Overall thermal sensation and comfort prediction with different model combinations: Cold and hot step-change environments in winter.

Currently, numerous thermal comfort models have been proposed; however, research on the combination of different models is lacking. This study aims to predict the overall thermal sensation (OTS*) and thermal comfort (OTC*) with different model combinations under hot and cold step changes. Three cold- and hot-shock processes are designed in the climate chamber. Accordingly, the skin temperature, thermal sensation, and thermal comfort votes of 16 participants are collected. The impacts of winter hot and cold step changes on subjective votes and skin temperatures are evaluated. Further, the OTS* and OTC* values are calculated, and their accuracy under different model combinations is analyzed. The results reveal that thermal sensation changes in human body exhibit distinct asymmetry under the cold and hot step-changes, except for the cycle of "15-30-15 °C" (I15). The parts farther from the core area become more asymmetrical after the step changes. The single models exhibit the highest accuracy in different model combinations. The combined form of a single model is recommended for thermal sensation or comfort prediction.

A thermodynamic study of capillary electrochromatographic retention of aromatic hydrocarbons on a lauryl acrylate porous polymer monolithic column with measured phase ratio.

The phase ratio of a chromatographic system is an important measurement that has long been estimated or calculated, but rarely directly measured. This study utilized a nanoflow liquid chromatography instrument to more accurately measure the phase ratio for a lauryl acrylate porous polymer monolith. Direct measurement of the phase ratio, and its dependence on temperature, allows for a better understanding of the thermodynamics of retention of small analytes. This study investigates the retention of an alkyl benzene series, toluene to octylbenzene, via capillary electrochromatography. The phase ratio was determined to be 0.202 at 303 K and 0.213 at 333 K. Using the directly measured phase ratio, entropic contributions to retention can also be obtained. Therefore, the Gibbs free energy calculations from these measurements and methods can give insight to modes of retention. The free energy of retention for toluene is -3.97 kJ/mol at 303 K and -3.78 kJ/mol at 333 K. The trends for enthalpy, entropy, and Gibbs free energy of transfer show that retention is enthalpically driven in this capillary electrochromatography (CEC) porous polymer monolith system.

Expand-and-Randomize: An Algebraic Approach to Secure Computation.

We consider the secure computation problem in a minimal model, where Alice and Bob each holds an input and wish to securely compute a function of their inputs at Carol without revealing any additional information about the inputs. For this minimal secure computation problem, we propose a novel coding scheme built from two steps. First, the function to be computed is expanded such that it can be recovered while additional information might be leaked. Second, a randomization step is applied to the expanded function such that the leaked information is protected. We implement this expand-and-randomize coding scheme with two algebraic structures-the finite field and the modulo ring of integers, where the expansion step is realized with the addition operation and the randomization step is realized with the multiplication operation over the respective algebraic structures.

Total Synthesis of (+)-Granatumine A and Related Bislactone Limonoid Alkaloids via a Pyran to Pyridine Interconversion.

We report the first total synthesis of (+)-granatumine A, a limonoid alkaloid with PTP1B inhibitory activity, in ten steps. Over the course of this study, two key methodological advances were made: a cost-effective procedure for ketone α,ß-dehydrogenation using allyl-Pd catalysis, and a Pd-catalyzed protocol to convert epoxyketones to 1,3-diketones. The central tetrasubstituted pyridine is formed by a convergent Knoevenagel condensation and carbonyl-selective electrocyclization cascade, which was followed by a direct transformation of a 2 H-pyran to a pyridine. These studies have led to the structural revision of two members of this family.

A Strategy toward New Low-Dimensional Hybrid Halide Perovskites with Anionic Spacers.

