UCHL5 promotes hepatocellular carcinoma progression by promoting glycolysis through activating Wnt/ß-catenin pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) is highly malignant with a dismal prognosis, although the available therapies are insufficient. No efficient ubiquitinase has been identified as a therapeutic target for HCC despite the complicating role that of proteins ubiquitination plays in the malignant development of HCC. METHODS: The expression of ubiquitin carboxyl terminal hydrolase L5 (UCHL5) in HCC tumor tissue and adjacent normal tissue was determined using the cancer genome atlas (TCGA) database and was validated using real-time quantitative polymerase chain reaction (RT-qRCR), Western blot and immunohistochemistry (IHC), and the relation of UCHL5 with patient clinical prognosis was explored. The expression of UCHL5 was knocked down and validated, and the effect of UCHL5 on the biological course of HCC was explored using cellular assays. To clarify the molecular mechanism of action of UCHL5 affecting HCC, expression studies of Adenosine triphosphate adenosine triphosphate (ATP), extracellular acidification (ECAR), and glycolysis-related enzymes were performed. The effects of UCHL5 on ß-catenin ubiquitination and Wnt signaling pathways were explored in depth and validated using cellular functionalities. Validation was also performed in vivo. RESULTS: In the course of this investigation, we discovered that UCHL5 was strongly expressed in HCC at both cellular and tissue levels. The prognosis of patients with high UCHL5 expression is considerably worse than that of those with low UCHL5 expression. UCHL5 has been shown to increase the degree of glycolysis in HCC cells with the impact of stimulating the proliferation and metastasis of HCC cells in both in vivo and in vitro. UCHL5 downregulates its degree of ubiquitination by binding to ß-catenin, which activates the Wnt/ß-catenin pathway and accelerates HCC cell glycolysis. Thereby promoting the growth of the HCC. CONCLUSIONS: In summary, we have demonstrated for the first time that UCHL5 is a target of HCC and promotes the progression of hepatocellular carcinoma by promoting glycolysis through the activation of the Wnt/ß-catenin pathway. UCHL5 may thus serve as a novel prognostic marker and therapeutic target for the treatment of HCC.

Neurobrucellosis: laboratory features, clinical characteristics, antibiotic treatment, and clinical outcomes of 21 patients.

BACKGROUND: Neurobrucellosis (NB) is a rare and serious complication of brucellosis. Its clinical manifestations vary, with no obvious specificity. At present, there is no clear clinical diagnosis or treatment for reference. In this study, we retrospectively analyzed the clinical data for 21 patients with NB to provide reference data for its further study. METHODS: We analyzed the epidemiological and clinical manifestations, laboratory tests, imaging examinations, cerebrospinal fluid, and treatment plans of 21 patients diagnosed with NB in the Department of Neurology, Xuanwu Hospital, Capital Medical University Beijing, China. RESULTS: The ages of the patients ranged from 15 to 60 years old (mean age 40.1 ± 13.33 years), the male: female ratio was 4.25:1. Thirteen patients had a history of animal (sheep, cattle) contact, three had no history of animal contact, and the contact status of four was unknown. Brucella can invade various systems of the body and show multi-system symptoms, the main general manifestations were fever (66.67%), fatigue (57.14%) and functional urination or defecation disturbance (42.86%). The main nervous system manifestations were limb weakness (52.38%) and hearing loss (47.62%).The main positive signs of the nervous system included positive pathological signs (71.43%), sensory abnormalities (52.38%), limb paralysis (42.86%). Nervous system lesions mainly included spinal cord damage (66.67%), cranial nerve involvement (61.90%), central demyelination (28.57%) and meningitis (28.57%). In patients with cranial nerve involvement, 69.23% of auditory nerve, 15.38% of optic nerve and 15.38% of oculomotor nerve were involved. The blood of eight patients was cultured for Brucella, and three (37.5%) cultures were positive and five (63.5%) negative. The cerebrospinal fluid (CSF) of eight patients was cultured for Brucella, and two (25.00%) cultures were positive and six (75.00%) negative. Nineteen of the patients underwent a serum agglutination test (SAT), 18 (94.74%) of whom were positive and one (5.26%) of whom were negative. A biochemical analysis of the CSF was performed in 21 patients, and the results were all abnormal. Nineteen patients underwent magnetic resonance imaging (MRI). Twenty-one patients were treated with doxycycline and/or rifampicin, combined with ceftriaxone, quinolone, aminoglycoside, or minocycline. After hospitalization, 15 patients improved (71.43%), two patients did not recover, and the status of four patients was unknown. CONCLUSIONS: The clinical manifestations, CSF parameters, and neurological imaging data for patients with NB show no significant specificity or correlations. When patients with unexplained neurological symptoms accompanied by fever, fatigue, and other systemic manifestations in a brucellosis epidemic area or with a history of contact with cattle, sheep, animals, or raw food are encountered in clinical practice, the possibility of NB should be considered. Treatment is based on the principles of an early, combined, and long course of treatment, and the general prognosis is good.

