MuCoCP: a priori chemical knowledge-based multimodal contrastive learning pre-trained neural network for the prediction of cyclic peptide membrane penetration ability.

MOTIVATION: There has been a burgeoning interest in cyclic peptide therapeutics due to their various outstanding advantages and strong potential for drug formation. However, it is undoubtedly costly and inefficient to use traditional wet lab methods to clarify their biological activities. Using artificial intelligence instead is a more energy-efficient and faster approach. MuCoCP aims to build a complete pre-trained model for extracting potential features of cyclic peptides, which can be fine-tuned to accurately predict cyclic peptide bioactivity on various downstream tasks. To maximize its effectiveness, we use a novel data augmentation method based on a priori chemical knowledge and multiple unsupervised training objective functions to greatly improve the information-grabbing ability of the model. RESULTS: To assay the efficacy of the model, we conducted validation on the membrane-permeability of cyclic peptides which achieved an accuracy of 0.87 and R-squared of 0.503 on CycPeptMPDB using semi-supervised training and obtained an accuracy of 0.84 and R-squared of 0.384 using a model with frozen parameters on an external dataset. This result has achieved state-of-the-art, which substantiates the stability and generalization capability of MuCoCP. It means that MuCoCP can fully explore the high-dimensional information of cyclic peptides and make accurate predictions on downstream bioactivity tasks, which will serve as a guide for the future de novo design of cyclic peptide drugs and promote the development of cyclic peptide drugs. AVAILABILITY AND IMPLEMENTATION: All code used in our proposed method can be found at https://github.com/lennonyu11234/MuCoCP.

Hypericin-Loaded Carbon Nanohorn Hybrid for Combined Photodynamic and Photothermal Therapy in Vivo.

Photodynamic therapy (PDT) of hypericin (Hyp) is hampered by poor water solubility and photostability. Incorporation of photosensitizers into nanocarriers has been designed to solve these issues. Herein, SWNH-Hyps nanohybrids were first fabricated by loading hypericin on the surface of single-walled carbon nanohorns (SWNHs) through ??? interaction and exhibited high solubility and stability in aqueous water. SWNH-Hyps could be utilized for a single platform for cancer therapy because it could simultaneously generate enough reactive oxygen species and hyperthermia using light irradiation. Moreover, the SWNHs not only improved water solubility, photostability, and therapy effects of Hyp but also protected it from light degradation. SWNH-Hyps could effectively ablate 4T1 cells by photodynamic/photothermal synergistic therapy upon 590 and 808 nm light irradiations compared with PDT. Furthermore, remarkable tumor cell death as well as tumor growth inhibition was proved via photothermal therapy and PDT of SWNH-Hyps under 590 and 808 nm light irradiations, which demonstrated that synergistic anticancer ability of SWNH-Hyps was better than that of free Hyp in vivo. Such a simple and facile adsorption method improved water solubility of Hyp and then enhanced its therapy effect, which displays that SWNHs can be hopefully used in medicines in the future.

Impact of enhanced recovery after surgery on postoperative recovery after joint arthroplasty: results from a systematic review and meta-analysis.

STUDY DESIGN: Systematic review with meta-analysis. OBJECTIVES: To evaluate the effects of enhanced recovery after surgery (ERAS) on the postoperative recovery of patients who underwent total hip arthroplasty (THA) or total knee arthroplasty (TKA). METHODS: The PubMed, Embase, Cochrane and ISI Web of Science databases were searched to identify literature including randomised controlled trials (RCTs), cohort studies and case-control studies through 2 May 2018. The analysed outcomes were mortality rate, transfusion rate, range of motion (ROM), 30-day readmission rate, postoperative complication rate and in-hospital length of stay (LOS). RESULTS: A total of 25 studies involving 16 699 patients met the inclusion criteria and were included in the meta-analysis. Compared with conventional care, ERAS was associated with a significant decrease in mortality rate (relative risk (RR) 0.48, 95% CI 0.27 to 0.85), transfusion rate (RR 0.43, 95% CI 0.37 to 0.51), complication rate (RR 0.74, 95% CI 0.62 to 0.87) and LOS (mean difference (MD) -2.03, 95% CI -2.64 to -1.42) among all included trials. However, no significant difference was found in ROM (MD 7.53, 95% CI -2.16 to 17.23) and 30-day readmission rate (RR 0.86, 95% CI 0.56 to 1.30). There was no significant difference in complications of TKA (RR 0.84, 95% CI 0.34 to 2.06) and transfusion rate in RCTs (RR 0.66, 95% CI 0.15 to 2.88) between the ERAS group and the control group. CONCLUSIONS: This meta-analysis showed that ERAS significantly reduced the mortality rate, transfusion rate, incidence of complications and LOS of patients undergoing TKA or THA. However, ERAS did not show a significant impact on ROM and 30-day readmission rate. Complications after hip replacement are less than those of knee replacement, and the young patients recover better. LEVEL OF EVIDENCE: Level 1.

