Design of FK866-Based Degraders for Blocking the Nonenzymatic Functions of Nicotinamide Phosphoribosyltransferase.

Nicotinamide phosphoribosyltransferase (NAMPT) is an attractive therapeutic target for treating select cancers. There are two forms of NAMPT: intracellular NAMPT (iNAMPT, the rate-limiting enzyme in the mammalian NAD+ main synthetic pathway) and extracellular NAMPT (eNAMPT, a cytokine with protumorigenic function). Reported NAMPT inhibitors only inhibit iNAMPT and show potent activities in preclinical studies. Unfortunately, they failed to show efficacy due to futility and toxicity. We developed a series of FK866-based NAMPT-targeting PROTACs and identified LYP-8 as a potent and effective NAMPT degrader that simultaneously diminished iNAMPT and eNAMPT. Importantly, LYP-8 demonstrated superior efficacy and safety in mice when compared to the clinical candidate, FK866. This study highlights the importance and feasibility of applying PROTACs as a superior strategy for interfering with both the enzymatic function of NAMPT (iNAMPT) and nonenzymatic function of NAMPT (eNAMPT), which is difficult to achieve with conventional NAMPT inhibitors.

Three-Dimensional ERT Advanced Detection Method with Source-Position Electrode Excitation for Tunnel-Boring Machines.

Tunnel-boring machines (TBMs) are widely used in urban underground tunnel construction due to their fast and efficient features. However, shield-tunnel construction faces increasingly complex geological environments and may encounter geological hazards such as faults, fracture zones, water surges, and collapses, which can cause significant property damage and casualties. Existing geophysical methods are subject to many limitations in the shield-tunnel environment, where the detection space is extremely small, and a variety of advanced detection methods are unable to meet the required detection requirements. Therefore, it is crucial to accurately detect the geological conditions in front of the tunnel face in real time during the tunnel boring process of TBM tunnels. In this paper, a 3D-ERT advanced detection method using source-position electrode excitation is proposed. First, a source-position electrode array integrated into the TBM cutterhead is designed for the shield-tunnel construction environment, which provides data security for the inverse imaging of the anomalous bodies. Secondly, a 3D finite element tunnel model containing high- and low-resistance anomalous bodies is established, and the GREIT reconstruction algorithm is utilized to reconstruct 3D images of the anomalous body in front of the tunnel face. Finally, a physical simulation experiment platform is built, and the effectiveness of the method is verified by laboratory physical modeling experiments with two different anomalous bodies. The results show that the position and shape of the anomalous body in front of the tunnel face can be well reconstructed, and the method provides a new idea for the continuous detection of shield construction tunnels with boring.

Combination of Simo Decoction and Golden Bifid alleviates functional dyspepsia through a mechanism involving intestinal microbiota and short-chain fatty acids.

BACKGROUND AND STUDY AIMS: The integration of traditional Chinese medicine and Western medicine holds promise for the treatment of gastrointestinal disorders, which are influenced by intestinal microbiota and metabolites. This study reports a possible mechanism for the combination of Simo Decoction and Golden Bifid in functional dyspepsia (FD) by regulating intestinal microbiota and short-chain fatty acids (SCFAs). PATIENTS AND METHODS: A mouse model of food stagnation was constructed and treated with Simo Decoction combined with different concentrations of Golden Bifid. Meta-genomics sequencing was conducted to analyze the cecum contents of the mice. Following analyses of the composition and abundance of intestinal microbiota, gas chromatography-mass spectrometry was performed to measure SCFAs in the colonic content of mice. Finally, ELISA was utilized to determine the levels of pro-inflammatory factors in the duodenal mucosa of mice and the infiltration of eosinophils in the duodenum was observed by immunohistochemical staining. RESULTS: Combination of Simo Decoction and Golden Bifid more significantly alleviated dyspepsia in mice with food stagnation compared with Simo Decoction alone. The optimal ratio of combined treatment was 0.0075 mL/g (body weight) Simo Decoction and 0.0032 mg/g (body weight) Golden Bifid. The combined treatment increased the abundance of Bifidobacterium and Bacteroides in the intestine. The levels of SCFAs in the colonic contents of mice were increased after the combined treatment, contributing to diminished pro-inflammatory factors in the duodenal mucosa and reduced eosinophil infiltration. CONCLUSION: Combination of Simo Decoction and Golden Bifid increases the abundance of Bacteroides and Bifidobacterium and promotes the production of SCFAs, which is instrumental for alleviation of FD.