Preparation of NIR-II Polymer Nanoprobe Through Twisted Intramolecular Charge Transfer and Förster Resonance Energy Transfer of NIR-I Dye.

Near-infrared-II (NIR-II) fluorescence imaging is pivotal in biomedical research. Organic probes exhibit high potential in clinical translation, due to advantages such as precise structure design, low toxicity, and post-modifications convenience. In related preparation, enhancement of NIR-II tail emission from NIR-I dyes is an efficient method. In particular, the promotion of twisted intramolecular charge transfer (TICT) of relevant NIR-I dyes is a convenient protocol. However, present TICT-type probes still show disadvantages in relatively low emission, large particle sizes, or limited choice of NIR-I dyes, etc. Herein, the synthesis of stable small-sized polymer NIR-II fluoroprobes (e.g., 7.2 nm), integrating TICT and Förster resonance energy transfer process to synergistically enhance the NIR-II emission is reported. Strong enhanced emissions can be obtained from various NIR-I dyes and lanthanide elements (e.g., twelvefold at 1250 nm from Nd-DTPA/IR-808 sample). The fluorophore provides high-resolution angiography, with high-contrast imaging on middle cerebral artery occlusion model mice for distinguishing occlusion. The fluorophore can be rapidly excreted from the kidney (urine ≈65% within 4 h) in normal mice and exhibits long-term renal retention on acute kidney injury mice, showing potential applications in the prognosis of kidney diseases. This development provides an effective strategy to design and synthesize effective NIR-II fluoroprobes.

Study on Anomalous Hall Effect and Spin-Orbit Torque Effect of TbCo-Based Multilayer Films.

The anomalous Hall effect and spin-orbit torque of TbCo-based multilayer films have been methodically studied in recent years. Many properties of the films can be obtained by the anomalous Hall resistance loops of the samples. We report on the effects of a structure composed of two heavy metals as the buffer layers on the anomalous Hall resistance loops of TbCo-based multilayers at different temperatures. The results showed that the coercivity increases dramatically with decreasing temperature, and the samples without perpendicular magnetic anisotropy at room temperature showed perpendicular magnetic anisotropy at low temperatures. We quantified the spin-orbit torque efficiency and Dzyaloshinskii-Moriya interaction effective field size of the films W/Pt/TbCo/Pt at room temperature by measuring the loop shift of anomalous Hall resistance. The results showed that the study of anomalous Hall resistance loops plays an important role in the study of spintronics, which can not only show the basic properties of the sample, but can also obtain other information about the sample through the shift of the loops.

Epigenetic silencing schlafen-11 sensitizes esophageal cancer to ATM inhibitor.

