Challenges of enzyme therapy: Why two players are better than one.

Enzyme-based therapy has garnered significant attention for its current applications in various diseases. Despite the notable advantages associated with the use of enzymes as therapeutic agents, that could have high selectivity, affinity, and specificity for the target, their application faces challenges linked to physico-chemical and pharmacological properties. These limitations can be addressed through the encapsulation of enzymes in nanoplatforms as a comprehensive solution to mitigate their degradation, loss of activity, off-target accumulation, and immunogenicity, thus enhancing bioavailability, therapeutic efficacy, and circulation time, thereby reducing the number of administrations, and ameliorating patient compliance. The exploration of novel nanomedicine-based enzyme therapeutics for the treatment of challenging diseases stands as a paramount goal in the contemporary scientific landscape, but even then it is often not enough. Combining an enzyme with another therapeutic (e.g., a small molecule, another enzyme or protein, a monoclonal antibody, or a nucleic acid) within a single nanocarrier provides innovative multidrug-integrated therapy and ensures that both the actives arrive at the target site and exert their therapeutic effect, leading to synergistic action and superior therapeutic efficacy. Moreover, this strategic approach could be extended to gene therapy, a field that nowadays has gained increasing attention, as enzymes acting at genomic level and nucleic acids may be combined for synergistic therapy. This multicomponent therapeutic approach opens opportunities for promising future developments. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies.

The Synergistic Anti-tumor Effects of Evodiamine based on Animal Model Experiments: A Systematic Review and Meta-analysis.

BACKGROUND: Evodiamine (EVO) is an alkaloid extracted from the dried and nearly ripe fruits of Euodia rutaecarpa and used as an anti-cancer, anti-inflammatory and anti-obesity agent. However, robust evidence of preclinical experiments has been lacking so far. Therefore, the purpose of this article was to investigate the effect of EVO in combination with other treatments on tumors in animal experiments. METHODS: A systematic review and meta-analysis were conducted to assess the anti-tumor effect of evodiamine-combined therapy. The search engine and electronic databases included PubMed, Scopus, China Knowledge Resource Integrated Database (CNKI), and SinoMed. The research method was based on the PRISMA checklist. RESULTS: A total of 7 studies and 108 animals were included. As a result, EVO combined therapy was found to be more effective than EVO monotherapy. The SMD was -25.64(95% CI: -5.77 -3.13) in tumor growth. In tumor weight, the SMD was -8.91(95% CI: -16.37, -1.44). CONCLUSION: EVO has the potential to alleviate the toxicity of chemotherapeutic agents, which increases the translatability to the clinical situation.

The Role of Exercise: Physical Fitness Changes Caused by Hypocaloric Diet and Exercise in Men Who Are Overweight.

OBJECTIVE: There is evidence showing the effect of hypocaloric diet and increasing physical activity on weight loss. However, the effect of these factors on body composition and functional capacity remains unclear. Also, it is not clear which type of exercise (aerobic, resistance) has effective health benefits for men who are overweight. The aim of this study is to investigate whether a 12-week combined exercise or walking intervention combined with a hypocaloric diet provides improvements in body composition and functional capacity of men who are overweight compared to those who do not exercise. METHODS: 60 healthy adult men who are overweight were randomized and divided into 3 groups: 1: Hypocaloric Diet + Combined Exercise; 2: Hypocaloric Diet + Walking; 3: Hypocaloric Diet. The exercise groups were trained for 12 wk, 3 days a week and 60 min (60 min\3 days\12 wk). Body composition was determined with Bioelectrical Impedance Analysis (BIA) device, strength parameters with MicroFet 2, functional capacity with 6-min walking test. RESULTS: Improvement was observed in all groups at the end of 12 wk. The greatest improvement was in the combined exercise group. While the values of the combined exercise group increased in Skeletal Muscle Mass, there was a decline in the walking and non-exercising group. Basal Metabolism was maintained in combined exercise, but a decrease occurred in the non-exercising group. Muscle force increased in combined exercise; however, it was maintained in the legs in the walking group. Cardiorespiratory fitness was at best level in walking group, but there was no difference between combined exercise. CONCLUSIONS: As a result, a hypocaloric diet without an exercise prescription is sufficient to lose weight in the short term (12 wk) at a certain level. But exercise is more important for body composition, weight management and functional capacity. Long-term and in-depth studies should be conducted to interpret the results better.

Cervicothoracic ventral-dorsal rhizotomy for treatment of brachial hypertonia in cerebral palsy.

PURPOSE: Cervicothoracic ventral-dorsal rhizotomy (VDR) is a potential treatment of medically refractory hypertonia in patients who are not candidates for intrathecal baclofen, particularly in cases of severe upper limb hypertonia with limited to no function. A longitudinal cohort was identified to highlight our institutional safety and efficacy using cervicothoracic VDR for the treatment of hypertonia. METHODS: Retrospective data analysis was performed for patients that underwent non-selective cervicothoracic VDR between 2022 and 2023. Non-modifiable risk factors, clinical variables, and operative characteristics were collected. RESULTS: Six patients (three female) were included. Four patients underwent a bilateral C6-T1 VDR, one patient underwent a left C7-T1 VDR, and another underwent a left C6-T1 VDR. Three patients had quadriplegic mixed hypertonia, one patient had quadriplegic spasticity, one patient had triplegic mixed hypertonia, and one patient had mixed hemiplegic hypertonia. The mean difference of proximal upper extremity modified Ashworth scale (mAS) was - 1.4 ± 0.55 (p = 0.002), and - 2.2 ± 0.45 (p < 0.001) for the distal upper extremity. Both patients with independence noted quality of life improvements as well as increased ease with dressing and orthotics fits. Caregivers for the remaining four patients noted improvements in caregiving provision, mainly in dressing, orthotics fit, and ease when transferring. CONCLUSION: Cervicothoracic VDR is safe and provides tone control and quality of life improvements in short-term follow-up. It can be considered for the treatment of refractory hypertonia. Larger multicenter studies with longer follow-up are necessary to further determine safety along with long-term functional benefits in these patients.

