Learn to optimize-a brief overview.

Most optimization problems of practical significance are typically solved by highly configurable parameterized algorithms. To achieve the best performance on a problem instance, a trial-and-error configuration process is required, which is very costly and even prohibitive for problems that are already computationally intensive, e.g. optimization problems associated with machine learning tasks. In the past decades, many studies have been conducted to accelerate the tedious configuration process by learning from a set of training instances. This article refers to these studies as learn to optimize and reviews the progress achieved.

Data-driven inverse design of flexible pressure sensors.

Artificial skins or flexible pressure sensors that mimic human cutaneous mechanoreceptors transduce tactile stimuli to quantitative electrical signals. Conventional trial-and-error designs for such devices follow a forward structure-to-property routine, which is usually time-consuming and determines one possible solution in one run. Data-driven inverse design can precisely target desired functions while showing far higher productivity, however, it is still absent for flexible pressure sensors because of the difficulties in acquiring a large amount of data. Here, we report a property-to-structure inverse design of flexible pressure sensors, exhibiting a significantly greater efficiency than the conventional routine. We use a reduced-order model that analytically constrains the design scope and an iterative "jumping-selection" method together with a surrogate model that enhances data screening. As an exemplary scenario, hundreds of solutions that overcome the intrinsic signal saturation have been predicted by the inverse method, validating for a variety of material systems. The success in property design on multiple indicators demonstrates that the proposed inverse design is an efficient and powerful tool to target multifarious applications of flexible pressure sensors, which can potentially advance the fields of intelligent robots, advanced healthcare, and human-machine interfaces.

Exploring the action mechanism of Gegensan in the treatment of alcoholic liver disease based on network pharmacology and bioinformatics.

Gegensan (GGS) has been reported for the treatment of alcoholic liver disease (ALD), but its therapeutic mechanism is still unclear. This paper aims to determine the therapeutic mechanism and targets of action of GGS on alcoholic liver disease utilizing network pharmacology and bioinformatics. The active ingredients in GGS were screened in the literature and databases, and common targets of ALD were then obtained from public databases to construct the network diagram of traditional Chinese medicine-active ingredient targets. Based on the common targets, Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to find target enrichment pathways, and the core targets were screened out by combining differential analysis and protein-protein interaction network analysis. Molecular docking was performed to verify the binding effect between the core targets and the corresponding active ingredients. ALD and GGS have 84 common targets, corresponding to 91 active ingredients. After subsequent differential analysis and protein-protein interaction network analysis, 10 core targets were identified. Gene Ontology and KEGG enrichment analyses showed that the main BPs corresponding to the common targets included the response to lipopolysaccharide, inflammatory response, etc. The KEGG pathways involved in the regulation of the common targets included the lipid-atherosclerosis pathway and the alcoholic liver disease pathway, etc. Further molecular docking showed that the core targets CYP1A1, CYP1A2, CXCL8, ADH1C, MMP1, SERPINE1, COL1A1, APOB, MMP1, and their corresponding 4 active ingredients, Naringenin, Kaempferol, Quercetin, and Stigmasterol, have a greater docking potential. The above results suggest that GGS can regulate lipid metabolism and inflammatory response in the ALD process, and alleviate the lipid accumulation and oxidative stress caused by ethanol. This study analyzed the core targets and mechanisms of action of GGS on ALD, which provides certain theoretical support for the further development of GGS in the treatment of ALD, and provides a reference for the subsequent research on the treatment of ALD.

Cold exposure-induced plasma exosomes impair bone mass by inhibiting autophagy.