BACKGROUND: Targeting DNA damage response (DDR) pathway is a cutting-edge strategy. It has been reported that Schlafen-11 (SLFN11) contributes to increase chemosensitivity by participating in DDR. However, the detailed mechanism is unclear. AIM: To investigate the role of SLFN11 in DDR and the application of synthetic lethal in esophageal cancer with SLFN11 defects. METHODS: To reach the purpose, eight esophageal squamous carcinoma cell lines, 142 esophageal dysplasia (ED) and 1007 primary esophageal squamous cell carcinoma (ESCC) samples and various techniques were utilized, including methylation-specific polymerase chain reaction, CRISPR/Cas9 technique, Western blot, colony formation assay, and xenograft mouse model. RESULTS: Methylation of SLFN11 was exhibited in 9.15% of (13/142) ED and 25.62% of primary (258/1007) ESCC cases, and its expression was regulated by promoter region methylation. SLFN11 methylation was significantly associated with tumor differentiation and tumor size (both P < 0.05). However, no significant associations were observed between promoter region methylation and age, gender, smoking, alcohol consumption, TNM stage, or lymph node metastasis. Utilizing DNA damaged model induced by low dose cisplatin, SLFN11 was found to activate non-homologous end-joining and ATR/CHK1 signaling pathways, while inhibiting the ATM/CHK2 signaling pathway. Epigenetic silencing of SLFN11 was found to sensitize the ESCC cells to ATM inhibitor (AZD0156), both in vitro and in vivo. CONCLUSION: SLFN11 is frequently methylated in human ESCC. Methylation of SLFN11 is sensitive marker of ATM inhibitor in ESCC.

Breaking the Tumor Chronic Inflammation Balance with a Programmable Release and Multi-Stimulation Engineering Scaffold for Potent Immunotherapy.

Tumor-associated chronic inflammation severely restricts the efficacy of immunotherapy in cold tumors. Here, a programmable release hydrogel-based engineering scaffold with multi-stimulation and reactive oxygen species (ROS)-response (PHOENIX) is demonstrated to break the chronic inflammatory balance in cold tumors to induce potent immunity. PHOENIX can undergo programmable release of resiquimod and anti-OX40 under ROS. Resiquimod is first released, leading to antigen-presenting cell maturation and the transformation of myeloid-derived suppressor cells and M2 macrophages into an antitumor immune phenotype. Subsequently, anti-OX40 is transported into the tumor microenvironment, leading to effector T-cell activation and inhibition of Treg function. PHOENIX consequently breaks the chronic inflammation in the tumor microenvironment and leads to a potent immune response. In mice bearing subcutaneous triple-negative breast cancer and metastasis models, PHOENIX effectively inhibited 80% and 60% of tumor growth, respectively. Moreover, PHOENIX protected 100% of the mice against TNBC tumor rechallenge by electing a robust long-term antigen-specific immune response. An excellent inhibition and prolonged survival in PHOENIX-treated mice with colorectal cancer and melanoma is also observed. This work presents a potent therapeutic scaffold to improve immunotherapy efficiency, representing a generalizable and facile regimen for cold tumors.

Study on the habitat evolution after dam removal in a habitat-alternative tributary of large hydropower station.

The establishment of large hydropower stations in the main stream poses a threat to fish habitats. Selecting suitable tributaries as alternative habitats is a practical measure for ecological environment protection during large hydropower station's construction. The small dams constructed on certain tributaries need to be removed in order to restore river connectivity. The removal of dams will activate hydro-sedimentary dynamics and change the original habitat in terms of topography and hydrodynamics. To explore the evolution of fish habitats following the removal of small dams, a dam-removed reach of a habitat-alternative tributary was selected as the research object, and the model of water-sediment transport and riverbed evolution in strongly disturbed dam-removed reaches and the model of fish habitat suitability evaluation were established. The key parameters calibration and model verification were completed by field monitoring results. The simulation results showed dramatic evolution in the reservoir riverbed in the initial stage after dam removal and during the high discharge period. One year after dam removal, there was a noticeable 4.0 m incision in front of the dam, along with a decrease in channel slope at the dam site from about 4.8% to approximately 1.5%. Downstream of the dam, alterations to the riverbed were mainly concentrated near the dam, and sedimentary bodies with a height of around 2.0 m have formed on the left bank following the high discharge period. The fish habitat in most areas of the dam-removed reach was suitable, except for the downstream high-velocity area. To compare the evolution process of fish habitat under two dam removal periods in wet and dry seasons, two dam removal schemes were implemented in March and June. The results showed that the riverbed evolved more gradually in the March scheme, creating a larger and continuous suitable habitat for fish. Therefore, the March scheme was recommended. By revealing the evolutionary pattern of fish habitat after dam removal, this research provides a reliable model for assessing and restoring habitats in dam-removed reaches, and enjoys significant implications for protecting river ecology in hydropower development reaches.