The low-dimensional halide perovskites have received enormous attention due to their unique photovoltaic and optoelectronic performances. Periodic spacers are used to inhibit the growth of 3D perovskite and fabricate a 2D counterpart with layered structure, mostly based on organic/inorganic cations. Herein, by introducing organic anions (e.g., pentanedioic acid (PDA) and hexanedioic acid (HDA) simultaneously), leaf-shaped (Cs3 Pb2 Br5 )2 (PDA-HDA) microplates with low-dimensional structure are synthesized. They also exhibit significant photoluminescence (PL) centered at 540 nm with a narrow emission peak. The synthesis of single crystals of Pb(PDA) and Pb(HDA) allows to further clarify the crystal structure of (Cs3 Pb2 Br5 )2 (PDA-HDA) perovskite and its structural evolution mechanism. Moreover, the cooperative introduction of dicarboxylic acid pairs with appropriate lengths is thermodynamically favored for the low-dimensional perovskite crystallization. The temperature-dependent PL indicates a V-shaped Stokes shift with elevated temperature that could be associated with the localization of excitons in the inorganic layers between organic dicarboxylic acid molecules. This work demonstrates low-dimensional halide perovskite with anionic spacers, which also opens up a new approach to the growth of low-dimensional organic-inorganic hybrid perovskite crystals.

Stabilizing RbPbBr3 Perovskite Nanocrystals through Cs+ Substitution.

ABX3 -type halide perovskite nanocrystals (NCs) have been a hot topic recently due to their fascinating optoelectronic properties. It has been demonstrated that A-site ions have an impact on their photophysical and chemical properties, such as the optical band gap and chemical stability. The pursuit of halide perovskite materials with diverse A-site species would deepen the understanding of the structure-property relationship of the perovskite family. In this work we have attempted to synthesize rubidium-based perovskite NCs. We have discovered that the partial substitution of Rb+ by Cs+ help to stabilize the orthorhombic RbPbBr3 NCs at low temperature, which otherwise can only be obtained at high temperature. The inclusion of Cs+ into the RbPbBr3 lattice results in highly photoluminescent Rb1-x Csx PbBr3 NCs. With increasing amounts of Cs+ , the band gaps of the Rb1-x Csx PbBr3 NCs decrease, leading to a redshift of the photoluminescence peak. Also, the Rb1-x Csx PbBr3 NCs (x=0.4) show good stability under ambient conditions. This work demonstrates the high structural flexibility and tunability of halide perovskite materials through an A-site cation substitution strategy and sheds light on the optimization of perovskite materials for application in high-performance optoelectronic devices.

Analysis of chain length, substitution patterns, and unsaturation of AM-404 derivatives as 20S proteasome stimulators.

Proteasome-mediated degradation of proteins is a vital cellular process and is performed by the ubiquitin-dependent proteasome system (UPS) and the ubiquitin-independent proteasome system (UIPS). While both systems are necessary to maintain healthy cell function, many disease states are characterized by reduced activity of the UPS, and the UIPS cannot by itself maintain proper protein levels. It has been suggested that the 20S core particle (20S CP), the isoform of the proteasome in the UIPS that can degrade proteins without a ubiquitin tag, can be stimulated with a small molecule to assist the 20S CP to accept and hydrolyze substrates more rapidly. Several small molecule stimulators of the 20S CP have since been discovered, including AM-404, an arachidonic acid derivative. AM-404 has previously been shown to inhibit fatty acid amide hydrolase activity. We wished to evaluate what structural components of AM-404 are required to stimulate the 20S CP with the long-term goal of using this information to design a stimulator with better drug-like qualities. We synthesized numerous derivatives of AM-404, varying the chain length, substitutions, and degree of unsaturation. Through this endeavor, we obtained several molecules capable of stimulating the 20S CP to various degrees. We discovered that though chain length is important, the presence of a cis-alkene in a specific location in the aliphatic chain has the greatest impact on the ability to stimulate the 20S CP. Two of the derivatives maintain modest stimulatory activity, and have improved toxicity over AM-404.

Chemokine and Cytokine Cascade Caused by Skewing of the Th1-Th2 Balance Is Associated with High Intracranial Pressure in HIV-Associated Cryptococcal Meningitis.

