Case report: Near-fatal hypermagnesemia resulting from the use of Epsom salts in a patient with normal renal function.

Hypermagnesemia commonly occurs in patients with renal dysfunction. Diagnosing hypermagnesemia represents a challenge due to its rarity and the absence of routine monitoring of magnesium levels. Furthermore, the lack of awareness among clinicians regarding this uncommon condition frequently leads to delayed diagnoses. Few patients survive with a serum magnesium level exceeding 7 mmol/L. This article presents a case study of near-fatal hypermagnesemia resulting from the oral administration of Epsom salts in a patient with normal renal function. A 60-year-old female presented to the gastroenterology department on Oct. 6, 2023, with a 3-day history of black stools. She underwent subtotal gastrectomy in 2005 and has a stable history of nephrotic syndrome. To investigate the cause of her bleeding, electronic gastroscopy and colonoscopy were scheduled for Oct. 11, 2023. She experienced a sudden loss of consciousness 30 min after the ingestion of Epsom salts. The attending physician suspected a severe magnesium poisoning. She was promptly administered calcium gluconate, underwent tracheal intubation with ambu bag ventilation, and received early continuous renal replacement therapy (CRRT). Swift diagnosis and CRRT contributed to a reduction in her serum magnesium levels from an initial 8.71 mmol/L to 1.35 mmol/L, leading to a remarkable improvement in the toxic symptoms associated with hypermagnesemia. Subsequently, she was managed in the gastroenterology department, with gastroscopy revealing bleeding from the gastrointestinal anastomotic ulcer. Following conservative treatments including acid suppression, stomach protection, and hemostasis, her symptoms improved, and she was successfully discharged. This study aims to alert clinicians to the possibility of hypermagnesemia in individuals with normal renal function. Physicians should exercise caution when prescribing Epsom salts to patients with underlying gastrointestinal conditions. If necessary, alternative drug therapies may be considered to mitigate the risk of hypermagnesemia. Timely intervention is pivotal in averting life-threatening complications linked to hypermagnesemia.

Plate fixation of inferior ramus in pubis-ischium ramus improves mechanical stability in Tile B pelvic injures: a cadaveric biomechanical analysis and early clinical experience.

BACKGROUND: Management of inferior ramus of the pubis-ischium ramus remains controversial, and related research is sparse. The main intention of this study is to describe the biomechanical and clinical outcomes of pubis-ischium ramus fractures in Tile B pelvic injuries and to identify the feasibility and necessity of fixation of the inferior ramus of the pubis-ischium ramus. METHODS: This study comprised two parts: a biomechanical test and a retrospective clinical study. For the biomechanical tests, Tile B-type pelvic injuries were modeled in six cadaver specimens by performing pubis-ischium osteotomies and disruption of the anterior and interosseous sacroiliac ligaments. The superior and/or inferior rami of the pubis-ischium ramus were repaired with reconstruction plates and separated into three groups (A, B, and C). Specimens were placed in the standing position and were loaded axially with two-leg support for three cycles at 500 N. The displacements of sacroiliac joints at osteotomy were measured with Vernier calipers and compared using statistical software. To investigate the clinical outcomes of this technique, 26 patients were retrospectively analyzed and divided into a superior ramus fixation group (Group D) and a combined superior and inferior ramus of the pubis-ischium ramus fixation group (Group E). The main outcome measures were time of operation, blood loss, postoperative radiographic reduction grading, and functional outcomes. RESULTS: In the vertical loading test, Group E showed better pelvic ring stability than Group D (P < 0.05). However, the shift of the sacroiliac joints was almost identical among the three groups. In our clinical case series, all fractures in Group E achieved bony union. Group E demonstrated earlier weight-bearing functional exercise (2.54 ± 1.45 vs 4.77 ± 2.09; P = 0.004), earlier bony union (13.23 ± 2.89 vs 16.55 ± 3.11; P = 0.013), and better functional outcomes (89.77 ± 7.27 vs 82.38 ± 8.81; P = 0.028) than Group D. The incidence of sexual dysfunction was significantly lower in Group E than that in Group D (2/13 vs 7/13; P = 0.039). Bone nonunion occurred in two patients in Group D, and two patients in Group E had heterotopic ossification. None of the patients exhibited wound complications, infections, implant failures, or bone-implant interface failures. CONCLUSIONS: Fixation of the inferior ramus of a pubis-ischium ramus fracture based on conventional fixation of the anterior pelvic ring is mechanically superior in cadaveric Tile B pelvic injury and shows rapid recovery, good functional outcomes, and low incidence of complications.