Elemental diet preventative effects for adverse events during chemotherapy in patients with esophageal cancer - A systematic review and meta-analysis.

The effectiveness of an elemental diet (ED) for preventing adverse events (AEs) during chemotherapy for patients with esophageal cancer (EC) remains unclear. The aim of this meta-analysis was to comprehensively assess the efficacy of ED for preventing AE in EC patients during chemotherapy. Medline (via PubMed), Embase, the Cochrane Library, and Web of Science were searched to retrieve prospective and randomized studies published before April 12, 2023. The odds ratio (OR) of each AE was calculated using Review Manger 5.4.1. The risk of bias was assessed, and a random effect model-based meta-analysis was used to analyze the available data. Four prospective and randomized studies involving 237 patients were identified after a systematic search. Regarding gastrointestinal toxicities, the findings indicated a trend toward a decrease in the risk of mucositis (OM) (OR = 0.54, 95 % CI: 0.25-1.14), constipation (OR = 0.87, 95 % CI: 0.49-1.53), and anorexia (OR = 0.99, 95 % CI: 0.32-3.05), as well as an increasing trend in the risk of diarrhea (OR = 1.48, 95 % CI: 0.79-2.79), among patients treated with ED. However, none of these reached statistical significance. For hematological toxicities, the risk of all-grade neutropenia (OR = 0.28, 95 % CI: 0.14-0.57), grade ≥ 2 leucopenia (OR = 0.43, 95 % CI: 0.22-0.84), grade ≥ 2 neutropenia (OR = 0.34, 95 % CI: 0.17-0.67), and grade ≥ 3 neutropenia (OR = 0.28, 95 % CI: 0.12-0.63) was significantly decreased. There is no firm evidence confirming the preventive effect of an ED against OM or diarrhea. However, an ED may potentially be helpful in preventing neutropenia and leucopenia.

High synthetic cost-amino acids reduce member interactions of acetate-degrading methanogenic microbial community.

Introduction: The cooperation among members of microbial communities based on the exchange of public goods such as 20 protein amino acids (AAs) has attracted widespread attention. However, little is known about how AAs availability affects interactions among members of complex microbial communities and the structure and function of a community. Methods: To investigate this question, trace amounts of AAs combinations with different synthetic costs (low-cost, medium-cost, high-cost, and all 20 AAs) were supplemented separately to acetate-degrading thermophilic methanogenic reactors, and the differences in microbial community structure and co-occurring networks of main members were compared to a control reactor without AA supplementation. Results: The structure of the microbial community and the interaction of community members were influenced by AAs supplementation and the AAs with different synthetic costs had different impacts. The number of nodes, links, positive links, and the average degree of nodes in the co-occurrence network of the microbial communities with AAs supplementation was significantly lower than that of the control without AAs supplementation, especially for all 20 AAs supplementation followed by the medium- and high-cost AAs supplementation. The average proportion of positive interactions of microbial members in the systems supplemented with low-cost, medium-cost, high-cost, all AAs, and the control group were 0.42, 0.38, 0.15, 0.4, and 0.45, respectively. In addition, the ecological functions of community members possibly changed with the supplementation of different cost AAs. Discussion: These findings highlight the effects of AAs availability on the interactions among members of complex microbial communities, as well as on community function.

Gut bacteria exacerbates TNBS-induced colitis and kidney injury through oxidative stress.

