significantly depend on their dispersion state and support interactions, the mechanism of catalyst loading has not yet been elucidated. To address this gap in knowledge, this study elucidates the mechanism of Pt loading based on a detailed investigation of the interaction between Pt species and localized polarons (Ce3+) associated with oxygen vacancies on CeO2(100) facets. Furthermore, an effective Pt loading method was proposed for achieving high catalytic activity while maintaining the stability. Enhanced dispersibility and stability of Pt were achieved by controlling the ionic interactions between dissolved Pt species and CeO2 surface charges via pH adjustment and reduction pretreatment of the CeO2 support surface. This process resulted in strong interactions between Pt and the CeO2 support. Consequently, the oxygen-carrier performance was improved for CH4 chemical looping reforming reactions. This simple interaction-based loading process enhanced the catalytic performance, allowing the efficient use of noble metals with high performance and small loading amounts.

Comprehensive toxicological, metabolomic, and transcriptomic analysis of the biodegradation and adaptation mechanism by Achromobacter xylosoxidans SL-6 to diuron.

Biodegradation was considered a promising and environmentally friendly method for treating environmental pollution caused by diuron. However, the mechanisms of biodegradation of diuron required further research. In this study, the degradation process of diuron by Achromobacter xylosoxidans SL-6 was systematically investigated. The results suggested that the antioxidant system of strain SL-6 was activated by adding diuron, thereby alleviating their oxidative stress response. In addition, degradation product analysis showed that diuron in strain SL-6 was mainly degraded by urea bridge cleavage, dehalogenation, deamination, and ring opening, and finally cis, cis-muconic acid was generated. The combined analysis of metabolomics and transcriptomics revealed the biodegradation and adaptation mechanism of strain SL-6 to diuron. Metabolomics analysis showed that after the strain SL-6 was exposed to diuron, metabolic pathways such as tricarboxylic acid cycle (cis, cis-muconic acid), glutathione metabolism (oxidized glutathione), and urea cycle (arginine) were reprogrammed in the cells. Furthermore, diuron could induce the production of membrane transport proteins in strain SL-6 cells and overexpress antioxidant enzyme genes, finally ultimately promoting the up-regulation of genes encoding amide hydrolases and dioxygenases, which was revealed by transcriptomics studies. This work enriched the biodegradation mechanism of phenylurea herbicides and provided guidance for the removal of diuron residues in the environment and promoting agriculture sustainable development.

Dual-molecular targeting nanomedicine upregulates synergistic therapeutic efficacy in preclinical hepatoma models.

Advanced hepatocellular carcinoma (HCC) is one of the most challenging cancers because of its heterogeneous and aggressive nature, precluding the use of curative treatments. Sorafenib (SOR) is the first approved molecular targeting agent against the mitogen-activated protein kinase (MAPK) pathway for the noncurative therapy of advanced HCC; yet, any clinically meaningful benefits from the treatment remain modest, and are accompanied by significant side effects. Here, we hypothesized that using a nanomedicine platform to co-deliver SOR with another molecular targeting drug, metformin (MET), could tackle these issues. A micelle self-assembled with amphiphilic polypeptide methoxy poly(ethylene glycol)-block-poly(L-phenylalanine-co-l-glutamic acid) (mPEG-b-P(LP-co-LG)) (PM) was therefore designed for combinational delivery of two molecular targeted drugs, SOR and MET, to hepatomas. Compared with free drugs, the proposed, dual drug-loaded micelle (PM/SOR+MET) enhanced the drugs' half-life in the bloodstream and drug accumulation at the tumor site, thereby inhibiting tumor growth effectively in the preclinical subcutaneous, orthotopic and patient-derived xenograft hepatoma models without causing significant systemic and organ toxicity. Collectively, these findings demonstrate an effective dual-targeting nanomedicine strategy for treating advanced HCC, which may have a translational potential for cancer therapeutics. STATEMENT OF SIGNIFICANCE: Treatment of advanced hepatocellular carcinoma (HCC) remains a formidable challenge due to its aggressive nature and the limitations inherent to current therapies. Despite advancements in molecular targeted therapies, such as Sorafenib (SOR), their modest clinical benefits coupled with significant adverse effects underscore the urgent need for more efficacious and less toxic treatment modalities. Our research presents a new nanomedicine platform that synergistically combines SOR with metformin within a specialized diblock polypeptide micelle, aiming to enhance therapeutic efficacy while reducing systemic toxicity. This innovative approach not only exhibits marked antitumor efficacy across multiple HCC models but also significantly reduces the toxicity associated with current treatments. Our dual-molecular targeting approach unveils a promising nanomedicine strategy for the molecular treatment of advanced HCC, potentially offering more effective and safer treatment alternatives with significant translational potential.