Selective Probing of Gaseous Ammonia Using Red-Emitting Carbon Dots Based on an Interfacial Response Mechanism.

Solid-state fluorescence sensing is one of the most appealing detection techniques because of its simplicity and convenience in practical operation. Herein, we report the development of a red-emitting carbon dots (RCDs)-based material as a solid-state fluorescence sensor for the selective probing of gaseous ammonia. The RCDs were prepared by a low-cost, one-step carbonization method using sugar cane bagasse as the carbon precursor. The pristine RCDs were then directly coated on polyvinylidene fluoride membrane to produce a new fluorescence sensor capable of selectively distinguishing toxic gaseous ammonia from other analyte vapors through sensitive fluorescence quenching with a low detection limit. More importantly, the interfacial response mechanism occurring on the surface of the RCDs has been studied by X-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy, and Raman measurements. The results indicate that fluorescence quenching in the RCDs might result from ammonia-induced Michael addition through insertion of N into the C=C group and deprotonation of the carboxyl group. To the best of our knowledge, this is the first report that provides clear insight into the mechanism of surface chemistry on CDs in the solid state.

Perioperative fluid management for adult cardiac surgery: network meta-analysis pooling on twenty randomised controlled trials.

BACKGROUND: The aim of this study was to evaluate colloids and crystalloids used in perioperative fluid therapy for cardiac surgery patients to further investigate the optimal management strategies of different solutions. METHOD: RCTs about adult surgical patients allocated to receive perioperative fluid therapy for electronic databases, including Ovid MEDLINE, EMBase, and Cochrane Central Register of Controlled Trials, were searched up to February 15, 2023. RESULTS: None of the results based on network comparisons, including mortality, transfuse PLA, postoperative chest tube output over the first 24 h following surgery, and length of hospital stay, were statistically significant. Due to the small number of included studies, the results, including acute kidney injury, serum creatinine, serum microglobulin, and blood urea nitrogen, are from the direct comparison. For transfusion of RBCs, significant differences were observed in the comparisons of 3% gelatine vs. 6% HES 200/0.5, 4% albumin vs. 5% albumin, 4% gelatine vs. 5% albumin, 5% albumin vs. 6% HES 200/0.5, and 6% HES 130/0.4 vs. 6% HES 200/0.5. In transfusion of FFP, significant differences were observed in comparisons of 3% gelatine vs. 4% gelatine, 3% gelatine vs. 6% HES 200/0.5, 5% albumin vs. 6% HES 200/0.5, 4% gelatine vs. 5% albumin, 4% gelatine vs. 6% HES 200/0.4, and 6% HES 130/0.4 vs. 6% HES 200/0.5. For urinary output at 24 h after surgery, the results are deposited in the main text. CONCLUSION: This study showed that 3% gelatin and 5% albumin can reduce the transfuse RBC and FFP. In addition, the use of hypertonic saline solution can increase urine output, and 5% albumin and 6% HES can shorten the length of ICU stay. However, none of the perioperative fluids showed an objective advantage in various outcomes, including mortality, transfuse PLA, postoperative chest tube output over the first 24 h following surgery, and length of hospital stay. The reliable and sufficient evidences on the injury of the kidney, including acute kidney injury, serum creatinine, serum microglobulin, and blood urea nitrogen, was still lacking. In general, perioperative fluids had advantages and disadvantages, and there were no evidences to support the recommendation of the optimal perioperative fluid for cardiac surgery.

Pro-inflammatory diets promote the formation of hyperuricemia.