Mercury contamination is an invisible threat to declining migratory shorebirds along the East Asian-Australasian Flyway.

Exposure to pollutants is a potentially crucial but overlooked driver of population declines in shorebirds along the East Asian-Australasian Flyway. We combined knowledge of moult strategy and life history with a standardised sampling protocol to assess mercury (Hg) contamination in 984 individuals across 33 migratory shorebird species on an intercontinental scale. Over one-third of the samples exceeded toxicity benchmarks. Feather Hg was best explained by moulting region, while habitat preference (coastal obligate vs. non-coastal obligate), the proportion of invertebrates in the diet and foraging stratum (foraging mostly on the surface vs. at depth) also contributed, but were less pronounced. Feather Hg was substantially higher in South China (Mai Po and Leizhou), Australia and the Yellow Sea than in temperate and Arctic breeding ranges. Non-coastal obligate species (Tringa genus) frequently encountered in freshwater habitats were at the highest risk. It is important to continue and expand biomonitoring research to assess how other pollutants might impact shorebirds.

Predicting the Efficacy of Repeated Shockwave Lithotripsy for Treating Patients with Upper Urinary Tract Calculi Using an Artificial Neural Network Model.

PURPOSE: To establish a prediction model for repeated shockwave lithotripsy (SWL) efficacy to help choose an appropriate treatment plan for patients with a single failed lithotripsy, reducing their treatment burden. PATIENTS AND METHODS: The clinical records and imaging data of 304 patients who underwent repeat SWL for upper urinary tract calculi (UUTC) at the Urology Centre of Shiyan People's Hospital between April 2019 and April 2023 were retrospectively collected. This dataset was divided into training (N = 217; 146 males [67.3%] and 71 females [32.7%]) and validation (N = 87; 66 males [75.9%] and 21 females [24.1%]) sets. The overall predictive accuracy of the models was calculated separately for the training and validation.  Receiver operating characteristic (ROC) curves were plotted, and the area under the ROC curve (AUC) was calculated. The normalized importance of each independent variable (derived from the one-way analyses) in the input layer of the artificial neural network (ANN) model for the dependent variable (success or failure in repeat SWL) in the output layer was plotted as a bar chart. RESULTS: This study included 304 patients, of whom 154 (50.7%) underwent successful repeat SWL. Predictive models were constructed in the training set and assessed in the validation set. Fourteen influencing factors were selected as input variables to build an ANN model: age, alcohol, body mass index, sex, hydronephrosis, hematuria, mean stone density (MSD), skin-to-stone distance (SSD), stone heterogeneity index (SHI), stone volume (SV), stone retention time, smoking, stone location, and urinary irritation symptom. The model's AUC was 0.852 (95% confidence interval (CI): 0.8-0.9), and its predictive accuracy for stone clearance in the validation group was 83.3%. The order of importance of the independent variables was MSD > SV > SSD > stone retention time > SHI. CONCLUSION: Establishing an ANN model for repeated SWL of UUTC is crucial for optimizing patient care. This model will be pivotal in providing accurate treatment plans for patients with an initial unsuccessful SWL treatment. Moreover, it can significantly enhance the success rate of subsequent SWL treatments, ultimately alleviating patients' treatment burden.

[Technical Status and Development Trend of Medical Electron Linear Accelerators].

More than 70% of tumor patients require radiotherapy. Medical electron linear accelerators are important high-end radiotherapy equipment for tumor radiotherapy. With the application of artificial intelligence technology in medical electron linear accelerator, radiotherapy has evolved from ordinary radiotherapy to today's intelligent radiotherapy. This study introduces the development history, working principles and system composition of medical electron linear accelerators. It outlines the key technologies for improving the performance of medical linear electron accelerators, including beam control, multi-leaf collimator, guiding technology and dose evaluation. It also looks forward to the development trend of major radiotherapy technologies, such as biological guided radiotherapy, FLASH radiotherapy and intelligent radiotherapy, which provides references for the development of medical electron linear accelerators.

Analysis of the causes of primary revision after unicompartmental knee arthroplasty: A case series.