A dual role of ERGIC-localized Rabs in TMED10-mediated unconventional protein secretion.

Cargo translocation across membranes is a crucial aspect of secretion. In conventional secretion signal peptide-equipped proteins enter the endoplasmic reticulum (ER), whereas a subset of cargo lacking signal peptides translocate into the ER-Golgi intermediate compartment (ERGIC) in a process called unconventional protein secretion (UcPS). The regulatory events at the ERGIC in UcPS are unclear. Here we reveal the involvement of ERGIC-localized small GTPases, Rab1 (Rab1A and Rab1B) and Rab2A, in regulating UcPS cargo transport via TMED10 on the ERGIC. Rab1 enhances TMED10 translocator activity, promoting cargo translocation into the ERGIC, whereas Rab2A, in collaboration with KIF5B, regulates ERGIC compartmentalization, establishing a UcPS-specific compartment. This study highlights the pivotal role of ERGIC-localized Rabs in governing cargo translocation and specifying the ERGIC's function in UcPS.

Unravelling the origin of reaction-driven aggregation and fragmentation of atomically dispersed Pt catalyst on ceria support.

Metal-support interaction plays a crucial role in governing the stability and activity of atomically dispersed platinum catalysts on ceria support. The migration and aggregation of platinum atoms during the catalytic reaction leads to the redistribution of active sites. In this study, by utilizing a multimodal characterization scheme, we observed the aggregation of platinum atoms at high temperatures under reverse water gas shift reaction conditions and the subsequent fragmentation of platinum clusters, forming "single atoms" upon cooling. Theoretical simulations of both effects uncovered the roles of carbon monoxide binding on perimeter Pt sites in the clusters and hydrogen coverage in the aggregation and fragmentation mechanisms. This study highlights the complex effects of adsorbate and supports interactions with metal sites in Pt/ceria catalysts that govern their structural transformations under in situ conditions.

De novo transcriptome assembly database for 100 tissues from each of seven species of domestic herbivore.

Domesticated herbivores are an important agricultural resource that play a critical role in global food security, particularly as they can adapt to varied environments, including marginal lands. An understanding of the molecular basis of their biology would contribute to better management and sustainable production. Thus, we conducted transcriptome sequencing of 100 to 105 tissues from two females of each of seven species of herbivore (cattle, sheep, goats, sika deer, horses, donkeys, and rabbits) including two breeds of sheep. The quality of raw and trimmed reads was assessed in terms of base quality, GC content, duplication sequence rate, overrepresented k-mers, and quality score distribution with FastQC. The high-quality filtered RNA-seq raw reads were deposited in a public database which provides approximately 54 billion high-quality paired-end sequencing reads in total, with an average mapping rate of ~93.92%. Transcriptome databases represent valuable resources that can be used to study patterns of gene expression, and pathways that are related to key biological processes, including important economic traits in herbivores.

An Experimental Study on the Mechanical Properties and Microstructure of the Cemented Paste Backfill Made by Coal-Based Solid Wastes and Nanocomposite Fibers under Dry-Wet Cycling.

The mechanical properties and microstructure of the cemented paste backfill (CPB) in dry-wet cycle environments are particularly critical in backfill mining. In this study, coal gangue, fly ash, cement, glass fiber, and nano-SiO2 were used to prepare CPB, and dry-wet cycle tests on CPB specimens with different curing ages were conducted. The compressive, tensile, and shear strength of CPB specimens with different curing ages under different dry-wet cycles were analyzed, and the microstructural damage of the specimens was observed by scanning electron microscopy (SEM). The results show that compared with the specimens without dry-wet cycles, the uniaxial compressive strength, tensile strength, and shear strength of the specimens with a curing age of 7 d after seven dry-wet cycles were the smallest, being reduced by 40.22%, 58.25%, and 66.8%, respectively. After seven dry-wet cycles, the compressive, tensile, and shear strength of the specimens with the curing age of 28 d decreased slightly. The SEM results show that with the increasing number of dry-wet cycles, the internal structure of the specimen becomes more and more loose and fragile, and the damage degree of the structural skeleton gradually increases, leading to the poor mechanical properties of CPB specimens. The number of cracks and pores on the specimen surface is relatively limited after a curing age of 28 d, while the occurrence of internal structural damage within the specimen remains insignificant. Therefore, the dry-wet cycle has an important influence on the both mechanical properties and microstructure of CPB. This study provides a reference for the treatment of coal-based solid waste and facilitates the understanding of the mechanical properties of backfill materials under dry-wet cycling conditions.

Quantitative Detection of Multiple Cardiovascular Biomarkers by an Antibody Microarray-Based Metal-Enhanced Fluorescence Assay.