Versatile Framework for Drug-Target Interaction Prediction by Considering Domain-Specific Features.

Predicting drug-target interactions (DTIs) is one of the crucial tasks in drug discovery, but traditional wet-lab experiments are costly and time-consuming. Recently, deep learning has emerged as a promising tool for accelerating DTI prediction due to its powerful performance. However, the models trained on limited known DTI data struggle to generalize effectively to novel drug-target pairs. In this work, we propose a strategy to train an ensemble of models by capturing both domain-generic and domain-specific features (E-DIS) to learn diverse domain features and adapt them to out-of-distribution data. Multiple experts were trained on different domains to capture and align domain-specific information from various distributions without accessing any data from unseen domains. E-DIS provides a comprehensive representation of proteins and ligands by capturing diverse features. Experimental results on four benchmark data sets in both in-domain and cross-domain settings demonstrated that E-DIS significantly improved model performance and domain generalization compared to existing methods. Our approach presents a significant advancement in DTI prediction by combining domain-generic and domain-specific features, enhancing the generalization ability of the DTI prediction model.

Machine Learning-Guided Prediction of Desalination Capacity and Rate of Porous Carbons for Capacitive Deionization.

Nowadays, capacitive deionization (CDI) has emerged as a prominent technology in the desalination field, typically utilizing porous carbons as electrodes. However, the precise significance of electrode properties and operational conditions in shaping desalination performance remains blurry, necessitating numerous time-consuming and resource-intensive CDI experiments. Machine learning (ML) presents an emerging solution, offering the prospect of predicting CDI performance with minimal investment in electrode material synthesis and testing. Herein, four ML models are used for predicting the CDI performance of porous carbons. Among them, the gradient boosting model delivers the best performance on test set with low root mean square error values of 2.13 mg g-1 and 0.073 mg g-1 min-1 for predicting desalination capacity and rate, respectively. Furthermore, SHapley Additive exPlanations is introduced to analyze the significance of electrode properties and operational conditions. It highlights that electrolyte concentration and specific surface area exert a substantially more influential role in determining desalination performance compared to other features. Ultimately, experimental validation employing metal-organic frameworks-derived porous carbons and biomass-derived porous carbons as CDI electrodes is conducted to affirm the prediction accuracy of ML models. This study pioneers ML techniques for predicting CDI performance, offering a compelling strategy for advancing CDI technology.

Heterointerface regulation of covalent organic framework-anchored graphene via a solvent-free strategy for high-performance supercapacitor and hybrid capacitive deionization electrodes.

Covalent organic frameworks (COFs) with customizable geometry and redox centers are an ideal candidate for supercapacitors and hybrid capacitive deionization (HCDI). However, their poor intrinsic conductivity and micropore-dominated pore structures severely impair their electrochemical performance, and the synthesis process using organic solvents brings serious environmental and cost issues. Herein, a 2D redox-active pyrazine-based COF (BAHC-COF) was anchored on the surface of graphene in a solvent-free strategy for heterointerface regulation. The as-prepared BAHC-COF/graphene (BAHCGO) nanohybrid materials possess high-speed charge transport offered by the graphene carrier and accelerated electrolyte ion migration within the BAHC-COF, allowing ions to effectively occupy ion storage sites inside BAHC. As a result, the BAHCGO//activated carbon asymmetric supercapacitor achieves a high energy output of 61.2 W h kg-1 and a satisfactory long-term cycling life. More importantly, BAHCGO-based HCDI possesses a high salt adsorption capacity (SAC) of 67.5 mg g-1 and excellent long-term desalination/regeneration stability. This work accelerates the application of COF-based materials in the fields of energy storage and water treatment.