BACKGROUND: Unicompartmental knee arthroplasty (UKA) has great advantages in the treatment of unicompartmental knee osteoarthritis, but its revision rate is higher than that of total knee arthroplasty. AIM: To summarize and analyse the causes of revision after UKA. METHODS: This is a retrospective case series study in which the reasons for the first revision after UKA are summarized. We analysed the clinical symptoms, medical histories, laboratory test results, imaging examination results and treatment processes of the patients who underwent revision and summarized the reasons for primary revision after UKA. RESULTS: A total of 13 patients, including 3 males and 10 females, underwent revision surgery after UKA. The average age of the included patients was 67.62 years. The prosthesis was used for 3 d to 72 months. The main reasons for revision after UKA were improper suturing of the surgical opening (1 patient), osteophytes (2 patients), intra-articular loose bodies (2 patients), tibial prosthesis loosening (2 patients), rheumatoid arthritis (1 patient), gasket dislocation (3 patients), anterior cruciate ligament injury (1 patient), and medial collateral ligament injury with residual bone cement (1 patient). CONCLUSION: The causes of primary revision after UKA were gasket dislocation, osteophytes, intra-articular loose bodies and tibial prosthesis loosening. Avoidance of these factors may greatly reduce the rate of revision after UKA, improve patient satisfaction and reduce medical burden.

Biomechanical response of decompression alone in lower grade lumbar degenerative spondylolisthesis--A finite element analysis.

BACKGROUND: Previous studies have demonstrated the clinical efficacy of decompression alone in lower-grade spondylolisthesis. A higher rate of surgical revision and a lower rate of back pain relief was also observed. However, there is a lack of relevant biomechanical evidence after decompression alone for lower-grade spondylolisthesis. PURPOSE: Evaluating the biomechanical characteristics of total laminectomy, hemilaminectomy, and facetectomy for lower-grade spondylolisthesis by analyzing the range of motion (ROM), intradiscal pressure (IDP), annulus fibrosus stress (AFS), facet joints contact force (FJCF), and isthmus stress (IS). METHODS: Firstly, we utilized finite element tools to develop a normal lumbar model and subsequently constructed a spondylolisthesis model based on the normal model. We then performed total laminectomy, hemilaminectomy, and one-third facetectomy in the normal model and spondylolisthesis model, respectively. Finally, we analyzed parameters, such as ROM, IDP, AFS, FJCF, and IS, for all the models under the same concentrate force and moment. RESULTS: The intact spondylolisthesis model showed a significant increase in the relative parameters, including ROM, AFS, FJCF, and IS, compared to the intact normal lumbar model. Hemilaminectomy and one-third facetectomy in both spondylolisthesis and normal lumbar models did not result in an obvious change in ROM, IDP, AFS, FJCF, and IS compared to the pre-operative state. Moreover, there was no significant difference in the degree of parameter changes between the spondylolisthesis and normal lumbar models after undergoing the same surgical procedures. However, total laminectomy significantly increased ROM, AFS, and IS and decreased the FJCF in both normal lumbar models and spondylolisthesis models. CONCLUSION: Hemilaminectomy and one-third facetectomy did not have a significant impact on the segment stability of lower-grade spondylolisthesis; however, patients with LDS undergoing hemilaminectomy and one-third facetectomy may experience higher isthmus stress on the surgical side during rotation. In addition, total laminectomy changes the biomechanics in both normal lumbar models and spondylolisthesis models.

Rewiring Photosynthesis by Water-Soluble Fullerene Derivatives for Solar-Powered Electricity Generation.

Natural photosynthesis holds great potential to generate clean electricity from solar energy. In order to utilize this process for power generation, it is necessary to rewire photosynthetic electron transport chains (PETCs) of living photosynthetic organisms to redirect more electron flux toward an extracellular electrode. In this study, a semi-artificial rewiring strategy, which use a water-soluble fullerene derivative to capture electrons from PETCs and donate them for electrical current generation, is proposed. A positively charged fullerene derivative, functionalized with N,N-dimethyl pyrrolidinium iodide, is found to be efficiently taken up by the cyanobacterium Synechocystis sp. PCC 6803. The distribution of this fullerene derivative near the thylakoid membrane, as well as site-specific inhibitor assays and transient absorption spectroscopy, suggest that it can directly interact with the redox centers in the PETCs, particularly the acceptor side of photosystem I (PSI). The internalized fullerene derivatives facilitate the extraction of photosynthetic electrons and significantly enhance the photocurrent density of Synechocystis by approximately tenfold. This work opens up new possibility for the application of fullerenes as an excellent 3D electron carrier in living biophotovoltaics.