Recently, environmental temperature has been shown to regulate bone homeostasis. However, the mechanisms by which cold exposure affects bone mass remain unclear. In our present study, we observed that exposure to cold temperature (CT) decreased bone mass and quality in mice. Furthermore, a transplant of exosomes derived from the plasma of mice exposed to cold temperature (CT-EXO) can also impair the osteogenic differentiation of BMSCs and decrease bone mass by inhibiting autophagic activity. Rapamycin, a potent inducer of autophagy, can reverse cold exposure or CT-EXO-induced bone loss. Microarray sequencing revealed that cold exposure increases the miR-25-3p level in CT-EXO. Mechanistic studies showed that miR-25-3p can inhibit the osteogenic differentiation and autophagic activity of BMSCs. It is shown that inhibition of exosomes release or downregulation of miR-25-3p level can suppress CT-induced bone loss. This study identifies that CT-EXO mediates CT-induced osteoporotic effects through miR-25-3p by inhibiting autophagy via targeting SATB2, presenting a novel mechanism underlying the effect of cold temperature on bone mass.

Chance-Constrained Multiple-Choice Knapsack Problem: Model, Algorithms, and Applications.

The multiple-choice knapsack problem (MCKP) is a classic NP-hard combinatorial optimization problem. Motivated by several significant real-world applications, this work investigates a novel variant of MCKP called the chance-constrained MCKP (CCMCKP), where item weights are random variables. In particular, we focus on the practical scenario of CCMCKP, in which the probability distributions of random weights are unknown and only sample data is available. We first present the problem formulation of CCMCKP and then establish the two benchmark sets. The first set contains synthetic instances, while the second set is designed to simulate a real-world application scenario of a telecommunication company. To solve CCMCKP, we propose a data-driven adaptive local search (DDALS) algorithm. Compared to existing stochastic optimization and distributionally robust optimization methods, the main novelty of DDALS lies in its data-driven solution evaluation approach, which does not make any assumptions about the underlying distributions and is highly effective even when faced with a high intensity of the chance constraint and a limited amount of sample data. Experimental results demonstrate the superiority of DDALS over the baselines on both the benchmarks. Finally, DDALS can serve as the baseline for future research, and the benchmark sets are open-sourced to further promote research on this challenging problem.

Photoredox Ring Opening 1,2-Alkylarylation of Alkenes with Sulfonium Salts Toward Thioether-Substituted Oxindoles.

A novel strategy for the difunctionalization of electron-deficient alkenes with aryl sulfonium salts to access remote sulfur-containing oxindole derivatives by using in situ-formed copper(I)-based complexes as a photoredox catalyst is presented. This method enables the generation of the C(sp3)-centered radicals through site selective cleavage of the C-S bond of aryl sulfonium salts under mild conditions. Moreover, the oxidation reactions of desired products provide a new strategy for the preparation of sulfoxide or sulfone-containing compounds. Importantly, this approach can be easily applied to late-stage modification of pharmaceuticals molecules.

Automated algorithm aided capacity and confidence boost in surgical decision-making training for inferior clivus.

Objective: To assess the impact of automated algorithms on the trainees' decision-making capacity and confidence for individualized surgical planning. Methods: At Chinese PLA General Hospital, trainees were enrolled to undergo decision-making capacity and confidence training through three alternative visual tasks of the inferior clivus model formed from an automated algorithm and given consecutively in three exemplars. The rationale of automated decision-making was used to instruct each trainee. Results: Following automated decision-making calculation in 50 skull base models, we screened out three optimal plans, infra-tubercle approach (ITA), trans-tubercle approach (TTA), and supra-tubercle approach (STA) for 41 (82.00%), 8 (16.00%), and 1 (2.00%) subject, respectively. From September 1, 2023, through November 17, 2023, 62 trainees (median age [range]: 27 [26-28]; 28 [45.16%] female; 25 [40.32%] neurosurgeons) made a decision among the three plans for the three typical models (ITA, TTA, and STA exemplars). The confidence ratings had fine test-retest reliability (Spearman's rho: 0.979; 95% CI: 0.970 to 0.988) and criterion validity with time spent (Spearman's rho: -0.954; 95%CI: -0.963 to -0.945). Following instruction of automated decision-making, time spent (initial test: 24.02 vs. 7.13 in ITA; 30.24 vs. 7.06 in TTA; 34.21 vs. 12.82 in STA) and total hits (initial test: 30 vs. 16 in ITA; 37 vs. 17 in TTA; 42 vs. 28 in STA) reduced significantly; confidence ratings (initial test: 2 vs. 4 in ITA; 2 vs. 4 in TTA; 1 vs. 3 in STA) increased correspondingly. Statistically significant differences (P < 0.05) were observed for the above comparisons. Conclusions: The education tool generated by automated decision-making considers surgical freedom and injury risk for the individualized risk-benefit assessment, which may provide explicit information to increase trainees' decision-making capacity and confidence.