Single-cell transcriptomics dissects the transcriptome alterations of hematopoietic stem cells in myelodysplastic neoplasms.

BACKGROUND: Myelodysplastic neoplasms (MDS) are myeloid neoplasms characterized by disordered differentiation of hematopoietic stem cells and a predisposition to acute myeloid leukemia (AML). The underline pathogenesis remains unclear. METHODS: In this study, the trajectory of differentiation and mechanisms of leukemic transformation were explored through bioinformatics analysis of single-cell RNA-Seq data from hematopoietic stem and progenitor cells (HSPCs) in MDS patients. RESULTS: Among the HSPC clusters, the proportion of common myeloid progenitor (CMP) was the main cell cluster in the patients with excess blasts (EB)/ secondary AML. Cell cycle analysis indicated the CMP of MDS patients were in an active proliferative state. The genes involved in the cell proliferation, such as MAML3 and PLCB1, were up-regulated in MDS CMP. Further validation analysis indicated that the expression levels of MAML3 and PLCB1 in patients with MDS-EB were significantly higher than those without EB. Patients with high expression of PLCB1 had a higher risk of transformation to AML. PLCB1 inhibitor can suppress proliferation, induce cell cycle arrest, and activate apoptosis of leukemic cells in vitro. CONCLUSION: This study revealed the transcriptomic change of HSPCs in MDS patients along the pseudotime and indicated that PLCB1 plays a key role in the transformation of MDS into leukemia.

Progress of lymphocyte activation gene 3 and programmed cell death protein 1 antibodies for cancer treatment: A review.

The application of immune checkpoint inhibitors has proven to be an effective treatment for cancer. Immune checkpoints such as programmed cell death protein 1/programmed cell death protein 1 ligand 1 (PD-1/PD-L1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), T-cell immunoglobulin-3 (TIM-3), T-cell immunoglobulin and ITIM domain (TIGIT), and lymphocyte activation gene-3 (LAG-3) have received extensive attention, and the efficacy of antibodies or inhibitors against these checkpoints (either alone or in combination) has been evaluated in many tumors. This paper provides a brief overview of the PD-1 and LAG-3 checkpoints, and then shifts focus to the combined use of PD-1 and LAG-3 antibodies in both in vivo and in vitro experiments. In the in vitro experiments, we examined the correlation between the expression and activation of these inhibitors on T cells, and also assessed toxicity in animals in preparation for in vivo experiments. The effects of the combined use of PD-1 and LAG-3 antibodies were then summarized in animal models of melanoma, MC38 carcinoma, and other tumors. In clinical studies, the combined application of these antibodies was assessed in patients with melanoma, colorectal, breast, and renal cell cancers, as well as other solid tumors. In general, the combination of PD-1 and LAG-3 antibodies has shown promising results in both in vivo and in vitro studies.

Exosomes promote pre-metastatic niche formation in colorectal cancer.

It is well known that colorectal cancer (CRC) has a high morbidity rate, a poor prognosis when metastasized, and a greatly shortened 5-year survival rate. Therefore, understanding the mechanism of tumor metastasis is still important. Based on the "seed and soil" theory, the concept of " premetastatic niche (PMN)" was introduced by Kaplan et al. The complex interaction between primary tumors and the metastatic organ provides a beneficial microenvironment for tumor cells to colonize at a distance. With further exploration of the PMN, exosomes have gradually attracted interest from researchers. Exosomes are extracellular vesicles secreted from cells that include various biological information and are involved in communication between cells. As a key molecule in the PMN, exosomes are closely related to tumor metastasis. In this article, we obtained information by conducting a comprehensive search across academic databases including PubMed and Web of Science using relevant keywords. Only recent, peer-reviewed articles published in the English language were considered for inclusion. This study aims to explore in depth how exosomes promote the formation of pre-metastatic microenvironment (PMN) in colorectal cancer and its related mechanisms.

GPNMB promotes peripheral nerve regeneration by activating the Erk1/2 and Akt pathways via binding Na+/K+-ATPase α1 in Schwann cells.