Rare-Earth Metal-Organic Framework with Nonplanar Porphyrin Groups for High-Efficiency Photocatalysis.

Nonplanar porphyrins play crucial roles in many biological processes and chemical reactions as catalysts. However, the preparation of artificial nonplanar porphyrins suffers from complicated organic syntheses. Herein, we present a new rare-earth porphyrinic metal-organic framework (RE-PMOF), BUT-233, which is a three-dimensional (3D) framework structure with the flu topology consisting of 4-connected BBCPPP-Ph ligands H4BBCPPP-Ph = 5',5⁗-(10,20-diphenylporphyrin-5,15-diyl)bis([1,1':3',1″-terphenyl]-4,4'' dicarboxylic acid) and 8-connected Eu6 clusters. Noteworthily, the porphyrin cores of the BBCPPP-Ph ligands in BUT-233 are nonplanar with a ruffle-like conformation. In contrast, the porphyrin core in the free ligand H4BBCPPP-Ph is in a nearly ideally planar conformation, as confirmed by its single-crystal structure. BUT-233 is microporous with 6-8 Špores and a Brunauer-Emmett-Teller (BET) surface area of 649 m2/g, as well as high stability in common solvents. The MOF was used as a photocatalyst for the oxidation degradation of a chemical warfare agent model molecule CEES (CEES = 2-chloroethyl ethyl sulfide) under the light-emitting diode (LED) irradiation and an O2 atmosphere at room temperature. CEES was almost completely converted into its nontoxic light-oxidized product CEESO (CEESO = 2-chloroethyl ethyl sulfoxide) in only 5 min with t1/2 = 2 min (t1/2: half-life). Moreover, the toxic deep-oxidized product 2-chloroethyl ethyl sulfone (CEESO2) was not detected. The catalytic activity of BUT-233 was high in comparison with those of some previously reported MOF catalysts. The results of photo/electrochemical property studies suggested that the high catalytic activity of BUT-233 was benefited from the presence of nonplanar porphyrin rings on its pore surface.

Cycasin derivative: a potential embryotoxic component of Atractylodes macrocephala rhizome for limb malformation.

Objective: The rhizome of Atractylodes macrocephala Koidz. (Asteraceae), called Atractylodes macrocephala rhizome (AMR) and known by its traditional name Bai Zhu, is a prominent Chinese herbal medicine employed for preventing miscarriage. However, our previous study revealed that high dosages of AMR administered during pregnancy could cause embryotoxicity but the specific embryotoxic components and their underlying mechanisms remain unclear. This study aimed to screen and identify the potential embryotoxic components of AMR. Methods: The AMR extracts and sub-fractions were analyzed by thin layer chromatography and subsequently screened by in vitro mouse limb bud micromass and mouse whole embryo culture bioassays. The embryotoxic fractions from AMR were further evaluated in vivo using a pregnant mouse model. The structures of the potential embryotoxic components were analyzed using matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF-MS). Results: In vitro and in vivo bioassays revealed that AMR glycoside-enriched sub-fractions (AMR-A-IIa and AMR-A-IIb) exhibited potential embryotoxicity. These sub-fractions, when administered to pregnant animals, increased the incidence of stillbirth and congenital limb malformations. MS spectrometry analysis identified cycasin derivatives in both sub-fractions, suggesting their possible role in the observed limb malformations. However, further experiments are necessary to validate this hypothesis and to elucidate the underlying mechanisms. Conclusions: Our study provides significant scientific evidence on the pharmacotoxicity of AMR, which is important for the safe clinical application of commonly used Chinese herbal medicines during pregnancy.

MolProphet: A One-Stop, General Purpose, and AI-Based Platform for the Early Stages of Drug Discovery.