Electrochemical Oxidative (4 + 2) Cyclization of Anilines and o-Phenylenediamines for the Synthesis of Phenazines.

Phenazines, crucial constituents of nitrogen-containing heterocycles, widely exist in functional compounds. Herein, we report an anodic oxidative (4 + 2) cyclization between anilines and o-phenylenediamines for the uniform construction of phenazines in a simple undivided cell. Dual C-H amination followed by oxidation represents an outstanding step and atom efficiency. A sequence of phenazines is produced with excellent functional group tolerance at room temperature.

Electro-oxidative three-component cascade coupling of isocyanides with elemental sulfur and amines for the synthesis of 2-aminobenzothiazoles.

2-Aminobenzothiazoles are commonly encountered in various functional compounds. Herein, we disclose an electro-oxidative three-component reaction for the effective synthesis of 2-aminobenzothiazoles under mild conditions, utilizing non-toxic and abundant elemental sulfur as the sulfur source. Both aliphatic amines and aryl amines demonstrate good compatibility at room temperature, highlighting the broad functional group tolerance of this approach. Additionally, elemental selenium demonstrated reactivities comparable to those of elemental sulfur.

Regioselective synthesis of N-containing polycyclic compounds via radical annulation cyclization of 1,7-dienes with aldehydes.

A convenient method for oxidant-promoted radical cascade acylation or decarbonylative alkylation of 1,7-dienes with aldehydes has been established. This method allows for the rapid construction of N-containing polycyclic skeletons in a highly regio- and stereoselective manner. This transformation provides a simple and efficient method for the preparation of a range of tetrahydro-6H-indeno[2,1-c]quinolinone derivatives by sequential formation of three new carbon-carbon bonds. Additionally, this radical cascade cyclization can selectively convert aldehydes into aroyl/primary aliphatic acyl radicals and secondary or tertiary alkyl radicals.

Assessment of causal association between the socio-economic status and osteoporosis and fractures: a bidirectional Mendelian randomization study in European population.

BACKGROUND: The relationship between socio-economic status and bone-related diseases is attracting increasing attention. Therefore, a bidirectional Mendelian randomization (MR) analysis was performed in this study. METHODS: Genetic data on factors associated with socio-economic status (average total household income before tax, years of schooling completed and Townsend Deprivation Index at recruitment), femoral neck bone mineral density (FN-BMD), heel bone mineral density (eBMD), osteoporosis, and five different sites of fracture (spine, femur, lower leg-ankle, foot, and wrist-hand fractures) were derived from genome-wide association summary statistics of European ancestry. The inverse variance weighted method was employed to obtain the causal estimates, complemented by alternative MR techniques, including MR-Egger, weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO). Furthermore, sensitivity analyses, and multivariable MR was performed to enhance the robustness of our findings. RESULTS: A higher educational attainment was associated with an increased level of eBMD (beta:0.06, 95% CI:0.01-0.10, P = 7.24 × 10-3), and decreased risk of osteoporosis (OR:0.78, 95% CI:0.65-0.94, P = 8.49 × 10-3), spine fracture (OR:0.76, 95% CI:0.66-0.88, P = 2.94 × 10-4), femur fracture (OR:0.78, 95% CI:0.67-0.91, P = 1.33 × 10-3), lower leg-ankle fracture (OR:0.79, 95% CI:0.70-0.88, P = 2.05 × 10-5), foot fracture (OR:0.78, 95% CI:0.66-0.93, P = 5.92 × 10-3) and wrist-hand fracture (OR:0.83, 95% CI:0.73-0.95, P = 7.15 × 10-3). Further, material deprivation seemed to harm the spine fracture (OR:2.63, 95% CI:1.43-4.85, P = 1.91 × 10-3). A higher level of FN-BMD positively affected increased household income (beta:0.03, 95% CI:0.01-0.04, P = 6.78 × 10-3). All these estimates were adjusted for body mass index (BMI), type 2 diabetes, smoking initiation, and frequency of alcohol intake. CONCLUSIONS: The Mendelian randomization analyses show that higher educational levels is associated with higher eBMD, reduced risk of osteoporosis and fractures, while material deprivation is positively related to spine fracture. Enhanced FN-BMD correlates with increased household income. These findings offer valuable insights into the formulation of health guidelines and policy development.