Gut microbiota has been implicated in the initiation and progression of various diseases; however, the underlying mechanisms remain elusive and effective therapeutic strategies are scarce. In this study, we investigated the role and mechanisms of gut microbiota in TNBS-induced colitis and its associated kidney injury while evaluating the potential of dietary protein as a therapeutic intervention. The intrarectal administration of TNBS induced colitis in mice, concurrently with kidney damage. Interestingly, this effect was absent when TNBS was administered intraperitoneally, indicating a potential role of gut microbiota. Depletion of gut bacteria with antibiotics significantly attenuated the severity of TNBS-induced inflammation, oxidative damage, and tissue injury in the colon and kidneys. Mechanistic investigations using cultured colon epithelial cells and bone-marrow macrophages unveiled that TNBS induced cell oxidation, inflammation and injury, which was amplified by the bacterial component LPS and mitigated by thiol antioxidants. Importantly, in vivo administration of thiol-rich whey protein entirely prevented TNBS-induced colonic and kidney injury. Our findings suggest that gut bacteria significantly contribute to the initiation and progression of colitis and associated kidney injury, potentially through mechanisms involving LPS-induced exaggeration of oxidative cellular damage. Furthermore, our research highlights the potential of dietary thiol antioxidants as preventive and therapeutic interventions.

Transhiatal bilateral cervical approach for mediastinoscopy-assisted esophagectomy: A retrospective cohort study.

BACKGROUND: The McKeown minimally invasive esophagectomy (McMIE) procedure has various limitations, including surgical contraindications and a high rate of postoperative pulmonary complications. A novel mediastinoscopic esophagectomy procedure was described in this study by using esophageal invagination and a transhiatal and bilateral cervical approach (EITHBC). METHODS: According to the mode of operation, a total of 259 patients were divided into two groups, among which 106 underwent EITHBC and 153 underwent McMIE. The number of lymph nodes dissected, intraoperative outcomes, and postoperative outcomes were compared between the two groups of patients. RESULTS: The results revealed that the average number of resected lymph node in the EITHBC group was significantly higher in the recL106 and TbL106 stations (recL106: 1.75 vs. 1.51, p = 0.016, TbL106: 1.53 vs. 1.19, p = 0.016) and significantly lower in the 107 stations (1. 74 vs. 2. 07, p < 0.001) than in the McMIE group. The intraoperative blood loss in the EITHBC group was significantly lower than that in the McMIE group (63.30 vs. 80.45 mL, p < 0.001). The incidence of postoperative pulmonary complications in the EITHBC group was lower than that in the McMIE group (14.15% vs. 27.45%, p = 0.008). The incidence of recurrent laryngeal nerve paralysis in the EITHBC group was significantly higher than that in the McMIE group (26.41% vs. 10.46%, p = 0.003). CONCLUSION: Compared with the McMIE procedure, the EITHBC procedure has advantages in terms of removing the upper mediastinal lymph nodes and reducing postoperative pulmonary complications.

Analysis of gait characteristics and related factors in patients with Parkinson's disease based on wearable devices.

BACKGROUND: Postural instability and gait disorder dominant (PIGD) is one of the most common disabling symptoms of Parkinson's disease (PD), which seriously affects patients' quality of life. Therefore, it is essential to identify PIGD and develop targeted interventions to reduce the risk of PIGD in PD patients. AIM: This study aimed to investigate the gait characteristics of PD patients based on wearable devices and to establish a predictive model for their related influencing factors. METHODS: The retrospective medical records of patients from January 2020 to September 2023 were collected, including 159 patients with PD (divided into PIGD [n = 73] and non-PIGD [n = 86] groups) and 200 healthy patients (as the healthy control group). Information from social demographic data, a blood test, scale scores, gait analysis based on wearable devices, white matter lesions, and the Fazekas scale was extracted and analyzed. RESULTS: Compared with the healthy control group, the mean step length, mean rate, mean angular velocity, and step length were lower in the PD group, while the mean steps were higher in the turning test. The incidence of PIGD was 46% in PD patients, and PD patients with the non-tremor onset mode were more likely to develop PIGD than those with the tremor onset mode. Compared to the non-PIGD group, the PIGD group showed more serious gait problems in different experimental tasks and had a higher Hoehn and Yahr (H-Y) stage, Hamilton Anxiety Scale (HAMA) score, Hamilton Depression Scale score, periventricular white matter (PVWM) score, deep white matter score, and Fazekas scale score, but they had lower hemoglobin levels, D-dimer levels, Tinetti Balance scores, Tinetti Gait scores, Berg Balance Scale scores, and Mini-Mental State Examination (MMSE) scores. Logistic regression analysis showed that the MMSE score was negatively correlated with the occurrence of PIGD, while the HAMA score, H-Y stage, PVWM score, and non-tremor form of onset were positively correlated with the occurrence of PIGD CONCLUSION: The incidence of gait disorder in PD patients is higher than that in the normal population. Moreover, cognitive dysfunction, anxiety state, H-Y stage, PVWM score, and the non-tremor mode of onset can be considered independent risk factors for PIGD.