Glycoprotein non-metastatic melanoma protein B (GPNMB) is ubiquitously expressed and has protective effects on the central nervous system. In particular, it is also expressed in the peripheral nervous system (PNS) and upregulated after peripheral nerve injury. However, the role and underlying mechanism of GPNMB in the PNS, especially in peripheral nerve regeneration (PNR), are still unknown and need to be further investigated. In this study, recombinant human GPNMB (rhGPNMB) was injected into a sciatic nerve injury model. It was found that rhGPNMB facilitated the regeneration and functional recovery of the injured sciatic nerve in vivo. Moreover, it was also confirmed that GPNMB activated the Erk1/2 and Akt pathways via binding with Na+/K + -ATPase α1 (NKA α1) and promoted the proliferation and migration of Schwann cells (SCs) and their expression and secretion of neurotrophic factors and neural adhesion molecules in vitro. Our findings demonstrate that GPNMB facilitates PNR through activation of the Erk1/2 and Akt pathways in SCs by binding with NKA α1 and may be a novel strategy for PNR.

Mitochondrial-targeting and NIR-responsive Mn3O4@PDA@Pd-SS31 nanozymes reduce oxidative stress and reverse mitochondrial dysfunction to alleviate osteoarthritis.

Mitochondrial reactive oxygen species (mROS) play a crucial role in the process of osteoarthritis (OA), which may be a promising target for therapy of OA. In this study, novel mitochondrial-targeting and SOD-mimic Mn3O4@PDA@Pd-SS31 nanozymes with near-infrared (NIR) responsiveness and synergistic cascade to scavenge mROS were designed for the therapy of OA. Results showed that the nanozymes accelerated the release of Pd and Mn3O4 under NIR irradiation, exhibiting enhanced activities of SOD and CAT mimic enzymes with reversed mitochondrial dysfunction and promoted mitophagy to effectively scavenge mROS from chondrocytes, modulate the microenvironment of oxidative stress, and eventually inhibit the inflammatory response. Nanozymes were excreted in vivo through intestinal metabolic pathway and had good biocompatibility, effectively reducing the inflammatory response and relieving articular cartilage degeneration in OA joints, with a reduction of 93.7 % and 93.8 % in OARSCI scores for 4 and 8 weeks respectively. Thus, this study demonstrated that the mitochondria targeting and NIR responsive Mn3O4@PDA@Pd-SS31 nanozymes could efficiently scavenge mROS, repair damaged mitochondrial function and promote cartilage regeneration, which are promising for the treatment of OA in clinical applications.

Endothelial extracellular vesicles induce acute lung injury via follistatin-like protein 1.

Cardiopulmonary bypass has been speculated to elicit systemic inflammation to initiate acute lung injury (ALI), including acute respiratory distress syndrome (ARDS), in patients after cardiac surgery. We previously found that post-operative patients showed an increase in endothelial cell-derived extracellular vesicles (eEVs) with components of coagulation and acute inflammatory responses. However, the mechanism underlying the onset of ALI owing to the release of eEVs after cardiopulmonary bypass, remains unclear. Plasma plasminogen-activated inhibitor-1 (PAI-1) and eEV levels were measured in patients with cardiopulmonary bypass. Endothelial cells and mice (C57BL/6, Toll-like receptor 4 knockout (TLR4-/-) and inducible nitric oxide synthase knockout (iNOS-/-)) were challenged with eEVs isolated from PAI-1-stimulated endothelial cells. Plasma PAI-1 and eEVs were remarkably enhanced after cardiopulmonary bypass. Plasma PAI-1 elevation was positively correlated with the increase in eEVs. The increase in plasma PAI-1 and eEV levels was associated with post-operative ARDS. The eEVs derived from PAI-1-stimulated endothelial cells could recognize TLR4 to stimulate a downstream signaling cascade identified as the Janus kinase 2/3 (JAK2/3)-signal transducer and activator of transcription 3 (STAT3)-interferon regulatory factor 1 (IRF-1) pathway, along with iNOS induction, and cytokine/chemokine production in vascular endothelial cells and C57BL/6 mice, ultimately contributing to ALI. ALI could be attenuated by JAK2/3 or STAT3 inhibitors (AG490 or S3I-201, respectively), and was relieved in TLR4-/- and iNOS-/- mice. eEVs activate the TLR4/JAK3/STAT3/IRF-1 signaling pathway to induce ALI/ARDS by delivering follistatin-like protein 1 (FSTL1), and FSTL1 knockdown in eEVs alleviates eEV-induced ALI/ARDS. Our data thus demonstrate that cardiopulmonary bypass may increase plasma PAI-1 levels to induce FSTL1-enriched eEVs, which target the TLR4-mediated JAK2/3/STAT3/IRF-1 signaling cascade and form a positive feedback loop, leading to ALI/ARDS after cardiac surgery. Our findings provide new insight into the molecular mechanisms and therapeutic targets for ALI/ARDS after cardiac surgery.