We conducted stratified analyses to explore the causal links between socio-economic status and osteoporosis and various fractures and observed that education significantly reduced risk of osteoporosis and lower eBMD. It also lowered the risks of fractures of spine, femur, lower leg-ankle, foot, and wrist-hand, while material deprivation exhibited positive associations with spine fracture risk. Bidirectional MR analysis showed that an elevated score of FN-BMD was associated with a higher income level. Our study shows the importance of conducting routine BMD estimations and osteoporosis screening, to enhance knowledge and awareness among individuals to promote bone health and prevent fractures.

Exploiting halide perovskites for heavy metal ion detection.

Heavy metal ions such as mercury (Hg), copper (Cu), and cadmium (Cd) pose significant threats to ecosystems and human health due to their toxicity and bioaccumulation potential. With growing environmental concerns over heavy metal ion pollution, there is an urgent need to develop efficient detection methods for safeguarding public health and the environment. Various materials, including polymers, nanomaterials, and porous substances, have been used for heavy metal ion detection and have shown promising performance for different scenarios. However, each of these materials has certain limitations as probes. Metal halide perovskites (MHPs), known for their exceptional optoelectronic properties and high structural and chemical tunability, have gained great attention in applications such as photovoltaics and LEDs. Yet, their potential as metal ion probes remains rarely explored. This review assesses MHPs as prospective materials for heavy metal ion detection, taking their structure, chemical properties, and responses to external stimuli into consideration. Three key detection mechanisms-cation exchange (CE), electron transfer (ET), and fluorescence resonance energy transfer (FRET), are explored to understand how metal ions trigger fluorescence changes on perovskites, enabling their detection. Finally, current avenues of developing perovskite probes are discussed, which include exploration of lead-free perovskites to mitigate environmental concerns arising from lead leakage and the pursuit of achieving high-sensitivity and stable detection in aqueous media, summarizing the existing and promising strategies in this field.

Oxidant-Assisted Sulfonylation/Cyclization Cascade Synthesis of Alkylsulfonylated Oxindoles via the Insertion of SO2.

An oxidant-assisted tandem sulfonylation/cyclization of electron-deficient alkenes with 4-alkyl-substituted Hantzsch esters and Na2S2O5 for the preparation of 3-alkylsulfonylated oxindoles under mild conditions in the absence of a photocatalyst and transition metal catalyst is established. The mechanism studies show that the alkyl radicals, which come from the cleavage of the C-C bond in 4-substituted Hantzsch esters under oxidant conditions, subsequently undergo the in situ insertion of sulfur dioxide to generate the crucial alkylsulfonyl radical intermediates. This three-component reaction provides an efficient and facile route for the construction of alkylsulfonylated oxindoles and avoids the use of highly toxic alkylsulfonyl chlorides or alkylsulfonyl hydrazines as alkylsulfonyl sources.

Potential Role of MAP3K14 in Hepatocellular Carcinoma: A Study Based on Comprehensive Bioinformatical Analysis and Validation.