Quality Evaluation of Shexiang Tongxin Dropping Pill Based on HPLC Fingerprints Combined with HPLC-Q-TOF-MS/MS Method.

Shexiang Tongxin Dropping Pill (STP) is a composite formula of traditional Chinese medicine that is widely used for the treatment of cardiovascular diseases. It consists of seven medicinal extracts thereof or materials, including Bufonis venenum, synthetic Moschus, Panax ginseng, Bovis calculus artifactus, Bear bile powder, Salvia miltiorrhiza Bge and synthetic borneol. However, it is considerably difficult to evaluate the quality of STP due to its complex chemical compositions. This paper was designed to explore a comprehensive and systematic method combining fingerprints and chemical identification for quality assessment of STP samples. Twenty batches of STP samples were analyzed by high-performance liquid chromatography (HPLC) and high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry. Ten common peaks were detected by HPLC fingerprint similarity evaluation system. Meanwhile, 100 compounds belonging to 4 structural characteristics, including 23 bufadienolides, 36 organic acids, 34 saponins and 7 other types, were systematically identified as the basic components in STP. This study could be used for clarifying the multiple bioactive substances and developing a comprehensive quality evaluation method of STP.

Study of radiomics based on dual-energy CT for nuclear grading and T-staging in renal clear cell carcinoma.

INTRODUCTION: Clear cell renal cell carcinoma (ccRCC) is the most lethal subtype of renal cell carcinoma with a high invasive potential. Radiomics has attracted much attention in predicting the preoperative T-staging and nuclear grade of ccRCC. OBJECTIVE: The objective was to evaluate the efficacy of dual-energy computed tomography (DECT) radiomics in predicting ccRCC grade and T-stage while optimizing the models. METHODS: 200 ccRCC patients underwent preoperative DECT scanning and were randomized into training and validation cohorts. Radiomics models based on 70 KeV, 100 KeV, 150 KeV, iodine-based material decomposition images (IMDI), virtual noncontrasted images (VNC), mixed energy images (MEI) and MEI + IMDI were established for grading and T-staging. Receiver operating characteristic analysis and decision curve analysis (DCA) were performed. The area under the curve (AUC) values were compared using Delong test. RESULTS: For grading, the AUC values of these models ranged from 0.64 to 0.97 during training and from 0.54 to 0.72 during validation. In the validation cohort, the performance of MEI + IMDI model was optimal, with an AUC of 0.72, sensitivity of 0.71, and specificity of 0.70. The AUC value for the 70 KeV model was higher than those for the 100 KeV, 150 KeV, and MEI models. For T-staging, these models achieved AUC values of 0.83 to 1.00 in training and 0.59 to 0.82 in validation. The validation cohort demonstrated AUCs of 0.82 and 0.70, sensitivities of 0.71 and 0.71, and specificities of 0.80 and 0.60 for the MEI + IMDI and IMDI models, respectively. In terms of grading and T-staging, the MEI + IMDI model had the highest AUC in validation, with IMDI coming in second. There were statistically significant differences between the MEI + IMDI model and the 70 KeV, 100 KeV, 150 KeV, MEI, and VNC models in terms of grading (P < .05) and staging (P ≤ .001). DCA showed that both MEI + IDMI and IDMI models outperformed other models in predicting grade and stage of ccRCC. CONCLUSIONS: DECT radiomics models were helpful in grading and T-staging of ccRCC. The combined model of MEI + IMDI achieved favorable results.