PURPOSE: Serum cytokines/chemokines play important roles in cryptococcal meningitis, but it is unclear whether cytokines/chemokines in cerebrospinal fluid (CSF) contribute to high intracranial pressure (HICP) in HIV-associated cryptococcal meningitis (HCM). METHODS: CSF cytokines/chemokines were assayed in 17 HIV-uninfected patients, 26 HIV-infected patients without CNS infection, and 39 HCM patients at admission. Principal component analysis and correlation and logistic regression analyses were used to assess the relationships between these parameters. RESULTS: The CSF Th1, Th2, and macrophage cytokines showed an obvious increase in HCM patients as compared to the HIV-uninfected patients and HIV-infected patients without CNS infection. CSF IL-6, GM-CSF, and IL-8 were positively correlated with CSF fungal burden. Serum CD4 count, CSF Th1 cytokines (TNF-α, TNF-ß, IL-12, IL-1ß, IL-12, IL-1α, TNF-α, TNF-ß, IL-12, IL-1γ, and IL-12) and Th2 cytokines (IL-4 and IL-10) contribute to HICP. CONCLUSION: Overall, the present findings indicated that both pro- and anti-inflammatory cytokines of Th1, Th2, and macrophage origin contributed to the development of HCM. Specifically, the chemokine and cytokine cascade caused by skewing of the Th1-Th2 balance and reduced CD4 count were found to be important contributors to HICP. Summary. Our research suggested that chemokine and cytokine cascade caused by skewing of the Th1-Th2 balance in HIV-infected patients played more important role than Cryptococcus numbers and size in CSF on the development of high intracranial pressure in HIV-associated cryptococcal meningitis, providing a new understanding of mechanisms of HCM.

Qiliqiangxin Attenuates Cardiac Remodeling via Inhibition of TGF-ß1/Smad3 and NF-κB Signaling Pathways in a Rat Model of Myocardial Infarction.

BACKGROUND/AIMS: Qiliqiangxin (QL), a traditional Chinese medicine, has been demonstrated to be effective and safe for the treatment of chronic heart failure. Left ventricular (LV) remodeling causes depressed cardiac performance and is an independent determinant of morbidity and mortality after myocardial infarction (MI). Our previous studies have shown that QL exhibits cardiac protective effects against heart failure after MI. The objective of this study was to explore the effects of QL on myocardial fibrosis in rats with MI and to investigate the underlying mechanism of these effects. METHODS: A rat model of acute myocardial infarction was induced by ligating the left anterior descending coronary artery. The rats were treated with QL (1.0 g/kg/day) for 4 weeks after surgery. Echocardiography and histology examination were performed to evaluate heart function and fibrosis, respectively. Protein levels of transforming growth factor-ß1 (TGF-ß1), phosphorylated Smad3 (p-Smad3), phosphorylated Smad7 (p-Smad7), collagen I (Col- I), alpha smooth muscle actin (a-SMA), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), nuclear factor κB (NF-κB), and phosphorylated inhibitor of kappa B alpha (p-IκBα) were measured by western blot analysis. RESULTS: QL treatment ameliorated adverse cardiac remodeling 8 weeks after AMI, including better preservation of cardiac function, decreased inflammation, and reduced fibrosis. In addition, QL treatment reduced Col-I, a-SMA, TGF-ß1, and p-Smad3 expression levels but increased p-Smad7 levels in postmyocardial infarct rat hearts. QL administration also reduced the elevated levels of cardiac inflammation mediators, such as TNF-α and IL-6, as well as NF-κB and p-IκBα expression. CONCLUSIONS: QL therapy exerted protective effects against cardiac remodeling potentially by inhibiting TGF-ß1/Smad3 and NF-κB signaling pathways, thereby preserving cardiac function, as well as reducing myocardial inflammation and fibrosis.

[Huotan Jiedu Tongluo decoction alleviates early atherosclerosis of rabbits by inhibiting eNOS uncoupling pathway].