According to reports, MAP3K14 is considered an oncogene and is aberrantly expressed in various types of tumor cells. Its abnormal expression is closely associated with the occurrence and progression of various cancers. MAP3K14 also plays a significant role in the development of non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma and its connection to tumor stem cells. The prognostic value of MAP3K14 in HCC, as well as its potential functions and roles, requires further elucidation. We evaluated the potential role of MAP3K14 in HCC based on data mining from a range of public databases. The bioinformatics analysis of TCGA, GEO, TIMER, cBioportal, Kaplan-Meier plotter, MethSurv, ENCORI and CellMiner databases was carried out. The expression of MAP3K14 protein in HCC was detected by immunohistochemical method. The mRNA and protein expression levels of MAP3K14 in tumor tissues were higher than those in normal tissues (p < 0.05). The expression of MAP3K14 was correlated with Pathologic T stage (p=0.026), Pathologic stage (p=0.032), Tumor status (p=0.024) and AFP (p=0.002). HCC patients with high expression of MAP3K14 had poor overall survival (OS), progression free survival (PFS) and recurrence free survival (RFS). Multivariate Cox regression analysis showed that the Pathologic stage (p < 0.001) and MAP3K14 expression levels (p < 0.05) is an independent prognostic factor affecting the survival of patients with liver cancer. GO/KEGG analysis suggested that key biological processes (PI3K-Akt signaling pathway) may be the mechanism promoting HCC development. In addition, MAP3K14 was significantly correlated with the infiltrating levels of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells (p < 0.05). MAP3K14 is up-regulated in HCC and is closely related to the prognosis of HCC patients. MAP3K14 may serve as a potential biomarker for poor prognosis of HCC.

[Coordinated Control of Carbon Emission Reduction and Air Quality Improvement in the Industrial Sector in Hunan Province].

Climate warming and air pollution are the main environmental problems in China. This study used China's Carbon Accounting Database, energy economic model, and air quality model to analyze the potential carbon emission peaking path and synergistic air quality improvement gain in the industrial sector in Hunan Province. Based on China's Carbon Accounting Database and the local industry/energy statistical yearbooks in Hunan, the total CO2 emissions in Hunan Province in 2019 were 310.6 Mt, of which the industrial sector accounted for over 70% of the emissions, mainly from the production and supply of electricity, steam, and heat; the production of non-metallic minerals; and the smelting and pressing of ferrous metals. Three potential industrial carbon emission peaking scenarios were analyzed using the LEAP energy economic model, including the business-as-usual scenario (peaking by 2030), moderate emission reduction scenario (peaking by 2028), and aggressive emission reduction scenario (peaking by 2025), by employing different economic growth rates, energy technology progress, and energy structures of the industrial sector. Furthermore, by combining the anthropogenic air pollutant emission inventory and the regional air quality model WRF-Chem, we analyzed the air quality improvement associated with various carbon emission peak paths. The results showed that the annual mean concentrations of major air pollutants had decreased in the three scenarios, especially in the Chang-Zhu-Tan Region. The aggressive emission reduction scenario was the most effective scenario, followed by the moderate emission reduction scenario and the business-as-usual scenario. Manufacturing was the sector with the most significant synergistic effect of pollution and carbon reduction. When carbon emission peaks were achieved, the annual average concentrations of PM2.5 and PM10 in Hunan Province could be synergistically reduced by 0.6-1.8 µg·m-3 and 1.8-8.9 µg·m-3, respectively. Our findings offer important insights into carbon emission peaking and can provide useful information for potential mitigation actions.

Photoredox-Catalyzed Alkylarylation of N-Aryl Bicyclobutyl Amides with α-Carbonyl Alkyl Bromides: Access to 3-Spirocyclobutyl Oxindoles.