Interfacial Electron Transfer in PbI2@Single-Walled Carbon Nanotube van der Waals Heterostructures for High-Stability Self-Powered Photodetectors.

Acquiring a deep insight into the electron transfer mechanism and applications of one-dimensional (1D) van der Waals heterostructures (vdWHs) has always been a significant challenge. Herein, through direct observation using aberration-corrected transmission electron microscopy (AC-TEM), we verify the stable formation of a high-quality 1D heterostructure composed of PbI2@single-walled carbon nanotubes (SWCNTs). The phenomenon of electron transfer between PbI2 and SWCNT is elucidated through spectroscopic investigations, including Raman and X-ray photoelectron spectroscopy (XPS). Electrochemical testing indicates the electron transfer and enduring stability of 1D PbI2 within SWCNTs. Moreover, leveraging the aforementioned electron transfer mechanism, we engineer self-powered photodetectors that exhibit exceptional photocurrent and a 3-order-of-magnitude switching ratio. Subsequently, we reveal its unique electron transfer behavior using Kelvin probe force microscopic (KPFM) tests. According to KPFM, the average surface potential of SWCNTs decreases by 80.6 mV after filling. Theoretical calculations illustrate a charge transfer of 0.02 e per unit cell. This work provides an effective strategy for the in-depth investigation and application of electron transfer in 1D vdWHs.

Molecular Evaluation of the Effects of FLC Homologs and Coordinating Regulators on the Flowering Responses to Vernalization in Cabbage (Brassica oleracea var. capitata) Genotypes.

The flowering loci of cabbage must be understood to boost their productivity. In this study, to clarify the flowering mechanisms of cabbage, we examined the three flowering repressors BoFLC1, 2 and 3, and the flowering regulators BoGI, BoCOOLAIR, and BoVIN3 of early (CAB1), middle (CAB3), and late (CAB5) flowering cabbage genotypes. Analysis of allele-specifically amplified genomic DNA and various sequence alignments demonstrated that maximal insertions and deletions influenced cabbage flowering behavior, notably in CAB3 and CAB5. Phylogenetic studies showed that BoFLC1, 2, and 3 in the CAB1, 3, and 5 genotypes had the highest homologies to other Brassica species, with CAB3 and 5 the most similar. Although CAB3 and CAB5 have comparable genetic patterns, flowering repressors and flowering regulators were investigated individually with and without vernalization to determine their minor flowering differences. The expression investigation revealed that vernalized CAB5 downregulated all BoFLC genes compared to CAB3 and, in contrast, CAB3 exhibited upregulated BoCOOLAIR. We hypothesized that the CAB3 BoFLC locus' additional insertions may have led to BoCOOLAIR overexpression and BoFLC downregulation. This study sheds light on cabbage genotypes-particularly those of CAB1 and CAB5-and suggests that structural variations in BoFLC2 and 3 bind flowering regulators, such as COOLAIR, which may affect cabbage flowering time.

Prefrontal projections modulate recurrent circuitry in the insular cortex to support short-term memory.

Short-term memory (STM) maintains information during a short delay period. How long-range and local connections interact to support STM encoding remains elusive. Here, we tackle the problem focusing on long-range projections from the medial prefrontal cortex (mPFC) to the anterior agranular insular cortex (aAIC) in head-fixed mice performing an olfactory delayed-response task. Optogenetic and electrophysiological experiments reveal the behavioral importance of the two regions in encoding STM information. Spike-correlogram analysis reveals strong local and cross-region functional coupling (FC) between memory neurons encoding the same information. Optogenetic suppression of mPFC-aAIC projections during the delay period reduces behavioral performance, the proportion of memory neurons, and memory-specific FC within the aAIC, whereas optogenetic excitation enhances all of them. mPFC-aAIC projections also bidirectionally modulate the efficacy of STM-information transfer, measured by the contribution of FC spiking pairs to the memory-coding ability of following neurons. Thus, prefrontal projections modulate insular neurons' functional connectivity and memory-coding ability to support STM.