Accurate detection of multiple cardiovascular biomarkers is crucial for the timely screening of acute coronary syndrome (ACS) and differential diagnosis from acute aortic syndrome (AAS). Herein, an antibody microarray-based metal-enhanced fluorescence assay (AMMEFA) has been developed to quantitatively detect 7 cardiovascular biomarkers through the formation of a sandwich immunoassay on the poly(glycidyl methacrylate-co-2-hydroxyethyl methacrylate)-decorated GNR-modified slide (GNR@P(GMA-HEMA) slide). The AMMEFA exhibits high specificity and sensitivity, the linear ranges span 5 orders of magnitude, and the limits of detection (LODs) of cardiac troponin I (cTnI), heart-type fatty acid binding protein (H-FABP), C-reactive protein (CRP), copeptin, myoglobin, D-Dimer, and N-terminal pro-brain natriuretic peptide (NT-proBNP) reach 0.07, 0.2, 65.7, 0.6, 0.2, 8.3, and 0.3 pg mL-1, respectively. To demonstrate its practicability, the AMMEFA has been applied to quantitatively analyze 7 cardiovascular biomarkers in 140 clinical plasma samples. In addition, the expression levels of cardiovascular biomarkers were analyzed by the least absolute shrinkage and selector operator (LASSO) regression, and the area under receiver operator characteristic curves (AUCs) of healthy donors (HDs), ACS patients, and AAS patients are 0.99, 0.98, and 0.97, respectively.

Distinct Changes in Metabolic Profile and Sensory Quality with Different Varieties of Chrysanthemum (Juhua) Tea Measured by LC-MS-Based Untargeted Metabolomics and Electronic Tongue.

Chrysanthemum tea, a typical health tea with the same origin as medicine and food, is famous for its unique health benefits and flavor. The taste and sensory quality of chrysanthemum (Juhua) tea are mainly determined by secondary metabolites. Therefore, the present research adopted untargeted metabolomics combined with an electronic tongue system to analyze the correlation between the metabolite profiles and taste characteristics of different varieties of chrysanthemum tea. The results of sensory evaluation showed that there were significant differences in the sensory qualities of five different varieties of chrysanthemum tea, especially bitterness and astringency. The results of principal component analysis (PCA) indicated that there were significant metabolic differences among the five chrysanthemum teas. A total of 1775 metabolites were identified by using untargeted metabolomics based on UPLC-Q-TOF/MS analysis. According to the variable importance in projection (VIP) values of the orthogonal projections to latent structures discriminant analysis (OPLS-DA), 143 VIP metabolites were found to be responsible for metabolic changes between Huangju and Jinsi Huangju tea; among them, 13 metabolites were identified as the key metabolites of the differences in sensory quality between them. Kaempferol, luteolin, genistein, and some quinic acid derivatives were correlated with the "astringency" attributes. In contrast, l-(-)-3 phenyllactic acid and L-malic acid were found to be responsible for the "bitterness" and "umami" attributes in chrysanthemum tea. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the flavonoid and flavonol biosynthesis pathways had important effects on the sensory quality of chrysanthemum tea. These findings provide the theoretical basis for understanding the characteristic metabolites that contribute to the distinctive sensory qualities of chrysanthemum tea.

Multi-response Regression for Block-missing Multi-modal Data without Imputation.

Multi-modal data are prevalent in many scientific fields. In this study, we consider the parameter estimation and variable selection for a multi-response regression using block-missing multi-modal data. Our method allows the dimensions of both the responses and the predictors to be large, and the responses to be incomplete and correlated, a common practical problem in high-dimensional settings. Our proposed method uses two steps to make a prediction from a multi-response linear regression model with block-missing multi-modal predictors. In the first step, without imputing missing data, we use all available data to estimate the covariance matrix of the predictors and the cross-covariance matrix between the predictors and the responses. In the second step, we use these matrices and a penalized method to simultaneously estimate the precision matrix of the response vector, given the predictors, and the sparse regression parameter matrix. Lastly, we demonstrate the effectiveness of the proposed method using theoretical studies, simulated examples, and an analysis of a multi-modal imaging data set from the Alzheimer's Disease Neuroimaging Initiative.

Asymmetric Total Syntheses of ent-Stachybotrin C and Its Congener.

The asymmetric total syntheses of ent-stachybotrin C and its congener have been accomplished through a convergent approach in the longest linear sequence of 12 steps from commercially available materials, respectively. Noteworthy transformation of the synthesis involved a cascade Knoevenagel condensation/Hantzsch ester reduction/epoxide ring-opening/transetherification to construct the core pyran ring with two adjacent stereocenters.