The aim of this paper was to study the curative effect of Huotan Jiedu Tongluo (HTJDTL) decoction on a rabbit model with early atherosclerosis (AS),and furtherly to explore whether it could inhibit the BH4/eNOS uncoupling ROS or not. Twenty-four Japanese white rabbits were randomly divided into sham operation group, model group, HTJDTL decoction group and atorvastatin group. Rabbit models with early atherosclerosis were established by high fat diet, nitrogen drying and carotid artery balloon injury. The rabbits were sacrificed at 7th days after balloon injury and several parameters were measured. The pathological morphology of the common carotid artery was observed by HE staining. The blood lipids were detected by peroxidase method. The ratio of vascular eNOS dimer and monomer was measured by Western blot. The ELISA and biochemical technology were respectively used for testing BH4 and ROS levels in serum. The results showed that compared with the sham operation group, the model group had mild stenosis of the common carotid artery lumen, uneven intimal hyperplasia, lipid deposition in the intima and media, and obvious hyperplasia of the adventitia with inflammatory cell infiltration. The HTJDTL decoction could significantly inhibit the intimal hyperplasia compared with the model group, meanwhile, reduce the lipid deposition of the media and the infiltration of the adventitial cells. Compared with the sham operation group, the blood lipids and ROS of the model animals significantly increased, but BH4 and the ratio of eNOS dimer/monomer decreased. Compared with the model group, HTJDTL decoction significantly reduced the TC, ox-LDL and ROS levels, and also up-regulated eNOS dimer/monomer ratio, but it increased BH4 trend without statistical difference. According to the results, it was found that HTJDTL decoction couldsignificantly prevent and improve the vascular remodeling of rabbits model with early atherosclerosis. The mechanism of decoction may largely be related to the inhibition of BH4/eNOS uncoupling and the reduction of oxidative stress.

Allyl-Palladium-Catalyzed α,ß-Dehydrogenation of Carboxylic Acids via Enediolates.

A highly practical and step-economic α,ß-dehydrogenation of carboxylic acids via enediolates is reported through the use of allyl-palladium catalysis. Dianions underwent smooth dehydrogenation when generated using Zn(TMP)2 ⋅2 LiCl as a base in the presence of excess ZnCl2 , thus avoiding the typical decarboxylation pathway of these substrates. Direct access to 2-enoic acids allows derivatization by numerous approaches.

Allyl-Palladium-Catalyzed Ketone Dehydrogenation Enables Telescoping with Enone α,ß-Vicinal Difunctionalization.

The telescoping of allyl-palladium catalyzed ketone dehydrogenation with organocuprate conjugate addition chemistry allows for the introduction of aryl, heteroaryl, vinyl, acyl, methyl, and other functionalized alkyl groups chemoselectively to a wide variety of unactivated ketone compounds via their enone counterparts. The compatibility of the dehydrogenation conditions additionally allows for efficient trapping of the intermediate enolate with various electrophiles. The utility of this approach is demonstrated by comparison to several previously reported multistep sequences.

[Effects of Qili Qiangxin Capsule on Lung Structural Remodeling in Heart Failure Rats after Myocardial Infarction and Its Mechanism].

Objective To observe the effect of Qili Qiangxin Capsule (QQC) in improving lung struc- tural remodeling on heart failure (HF) rats after myocardial infarction (Ml) and to study its possible mecha- nism. Methods The proximal left anterior descending branch of coronary artery was ligated using a terylene suture to establish acute myocardial infarction (AMI) rat model. After successful AMI modeling rats were ran- domly divided into the model group (intragastrically administered with distilled water at 1 mL/100 g, n =13) and the QQC group (intragastrically administered with QQC at the daily dose of 1 g/kg, n =9). And the sham-opera- tion group (intragastrically administered with distilled water at 1 mL/100 g, n =10) was also set up. After four weeks intervention heart functions of rats were detected using echocardiography. The pathological changes of lung structures were observed by HE and Masson staining method. Protein expressions of lung α-SMA, Collagen I, TGF-ß1, and p-Smad3 of the lung tissue were detected by immunohistochemistry and Western blot. Re- sults Compared with the sham-operation group, ejection fraction (EF) and fraction shortening (FS) decreased (P <0. 05) , protein expressions of lung left ventricular internal diastolic diameter (LVIDd), left ventric- ular internal systolic diameter (LVIDs), end diastolic volume (EDV), end systolic volume (ESV), α-smooth muscle actin (a-SMA), Collagen I, tumor growth factor-ß1 (TGF-ß1), and p-Smad3 increased (P <0.05) in the model group. The muscularized small arteries ratio and collagen area of the lung tissue increased in the model group (P <0. 05). Compared with the model group, EF and FS increased (P <0. 05), protein expressions of LVIDs, ESV, α-SMA, Collagen I, TGF-ß, , and p-Smad3 decreased (P <0.05) in the QQC group. The muscular- ized small arteries ratio and collagen area of the lung tissue decreased in the QQC group (P <0. 05). Conclusion QQC could improve lung structural remodeling degree of HF rats after MI, and its possible mechanism might be achieved by regulating TGF-beta,/Smad3 signaling pathways.