The Value of Dual-Energy Computed Tomography-Based Radiomics in the Evaluation of Interstitial Fibers of Clear Cell Renal Carcinoma.

OBJECTIVE: We investigated the potential of dual-energy computed tomography (DECT) radiomics in assessing cancer-associated fibroblasts in clear cell renal carcinoma (ccRCC). METHODS: A retrospective analysis was conducted on 132 patients with ccRCC. The arterial and venous phase iodine-based material decomposition images (IMDIs), virtual non-contrast images, 70 keV, 100 keV, and 150 keV virtual monoenergetic images, and mixed energy images (MEIs) were obtained from the DECT datasets. On the Radcloud platform, radiomics feature extraction, feature selection, and model establishment were performed. Seven radiomics models were established using the support vector machine. The predictive performance was evaluated by utilizing receiver operating characteristic and the area under the curve (AUC) was calculated. Nomograms were constructed. RESULTS: The combined model demonstrated high efficiency in evaluating pseudocapsule thickness with AUC, specificity, and sensitivity of 0.833, 0.870, and 0.750, respectively in the validation set, surpassing those of other models. The precision, F1-score, and Youden index were also higher for the combined model. For evaluating the number of collagen fibers, the combined model exhibited the highest AUC (0.741) among all models, with a specificity of 0.830 and a sensitivity of 0.330. The AUC in the 150 kv model and IMDI model were slightly lower than those in the combined model (0.728 and 0.710, respectively), with corresponding sensitivity and specificity of 0.560/0.780 and 0.670/0.830. The nomogram exhibited that Rad-score had good prediction efficiency. CONCLUSION: DECT radiomics features have significant value in evaluating the interstitial fibers of ccRCC. The combined model of IMDI + MEI exhibits superior performance in assessing the thickness of the pseudocapsule, while the combined, 150 keV, and IMDI models demonstrate higher efficacy in evaluating collagen fiber number. Radiomics, combined with imaging features and clinical features, has excellent predictive performance. These findings offer crucial support for the clinical diagnosis, treatment, and prognosis of ccRCC and provide valuable insights into the application of DECT.

Insight into Multiphase Interlayer Molecular Packing and Stepwise Phase Transition in 4-(Phenylazo)benzoate Anion-Intercalated Layered Zinc Hydroxide.

The properties of layered intercalation hybrids are closely related to interlayer molecular packing. To develop functional intercalation hybrids, it is essential to gain deep insights into interlayer molecular packing. This work reports a new comprehensive insight into the controllable multiphase interlayer molecular packing in 4-(phenylazo)benzoate anion-intercalated layered zinc hydroxide (LZH-4-PAB intercalation hybrids). The new insight breaks up the general understanding that the interlayer molecular packing of anions is usually single-phase, lacking diversity and controllability. Furthermore, it uncovers an interesting stepwise rather than the generally expected continuous phase transition of the interlayer molecular packing. The intercalated 4-PAB anions initially organize into the horizontal monolayer packing (θ = 0°, Phase I), which stepwise transforms to the tilted interdigitated antiparallel bilayer packing (θ ≈ 50°, Phase II) along with an increased intercalation loading and eventually to the vertical interdigitated antiparallel bilayer packing (θ = 90°, Phase III). The LZH-4-PAB hybrids exhibited a greatly enhanced interlayer molecular packing-dependent UV-vis absorption. This study provides helpful guidance for developing property-tailored intercalation hybrids. It may attract new interest in more layered intercalation hybrids. New and rich intercalation chemistry might be discovered in more functional intercalation hybrids beyond the 4-PAB anion-intercalated layered zinc hydroxide.

Penisimplicins A and B: Novel Polyketide-Peptide Hybrid Alkaloids from the Fungus Penicillium simplicissimum JXCC5.