CODD-Pred: A Web Server for Efficient Target Identification and Bioactivity Prediction of Small Molecules.

Target identification and bioactivity prediction are critical steps in the drug discovery process. Here we introduce CODD-Pred (COmprehensive Drug Design Predictor), an online web server with well-curated data sets from the GOSTAR database, which is designed with a dual purpose of predicting potential protein drug targets and computing bioactivity values of small molecules. We first designed a double molecular graph perception (DMGP) framework for target prediction based on a large library of 646 498 small molecules interacting with 640 human targets. The framework achieved a top-5 accuracy of over 80% for hitting at least one target on both external validation sets. Additionally, its performance on the external validation set comprising 200 molecules surpassed that of four existing target prediction servers. Second, we collected 56 targets closely related to the occurrence and development of cancer, metabolic diseases, and inflammatory immune diseases and developed a multi-model self-validation activity prediction (MSAP) framework that enables accurate bioactivity quantification predictions for small-molecule ligands of these 56 targets. CODD-Pred is a handy tool for rapid evaluation and optimization of small molecules with specific target activity. CODD-Pred is freely accessible at http://codd.iddd.group/.

Generic Interpretable Reaction Condition Predictions with Open Reaction Condition Datasets and Unsupervised Learning of Reaction Center.

Effective synthesis planning powered by deep learning (DL) can significantly accelerate the discovery of new drugs and materials. However, most DL-assisted synthesis planning methods offer either none or very limited capability to recommend suitable reaction conditions (RCs) for their reaction predictions. Currently, the prediction of RCs with a DL framework is hindered by several factors, including: (a) lack of a standardized dataset for benchmarking, (b) lack of a general prediction model with powerful representation, and (c) lack of interpretability. To address these issues, we first created 2 standardized RC datasets covering a broad range of reaction classes and then proposed a powerful and interpretable Transformer-based RC predictor named Parrot. Through careful design of the model architecture, pretraining method, and training strategy, Parrot improved the overall top-3 prediction accuracy on catalysis, solvents, and other reagents by as much as 13.44%, compared to the best previous model on a newly curated dataset. Additionally, the mean absolute error of the predicted temperatures was reduced by about 4 °C. Furthermore, Parrot manifests strong generalization capacity with superior cross-chemical-space prediction accuracy. Attention analysis indicates that Parrot effectively captures crucial chemical information and exhibits a high level of interpretability in the prediction of RCs. The proposed model Parrot exemplifies how modern neural network architecture when appropriately pretrained can be versatile in making reliable, generalizable, and interpretable recommendation for RCs even when the underlying training dataset may still be limited in diversity.

Neutrophil to Lymphocyte ratio as a predictor for immune-related adverse events in cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis.