A visible-light-induced radical alkylarylation of N-aryl bicyclobutyl amides with α-carbonyl alkyl bromides for the synthesis of functionalized 3-spirocyclobutyl oxindoles is described in which ß-selective radical addition of the alkyl radical to N-aryl bicyclobutyl amides forms a key radical intermediate followed by interception with intrinsic arene functional group. This approach can be applicable to a wide range of α-carbonyl alkyl bromides, including primary, secondary, and tertiary α-bromoalkyl esters, ketones, nitriles, and nitro compounds.

Comparison of Aroma Compounds and Sensory Characteristics between Two Different Types of Rice-Based Baijiu.

Rice-based Baijiu has gained popularity in the Chinese market. Qingya-flavored Baijiu, a variant of Xiaoqu-fermented Baijiu, employs rice as its primary raw material, with an improved production process compared to traditional rice-flavored Baijiu. We comprehensively characterized and compared the aroma profiles of these two rice-based Baijiu types using static sensory experiments (QDA, quantitative descriptive analysis) and dynamic sensory experiments (TDS, temporal dominance of sensations). Qingya-flavored Baijiu exhibited pronounced plant, oily, and roasted aromas, while traditional rice-flavored Baijiu displayed more prominent fruity, floral, and sour notes. Utilizing GC-O-MS (gas chromatography-olfactometry-mass spectrometry) and multi-method quantification, we qualitatively and quantitatively analyzed 61 key aroma compounds, identifying 22 compounds with significant aroma contributions based on odor activity values (OAVs). Statistical analyses, combining sensory and chemical results, were conducted to predict important aroma compounds responsible for the aroma differences between the two Baijiu types. Aroma Recombination and Omission experiments showed that seven compounds play key roles in the aroma of Qingya-flavored Baijiu, including (2E,4E)-Deca-2,4-dienal, linalool, apricolin, ethyl acetate, ethyl isobutyrate, ethyl caprylate, and ethyl isovalerate.

Recent Advances in the Application of P(III)-Nucleophiles to Create New P-C Bonds through Michaelis-Arbuzov-Type Rearrangement.

Organophosphorus compounds have long been considered valuable in both organic synthesis and life science. P(III)-nucleophiles, such as phosphites, phosphonites, and diaryl/alkyl phosphines, are particularly noteworthy as phosphorylation reagents for their ability to form new P-C bonds, producing more stable, ecofriendly, and cost-effective organophosphorus compounds. These nucleophiles follow similar phosphorylation routes as in the functionalization of P-H bonds and P-OH bonds. Activation can occur through photocatalytic, electrocatalytic, or thermo-driven reactions, often in coordination with a Michaelis-Arbuzov-trpe rearrangement process, to produce the desired products. As such, this review offers a thorough overview of the phosphorylated transformation and potential mechanisms of P(III)-nucleophiles, specifically focusing on developments since 2010. Notably, this review may provide researchers with valuable insights into designing and synthesizing functionalized organophosphorus compounds from P(III)-nucleophiles, guiding future advancements in both research and practical applications.

Sustained AhR activity programs memory fate of early effector CD8+ T cells.

Identification of mechanisms that program early effector T cells to either terminal effector T (Teff) or memory T (Tm) cells has important implications for protective immunity against infections and cancers. Here, we show that the cytosolic transcription factor aryl hydrocarbon receptor (AhR) is used by early Teff cells to program memory fate. Upon antigen engagement, AhR is rapidly up-regulated via reactive oxygen species signaling in early CD8+ Teff cells, which does not affect the effector response, but is required for memory formation. Mechanistically, activated CD8+ T cells up-regulate HIF-1α to compete with AhR for HIF-1ß, leading to the loss of AhR activity in HIF-1αhigh short-lived effector cells, but sustained in HIF-1αlow memory precursor effector cells (MPECs) with the help of autocrine IL-2. AhR then licenses CD8+ MPECs in a quiescent state for memory formation. These findings partially resolve the long-standing issue of how Teff cells are regulated to differentiate into memory cells.