In this study, two previously undescribed nitrogen-containing compounds, penisimplicins A (1) and B (2), were isolated from Penicillium simplicissimum JXCC5. The structures of 1 and 2 were elucidated on the basis of comprehensive spectroscopic data analysis, including 1D and 2D NMR and HRESIMS data. The absolute configuration of 2 was determined by Marfey's method, ECD calculation, and DP4+ analysis. Both structures of 1 and 2 feature an unprecedented manner of amino acid-derivatives attaching to a polyketide moiety by C-C bond. The postulated biosynthetic pathways for 1 and 2 were discussed. Additionally, compound 1 exhibited significant acetylcholinesterase inhibitory activity, with IC50 values of 6.35 µM.

Utility of enteral nutrition via percutaneous transhepatic cholangiography drainage catheterization in late-stage malignant obstructive jaundice.

Objective: The purpose of this study was to explore the clinical benefits of establishing an enteral nutrition (EN) pathway via percutaneous transhepatic cholangiography drainage (PTCD) catheterization in patients with late-stage malignant obstructive jaundice (MOJ).Methods: We selected 30 patients diagnosed as having late-stage MOJ with malnutrition. A dual-lumen biliary-enteral nutrition tube was placed via PTCD along with a biliary stent implantation. Postoperative EN was provided, and we observed the time taken for tube placement, its success rate, complications, and therapeutic efficacy.Results: Tube placement was successful in all 30 patients with an average procedural time of 5.7 ± 1.4 min with no tube placement complications. Compared to preoperative measures, there was a significant improvement in postoperative jaundice reduction and nutritional indicators one month after the procedure (p < 0.05). Post-placement complications included tube perileakage in 5 cases, entero-biliary reflux in 4 cases, tube blockage in 6 cases, tube displacement in 4 cases, accidental tube removal in 3 cases, and tube replacement due to degradation in 8 cases, with tube retention time ranging from 42 to 314 days, averaging 124.7 ± 37.5 days. All patients achieved the parameters for effective home-based enteral nutrition with a noticeable improvement in their quality of life.Conclusion: In this study, we found that the technique of establishing an EN pathway via PTCD catheterization was minimally invasive, safe, and effective; the tube was easy to maintain; and patient compliance was high. It is, thus, suitable for long-term tube retention in patients with late-stage MOJ.

Direct α-Arylation of Benzo[b]furans Catalyzed by a Pd3 Cluster.

As an interim paradigm for the catalysts between those based on more conventional mononuclear molecular Pd complexes and Pdn nanoparticles widely used in organic synthesis, polynuclear palladium clusters have attracted great attention for their unique reactivity and electronic properties. However, the development of Pd cluster catalysts for organic transformations and mechanistic investigations is still largely unexploited. Herein, we disclose the use of trinuclear palladium (Pd3Cl) species as an active catalyst for the direct C-H α-arylation of benzo[b]furans with aryl iodides to afford 2-arylbenzofurans in good yields under mild conditions. With this method, broad substrate adaptability was observed, and several drug intermediates were synthesized in high yields. Mechanistic studies indicated that the Pd3 core most likely remained intact throughout the reaction course.

Enantioselective Total Synthesis of (-)-Daphenylline.

A concise enantioselective total synthesis of (-)-daphenylline, a hexacyclic Daphniphyllum alkaloid with a unique benzene ring, was achieved in 14 steps. The synthesis commences with two chiral stereocenters, C2 and C18, readily installed via Carreira's Ir/amine dual-catalyzed allylation. The allylic bridgehead amine 6 was rapidly prepared through Wickens' photoredox-catalyzed hydrocarboxylation of olefin and CuBr2-catalyzed α-amination of ketone. The tetracycle 4 was formed via Pd-catalyzed reductive Heck reaction or, more concisely, by Krische's Rh-catalyzed reductive 1,6-enyne cyclization. In this synthesis, newly reported Wickens' photoredox-catalyzed hydrocarboxylation was used twice, and Friedel-Crafts acylation thrice.