Background: Hyperuricemia, as a very prevalent chronic metabolic disease with increasing prevalence year by year, poses a significant burden on individual patients as well as on the global health care and disease burden, and there is growing evidence that it is associated with other underlying diseases such as hypertension and cardiovascular disease. The association between hyperuricemia and dietary inflammatory index (DII) scores was investigated in this study. Methods: This study enrolled 13, 040 adult subjects (aged ≥ 20 years) from the US National Health and Nutrition Survey from 2003 to 2018. The inflammatory potential of the diet was assessed by the DII score, and logistic regression was performed to evaluate the relationship between the DII score and the development of hyperuricemia; subgroup analyses were used to discuss the influence of other factors on the relationship. Results: Participants in the other quartiles had an increased risk of hyperuricemia compared to those in the lowest quartile of DII scores. Stratification analyses stratified by body mass index (BMI), sex, hypertension, drinking, diabetes, education level and albumin-creatinine-ratio (ACR) revealed that the DII score was also associated with the risk of hyperuricemia (P<0.05). There was an interaction in subgroup analysis stratified by sex, age, and hypertension (P for interaction <0.05). The results showed a linear-like relationship between DII and hyperuricemia, with a relatively low risk of developing hyperuricemia at lower DII scores and an increased risk of developing hyperuricemia as DII scores increased. Conclusions: This study showed that the risk of hyperuricemia increased at slightly higher DII scores (i.e., with pro-inflammatory diets), but not significantly at lower levels (i.e., with anti-inflammatory diets). The contribution of the DII score to the development of hyperuricemia increased with higher scores. The relationship between inflammatory diets and hyperuricemia requires more research on inflammation, and this study alerts the public that pro-inflammatory diets may increase the risk of developing hyperuricemia.

Circular RNA circ_0008360 Inhibits the Proliferation, Migration, and Inflammation and Promotes Apoptosis of Fibroblast-Like Synoviocytes by Regulating miR-135b-5p/HDAC4 Axis in Rheumatoid Arthritis.

Circular RNAs (circRNAs) have been demonstrated to play crucial roles in the development and progression of many diseases, including rheumatoid arthritis (RA). However, the functions and molecular mechanism of circ_0008360 in RA remain unclear. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to determine the expression of circ_0008360, microRNA-135b-5p (miR-135b-5p), and histone deacetylase 4 (HDAC4). Cell Counting Kit-8 (CCK-8) assay, wound healing assay, and flow cytometry analysis were performed to assess cell proliferation, migration, and apoptosis, respectively. Inflammatory response was evaluated by enzyme-linked immunosorbent assay (ELISA). The interaction between miR-135b-5p and circ_0008360 or HDAC4 was predicted by bioinformatics analysis and verified by dual-luciferase reporter and RNA Immunoprecipitation (RIP) and RNA pull-down assays. Western blot assay was used to detect the protein expression of HDAC4 and proliferating cell nuclear antigen (PCNA). The expression of circ_0008360 was downregulated in RA synovial tissues and RA fibroblast-like synoviocytes (RA-FLSs). Circ_0008360 suppressed the proliferation, migration, and inflammation and promoted apoptosis of RA-FLSs, and circ_0008360 knockdown showed opposite effects. Moreover, miR-135b-5p was a direct target of circ_0008360, and miR-135b-5p could reverse the effects of circ_0008360 on proliferation, migration, inflammation, and apoptosis in RA-FLSs. Furthermore, HDAC4 was a downstream target of miR-135b-5p, and miR-135b-5p accelerated the proliferation, migration, and inflammation and suppressed apoptosis of RA-FLSs by targeting HDAC4. In addition, circ_0008360 positively regulated HDAC4 expression by sponging miR-135b-5p. Circ_0008360 inhibited the proliferation, migration, and inflammation and facilitated apoptosis of RA-FLSs by sponging miR-135b-5p and upregulating HDAC4, providing a potential target for prevention and treatment of RA.

Multifunctional hyaluronic acid-derived carbon dots for self-targeted imaging-guided photodynamic therapy.

It is of vital importance to engineer the surface structures of carbon dots (CDs) to satisfy their practical biomedical applications, including imaging and treatment. In this work, one type of hyaluronic acid-derived CD (HA-CD) was synthesized via a facile one-step hydrothermal method using cancer cell-targeted HA as a precursor. The as-prepared HA-CDs were targeted actively toward CD44 receptor-overexpressing cancer cells because a partial HA structure remained on the HA-CD surface. Beyond this, HA-CDs can act as a novel photosensitizer, because they can generate O2˙- under 650 nm laser irradiation, and they also exhibit excellent blue photoluminescence emission. The in vitro results revealed that HA-CDs imaged selectively CD44-overexpressing cancer cells and inhibited their growth under 650 nm laser irradiation. Thus, HA-CDs can serve as a promising self-targeted imaging-guided photodynamic therapy (PDT) agent for cancer. The present research provides a promising new method to simply construct multifunctional CD-based targeted phototheranostic systems.