Artificial intelligence (AI) is an effective tool to accelerate drug discovery and cut costs in discovery processes. Many successful AI applications are reported in the early stages of small molecule drug discovery. However, most of those applications require a deep understanding of software and hardware, and focus on a single field that implies data normalization and transfer between those applications is still a challenge for normal users. It usually limits the application of AI in drug discovery. Here, based on a series of robust models, we formed a one-stop, general purpose, and AI-based drug discovery platform, MolProphet, to provide complete functionalities in the early stages of small molecule drug discovery, including AI-based target pocket prediction, hit discovery and lead optimization, and compound targeting, as well as abundant analyzing tools to check the results. MolProphet is an accessible and user-friendly web-based platform that is fully designed according to the practices in the drug discovery industry. The molecule screened, generated, or optimized by the MolProphet is purchasable and synthesizable at low cost but with good drug-likeness. More than 400 users from industry and academia have used MolProphet in their work. We hope this platform can provide a powerful solution to assist each normal researcher in drug design and related research areas. It is available for everyone at https://www.molprophet.com/.

Design of Far-Infrared High-Efficiency Polarization-Independent Retroreflective Metasurfaces.

Retroreflective gratings serve as fundamental optical elements in nanophotonics, with polarization-independent diffraction efficiency being one of the critical parameters for assessing their performance. In the far-infrared spectral range, traditional retroreflective gratings typically refer to metal echelette gratings, but their diffraction efficiency cannot approach 100% due to metal absorption. In the visible and near-infrared spectral ranges, metal echelette gratings have gradually been replaced by all-dielectric metasurfaces because dielectric materials exhibit negligible absorption at specific wavelengths. However, there is still a lack of relevant research in the far-infrared range, mainly due to the weak control capability of the existing devices over the polarization-independent phase. Here, we propose a kind of all-dielectric retroreflective metasurface composed of asymmetric pillars and freely tunable aperiodic multilayer films. The pillar structure can achieve polarization insensitivity, and the insufficient modulation capability of the dielectric materials can be compensated for by aperiodic Ge/ZnS films. The designed metasurface achieves the diffraction efficiency by RCWA, with the maximum larger than 99% and the overall reaching 95% (9.3-9.6 µm). We have provided detailed explanations of the design methodology and fabrication process. Our work lays the groundwork for further exploration and application of far-infrared lasers.

Metalation of metal-organic frameworks: fundamentals and applications.

Metalation of metal-organic frameworks (MOFs) has been developed as a prominent strategy for materials functionalization for pore chemistry modulation and property optimization. By introducing exotic metal ions/complexes/nanoparticles onto/into the parent framework, many metallized MOFs have exhibited significantly improved performance in a wide range of applications. In this review, we focus on the research progress in the metalation of metal-organic frameworks during the last five years, spanning the design principles, synthetic strategies, and potential applications. Based on the crystal engineering principles, a minor change in the MOF composition through metalation would lead to leveraged variation of properties. This review starts from the general strategies established for the incorporation of metal species within MOFs, followed by the design principles to graft the desired functionality while maintaining the porosity of frameworks. Facile metalation has contributed a great number of bespoke materials with excellent performance, and we summarize their applications in gas adsorption and separation, heterogeneous catalysis, detection and sensing, and energy storage and conversion. The underlying mechanisms are also investigated by state-of-the-art techniques and analyzed for gaining insight into the structure-property relationships, which would in turn facilitate the further development of design principles. Finally, the current challenges and opportunities in MOF metalation have been discussed, and the promising future directions for customizing the next-generation advanced materials have been outlined as well.

Phosphoric Acid Catalyzed N-Addition/ C-Addition Reaction of 3-Vinyl Indoles with Pyrazole/Pyrazolone to Construct Pyrazole-Substituted 3-(1-Heteroarylethyl)-indole Scaffolds.

Developing a highly efficient atom-economic method for the preparation of 3-(1-heteroarylethyl)-indole scaffolds is of significant value in pharmaceutical and agricultural chemistry. Herein, a phosphoric acid-catalyzed N-addition reaction of 3-vinyl indoles with pyrazoles and C-addition reaction of 3-vinyl indoles with pyrazolones were developed. A series of pyrazole-substituted 3-(1-heteroarylethyl)-indole scaffolds were synthesized in excellent yields (up to 99% yield) under mild reaction conditions. A reasonable reaction mechanism was proposed to explain the experimental results.