Diastereoselective formation of aziridines from diazocarbonyl compounds and N-(O-pivaloylated D-galactosyl)benzylideneamines and ring-opening reactions with p-toluenethiol.

N-Galactosyl aziridines were synthesized via BF3·OEt2 promoted addition of carbenes generated from diazocarbonyl compounds with O-pivaloylated ß-D-galactosylimines in good yields and high diastereoselectivity. The ring-opening reactions with p-toluenethiol of the aziridines provided enantiometrically pure ß-S-substituted phenylalanine derivatives in a highly regioselective manner.

Training-free CryoET Tomogram Segmentation.

Cryogenic Electron Tomography (CryoET) is a useful imaging technology in structural biology that is hindered by its need for manual annotations, especially in particle picking. Recent works have endeavored to remedy this issue with few-shot learning or contrastive learning techniques. However, supervised training is still inevitable for them. We instead choose to leverage the power of existing 2D foundation models and present a novel, training-free framework, CryoSAM. In addition to prompt-based single-particle instance segmentation, our approach can automatically search for similar features, facilitating full tomogram semantic segmentation with only one prompt. CryoSAM is composed of two major parts: 1) a prompt-based 3D segmentation system that uses prompts to complete single-particle instance segmentation recursively with Cross-Plane Self-Prompting, and 2) a Hierarchical Feature Matching mechanism that efficiently matches relevant features with extracted tomogram features. They collaborate to enable the segmentation of all particles of one category with just one particle-specific prompt. Our experiments show that CryoSAM outperforms existing works by a significant margin and requires even fewer annotations in particle picking. Further visualizations demonstrate its ability when dealing with full tomogram segmentation for various subcellular structures. Our code is available at: https://github.com/xulabs/aitom.

g-C3N4 as ballistic electron transport "Tunnel" in CsPbBr3-based ternary photocatalyst for gas phase CO2 reduction.

Perovskite CsPbBr3 quantum dot shows great potential in artificial photosynthesis, attributed to its outstanding optoelectronic properties. Nevertheless, its photocatalytic activity is hindered by insufficient catalytic active sites and severe charge recombination. In this work, a CsPbBr3@Ag-C3N4 ternary heterojunction photocatalyst is designed and synthesized for high-efficiency CO2 reduction. The CsPbBr3 quantum dots and Ag nanoparticles are chemically anchored on the surface of g-C3N4 sheets, forming an electron transfer tunnel from CsPbBr3 quantum dots to Ag nanoparticles via g-C3N4 sheets. The resulting CsPbBr3@Ag-C3N4 ternary photocatalyst, with spatial separation of photogenerated carriers, achieves a remarkable conversion rate of 19.49 µmol·g-1·h-1 with almost 100 % CO selectivity, a 3.13-fold enhancement in photocatalytic activity as compared to CsPbBr3 quantum dots. Density functional theory calculations reveal the rapid CO2 adsorption/activation and the decreased free energy (0.66 eV) of *COOH formation at the interface of Ag nanoparticles and g-C3N4 in contrast to the g-C3N4, leading to the excellent photocatalytic activity, while the thermodynamically favored CO desorption contributes to the high CO selectivity. This work presents an innovative strategy of constructing perovskite-based photocatalyst by modulating catalyst structure and offers profound insights for efficient CO2 conversion.