Background: The use of immune checkpoint inhibitors (ICIs) in cancer treatment has led to an increase in immune-related adverse events (irAEs), which can cause treatment discontinuation and even fatal reactions. The purpose of this study was to evaluate the usefulness of the peripheral biomarker neutrophil to lymphocyte ratio (NLR) in predicting irAEs. Methods: A systematic search of databases was conducted to identify studies on the predictive value of NLR for irAEs. The standardized mean difference (SMD) was used to compare continuous NLR, while crude odds ratios (ORs) were calculated for categorized NLR if adjusted ORs and 95% confidence intervals (CIs) were not provided in the original study. Results: The meta-analysis included 47 studies with a total of 11,491 cancer patients treated with ICIs. The baseline continuous NLR was significantly lower in patients with irAEs compared to those without (SMD=-1.55, 95%CI=-2.64 to -0.46, P=0.006). Similarly, categorized NLR showed that lower baseline NLR was associated with increased irAEs (OR=0.55, 95%CI=0.41-0.73, P<0.001). Subgroup analysis revealed that the OR for predicting irAEs with NLR cut-off values of 3 and 5 was 0.4 and 0.59, respectively. Interestingly, increased baseline NLR was associated with a higher incidence of immune-related liver injury (OR=2.44, 95%CI=1.23-4.84, I2 = 0%, P=0.010). Conclusion: Our study suggests that lower baseline NLR is associated with a higher risk of overall irAEs. However, further studies are needed to determine the best cut-off value and explore the efficacy of NLR in predicting specific types of irAEs.

Real-World Effectiveness and Safety of Hydrogen Inhalation in Chinese Patients with Type 2 Diabetes: A Single-Arm, Retrospective Study.

Aim: To evaluate the real-life effectiveness and safety of Chinese patients with type 2 diabetes mellitus (T2DM) receiving hydrogen inhalation (HI) treatment as a supplementary treatment. Methods: This retrospective, multicenter, observational 6-months clinical study included T2DM patients maintaining HI, visited at 4 time points. The primary outcome is the mean change in glycated hemoglobin (HbA1c) at the end of the study compared to baseline. The secondary outcome is analyzing the mean change of fasting plasma glucose (FPG), weight, lipid profile, insulin dose and homeostasis model assessment. Linear regression and logistics regression are applied to evaluate the effect of HI after the treatment. Results: Of the 431 patients comprised, it is observed a significant decrease in HbA1c level (9.04±0.82% at baseline to 8.30±0.99% and 8.00±0.80% at the end, p<0.001), FPG (165.6±40.2 mg/dL at baseline to 157.1±36.3mg/dL and 143.6±32.3mg/dL at the end, p<0.001), weight (74.7±7.1kg at baseline to 74.8±10.0kg and 73.6±8.1kg at the end, p<0.001), insulin dose (49.3±10.8U/d at baseline to 46.7±8.0U/d and 45.2±8.7U/d, p<0.001). The individuals in subgroup with higher baseline HbA1c and longer daily HI time duration gain greater HbA1c decrease after 6 months. Linear regression shows that higher baseline HbA1c level and shorter diabetes duration are significantly in relation to greater HbA1c reduction. Logistics regression reveals that lower weight is associated with a higher possibility of reaching HbA1c<7%. The most common adverse event is hypoglycemia. Conclusion: HI therapy significantly improves glycemic control, weight, insulin dose, lipid metabolism, ß-cell function and insulin resistance of patients with type 2 diabetes after 6 months. Higher baseline HbA1c level and shorter diabetes duration is related to greater clinical response to HI.

A propensity score-matched analysis of neoadjuvant chemoimmunotherapy versus surgery alone for locally advanced esophageal squamous cell carcinoma.

BACKGROUND: The aim of this study was to evaluate the safety, efficacy, and oncologic outcomes of neoadjuvant immunotherapy combined with chemotherapy (NICT) group and surgery alone group in the treatment of patients with locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: A series of 232 consecutive patients who underwent surgery with or without NICT from June 2019 to August 2022 were evaluated. We performed propensity score matching between the NICT and surgery alone groups on the basis of estimated propensity scores for each patient. RESULTS: After propensity score matching, data of 137 patients with clinical stages II-IV ESCC, including 85 receiving surgery alone and 52 receiving NICT, were analyzed. Compared with the surgery alone group (301.7 ± 94.4 min), the operation time was significantly longer in the NICT group (333.4 ± 79.7 min). However, there was no significant difference between the two groups in the postoperative complications, intraoperative blood loss, thoracic fluid volume, chest tube duration, lengths of intensive care unit stay and postoperative hospitalization. Additionally, 90-day mortality rate and 30-day readmission were similar in both groups. CONCLUSIONS: Overall, NICT followed by esophagectomy appears to be safe and feasible for locally advanced ESCC. However, further multicenter prospective clinical trials are needed to validate our results.