Transcriptomic analysis reveals the critical role of chemokine signaling in the anti-atherosclerosis effect of Xuefu Zhuyu decoction.

ETHNOPHARMACOLOGICAL RELEVANCE: The process of atherosclerosis (AS) is complicated. Transcriptomics technology can assist in discovering the underlying mechanisms and exploring the key targets of Traditional Chinese Medicine (TCM) against atherosclerosis. AIM: This study aimed to investigate targets and signaling pathways significantly related to AS and the potential intervention targets of Xuefu Zhuyu decoction by transcriptomics. MATERIALS AND METHODS: AS models were established by subjecting ApoE-/-mice to an 8-week high-fat diet. Structural changes and plaque formation in the aortic root were observed using hematoxylin-eosin staining (HE staining), while Oil Red O staining was employed to visualize lipid deposition within the aortic root plaque. Movat staining and immunohistochemical staining were conducted to examine the components present in the aortic root plaque. Macrophage content within the plaque was observed through immunofluorescence. Additionally, mRNA sequencing was performed on aortic tissues to identify differentially expressed genes. Enrichment analysis was performed using GO and KEGG analysis. Visualization of the protein-protein interaction (PPI) network was achieved using Cytoscape 3.7.1 and STRING. Western blotting (WB) was employed to assess the protein expression of major differentially expressed genes in the aortic tissue. The drug freeze-dried powder of Xuefu Zhuyu decoction was prepared and the RAW264.7 cells were induced by lipopolysaccharide (LPS) to build an in vitro model. Real-time quantitative PCR was employed to measure the mRNA expression of major differential genes. RESULTS: After ApoE-/- mice were fed with an 8-week high-fat diet, observable changes included the thinning of the aortic root wall, the accumulation of foam cells within the plaque, and the formation of cholesterol crystals in the model group. Treatment with Xuefu Zhuyu (XFZY) decoction for 12 weeks significantly reduced the lipid deposition and the number of macrophages (P < 0.05) and significantly increased the collagen content within the plaque (P < 0.01). Enrichment analysis revealed a high enrichment of the Cytokine-cytokine receptor interaction pathway and Chemokine signaling pathway. Noteworthy genes involved in this response included Ccl12, Ccl22, Cx3cr1, Ccr7, Ccr2, Tnfrsf25, and Gdf5. Xuefu Zhuyu decoction significantly downregulated the expression of CX3CL1 and CX3CR1 (P < 0.05) and upregulated the expression of GDF5 (P < 0.01). Compared with control group, in cell models, the mRNA expressions of Ccl12, Ccl22, and Ccr2 were significantly upregulated (P < 0.05 or P < 0.01). Xuefu Zhuyu decoction significantly downregulated the expression of Ccl12, Ccl22, Cx3cr1, Ccr7 and Ccr2 (P < 0.05 or P < 0.01). CONCLUSION: Xuefu Zhuyu decoction demonstrates effective regulation of plaque components, retarding plaque progression and preserving plaque stability by modulating lipid metabolism and inflammatory responses. Subsequent transcriptome analysis identified the Cytokine-cytokine receptor interaction and Chemokine signaling pathway as potential key pathways for the therapeutic effects of Xuefu Zhuyu decoction. This insight not only provides crucial avenues for further exploration into the mechanisms underlying Xuefu Zhuyu decoction but also offers valuable perspectives and hypotheses for enhancing disease prevention and treatment strategies.

TWIST1+FAP+ fibroblasts in the pathogenesis of intestinal fibrosis in Crohn's disease.

Intestinal fibrosis, a severe complication of Crohn's disease (CD), is characterized by excessive extracellular matrix (ECM) deposition and induces intestinal strictures, but there are no effective anti-fibrosis drugs available for clinical application. We performed single-cell RNA sequencing (scRNA-seq) of fibrotic and non-fibrotic ileal tissues from CD patients with intestinal obstruction. Analysis revealed mesenchymal stromal cells (MSCs) as the major producers of ECM and the increased infiltration of its subset FAP+ fibroblasts in fibrotic sites, which was confirmed by immunofluorescence and flow cytometry. Single cell transcriptomic profiling of chronic Dextran Sulfate Sodium Salt (DSS) murine colitis model revealed Cd81+Pi16- fibroblasts exhibited transcriptomic and functional similarities to human FAP+ fibroblasts. Consistently, FAP+ fibroblasts were identified as the key subtype with the highest level of ECM production in fibrotic intestines. Furthermore, specific knockout or pharmacological inhibition of TWIST1, which was highly expressed by FAP+ fibroblasts, could significantly ameliorate fibrosis in mice. In addition, TWIST1 expression was induced by CXCL9+ macrophages enriched in fibrotic tissues via IL-1ß and TGF-ß signal. These findings suggest the inhibition of TWIST1 as a promising strategy for CD fibrosis treatment.

Autoimmune pancreatitis: A bibliometric analysis from 2002 to 2022.

Background/Objectives: Autoimmune pancreatitis (AIP) is a distinct form of pancreatic inflammatory disease that responds well to glucocorticoid therapy. Knowledge on AIP has rapidly evolved over the past two decades. Based on bibliometric analysis, this study aimed to assess the research status of AIP over the past two decades and determine the research focus and emerging topics. Methods: AIP-related publications published between January 1, 2002, and June 6, 2022, were retrieved from the Web of Science Core Collection. Bibliometric data were analyzed using HisCite, VOSviewer, CiteSpace, and bibliometrix package. Annual output, leading countries/regions, active institutions and authors, core journals and references, and keywords of AIP were evaluated. Results: Overall, 1,772 publications were retrieved from 501 journals by 6,767 authors from 63 countries/regions. Japan published articles on AIP the most (n=728, 41.1%), followed by the United States (n=336, 19%), Germany (n=147, 8.3%), China (n=127, 7%), and Italy (n=107, 6%). The top three most prolific authors were Terumi Kamisawa from Tokyo Metropolitan Komagome Hospital (n=117), Kazuichi Okazaki from Kansai Medical University (n=103), and Shigeyuki Kawa from Matsumoto Dental University (n=94). Pancreas was the most productive journal regarding AIP research (n=95), followed by the Journal of Gastroenterology (n=67), Internal Medicine (n=66), Pancreatology (n=63), and World Journal of Gastroenterology (n=62). "Diagnosis" was the most mentioned keyword. "Risk," "malignancy," "outcome," "22-gauge needle," and "fine-needle aspiration" were recognized as emerging topics. Conclusion: Japan was the leading country in AIP research. Research papers were mainly published in specialized journals. Diagnosis was the research focus. Long-term outcomes and pancreatic tissue acquisition were recognized as research frontiers for AIP.

Targeted protein degrader development for cancer: advances, challenges, and opportunities.

Anticancer-targeted therapies inhibit various kinases implicated in cancer and have been used in clinical settings for decades. However, many cancer-related targets are proteins without catalytic activity and are difficult to target using traditional occupancy-driven inhibitors. Targeted protein degradation (TPD) is an emerging therapeutic modality that has expanded the druggable proteome for cancer treatment. With the entry of new-generation immunomodulatory drugs (IMiDs), selective estrogen receptor degraders (SERDs), and proteolysis-targeting chimera (PROTAC) drugs into clinical trials, the field of TPD has seen explosive growth in the past 10 years. Several challenges remain that need to be tackled to increase successful clinical translation of TPD drugs. We present an overview of the global landscape of clinical trials of TPD drugs over the past decade and summarize the clinical profiles of new-generation TPD drugs. In addition, we highlight the challenges and opportunities for the development of effective TPD drugs for future successful clinical translation.