Improving drug-target affinity prediction via feature fusion and knowledge distillation.

Rapid and accurate prediction of drug-target affinity can accelerate and improve the drug discovery process. Recent studies show that deep learning models may have the potential to provide fast and accurate drug-target affinity prediction. However, the existing deep learning models still have their own disadvantages that make it difficult to complete the task satisfactorily. Complex-based models rely heavily on the time-consuming docking process, and complex-free models lacks interpretability. In this study, we introduced a novel knowledge-distillation insights drug-target affinity prediction model with feature fusion inputs to make fast, accurate and explainable predictions. We benchmarked the model on public affinity prediction and virtual screening dataset. The results show that it outperformed previous state-of-the-art models and achieved comparable performance to previous complex-based models. Finally, we study the interpretability of this model through visualization and find it can provide meaningful explanations for pairwise interaction. We believe this model can further improve the drug-target affinity prediction for its higher accuracy and reliable interpretability.

The comparison of manual and mechanical anastomosis after total pharyngolaryngoesophagectomy.

Background: Total pharyngolaryngoesophagectomy (TPLE) is considered as a curative treatment for hypopharynx cancer and cervical esophageal carcinomas (HPCECs). Traditional pharyngo-gastric anastomosis is usually performed manually, and postoperative complications are common. The aim of this study was to introduce a new technique for mechanical anastomosis and to evaluate perioperative outcomes and prognosis. Methods: From May 1995 to Nov 2021, a series of 75 consecutive patients who received TPLE for a pathological diagnosis of HPCECs at Sun Yat-sen Memorial Hospital were evaluated. Mechanical anastomosis was performed in 28 cases and manual anastomosis was performed in 47 cases. The data from these patients were retrospectively analyzed. Results: The mean age was 57.6 years, and 20% of the patients were female. The rate of anastomotic fistula and wound infection in the mechanical group were significantly lower than that in the manual group. The operation time, intraoperative blood loss and postoperative hospital stays were significantly higher in the manual group than that in the mechanical group. The R0 resection rate and the tumor characteristics were not significantly different between groups. There was no significant difference in overall survival and disease-free survival between the two groups. Conclusion: The mechanical anastomosis technology adopted by this study was shown to be a safer and more effective procedure with similar survival comparable to that of manual anastomosis for the HPCECs patients.

Feeding Strategies for Adapting Lake Sturgeon (Acipenser fulvescens) Larvae to Formulated Diets at Early Life Stages.

Cost-effective feeding management is required to support conservation hatcheries for lake sturgeon (Acipenser fulvescens), an ecologically important species in the Great Lakes region. This study investigated an approach to transition lake sturgeon larvae from live feed (Artemia) to formulated feed and its effect on growth performance, survival, and response to acute hypoxia stress. The first experiment showed that sturgeon had similar (p > 0.05) growth and survival when fed Artemia or the combined feeding of Artemia with the commercial diet (crude protein, 551 g/kg diet). Feeding solely on the commercial or lab-made (crude protein, 491 g/kg diet) diet significantly reduced growth and survival (p < 0.05). In the second experiment, the growth performance of sturgeon (14 days post-hatch, DPH) fed with either Artemia only or combined feeding different feeding durations of two, three, and four weeks followed by a complete transition to the commercial diet. At the end of six weeks, the 3- and 4-week combined feeding periods resulted in significantly higher body weight and survival compared to the 2-week combined and the Artemia only feeding treatments. In the last experiment, sturgeons (27 DPH) were fed only with Artemia or combined feeding of Artemia with the commercial diet for four weeks followed by the complete transition to the commercial diet for two weeks. Eighteen fish from each treatment were investigated the response to acute hypoxic conditions (gradual decrease in dissolved oxygen level from 8 to 2.3 mg/L at the rate of 1 mg/L per hour). When the dissolved oxygen was between 3 and 4 mg/L, the mortality rate of the combination-fed sturgeon (11.7%) was significantly lower than those fed only Artemia (83.3%). These results clearly demonstrate that a commercial diet can partially replace Artemia at early life stages to improve growth, survival, and hypoxia tolerance and thus its co-feeding with Artemia is recommended.