Combined uranium-series and electron spin resonance dating from the Pliocene fossil sites of Aves and Milo's palaeocaves, Bolt's Farm, Cradle of Humankind, South Africa.

Bolt's Farm is the name given to a series of non-hominin bearing fossil sites that have often been suggested to be some of the oldest Pliocene sites in the Cradle of Humankind, South Africa. This article reports the results of the first combined Uranium-Series and Electron Spin Resonance (US-ESR) dating of bovid teeth at Milo's Cave and Aves Cave at Bolt's Farm. Both tooth enamel fragments and tooth enamel powder ages were presented for comparison. US-ESR, EU and LU models are calculated. Overall, the powder ages are consistent with previous uranium-lead and palaeomagnetic age estimates for the Aves Cave deposit, which suggest an age between ~3.15 and 2.61 Ma and provide the first ages for Milo's Cave dates to between ~3.1 and 2.7 Ma. The final ages were not overly dependent on the models used (US-ESR, LU or EU), which all overlap within error. These ages are all consistent with the biochronological age estimate (<3.4->2.6 Ma) based on the occurrence of Stage I Metridiochoerus andrewsi. Preliminary palaeomagnetic analysis from Milo's Cave indicates a reversal takes place at the site with predominantly intermediate directions, suggesting the deposit may date to the period between ~3.03 and 3.11 Ma within error of the ESR ages. This further suggests that there are no definitive examples of palaeocave deposits at Bolt's Farm older than 3.2 Ma. This research indicates that US-ESR dating has the potential to date fossil sites in the Cradle of Humankind to over 3 Ma. However, bulk sample analysis for US-ESR dating is recommended for sites over 3 Ma.

Comparison of oncological outcomes of upfront androgen receptor signaling inhibitors and combined androgen blockade in Japanese patients with metastatic castration-sensitive prostate cancer.

In recent years, randomized controlled trials have demonstrated that upfront androgen receptor signaling inhibitors (ARSIs) prolong overall survival (OS) compared with androgen deprivation therapy (ADT) alone or combined androgen blockade (CAB) in patients with metastatic castration-sensitive prostate cancer (mCSPC). However, it remains unclear whether upfront ARSI is superior to CAB in Asian populations, among which the efficacy of ADT/CAB is considered relatively high. In this study, we compared the oncological outcomes of upfront ARSI and CAB in Japanese patients with mCSPC. Patients with mCSPC who underwent systemic therapy between May 2009 and October 2023 were enrolled retrospectively. Propensity score matching (PSM) was performed to compare the castration-resistant prostate cancer-free survival (CRPC-FS), cancer-specific survival (CSS), and OS between patients treated with upfront ARSI (ARSI group) and those treated with CAB (CAB group). In total, 30 and 142 patients were enrolled in the ARSI and CAB groups, respectively. After PSM (25 patients in each group), CRPC-FS was significantly longer in the ARSI group than in the CAB group (median: 36.7 vs. 12.3 months, hazard ratio: 0.44, 95% confidence interval: 0.20-0.97, p = 0.035). No significant differences were observed in CSS or OS between the two groups. In conclusion, when compared to CAB, upfront ARSI might have the potential to extend CRPC-FS among individuals in the Japanese population.

Evaluating the impact of a combined aerobic and strength training intervention on the physical performance of male Chinese People's Liberation Army air force pilots.

This study aimed to assess the impact of a 16-week combined training program on the physical performance of 20 male Air Force pilots, with an average age of 31.87 ± 2.75 years, body mass of 76.33 ± 0.79 kg, and height of 175.55 ± 3.65 cm. This intervention encompassed both aerobic and strength training, involving six weekly training sessions. The participants were categorized into two groups based on their initial physical performance levels to explore potential baseline influences on post-intervention adaptations. The study measured changes in estimated maximal oxygen uptake (VO2 max), maximal strength, muscular endurance, and long jump performance before and after the training program. Repeated measures ANOVA revealed significant differences over time in the V ˙ O2 max (F = 86.898; p < 0.001; η p 2  = 0.821), handgrip strength right hand (F = 160.480; p < 0.001; η p 2  = 0.894), handgrip strength left hand (F = 102.196; p < 0.001; η p 2  = 0.843), squat maximal strength (F = 525.725; p < 0.001; η p 2  = 0.965), push-ups (F = 337.197; p < 0.001; η p 2  = 0.974), sit up (F = 252.500; p < 0.001; η p 2  = 0.930) and standing long jump (F = 521.714; p < 0.001; η p 2  = 0.965). In conclusion, the 16-week combined training regimen significantly enhanced the physical performance of Air Force pilots, regardless of their initial performance levels.

A Novel Combination Strategy of Ultrasound-Guided Percutaneous Radiofrequency Ablation and Corticosteroid Injection for Treating Recalcitrant Plantar Fasciitis: A Retrospective Comparison Study.

INTRODUCTION: The best treatment yielding clinical benefits was still equivocal and controversial for the treatment of recalcitrant plantar fasciitis (PF). This study aimed to propose a novel combination strategy of ultrasound-guided percutaneous radiofrequency ablation (RFA) and corticosteroid injection (CI) for recalcitrant PF, and to compare its therapeutic effects with CI alone and continued conservative management. METHODS: We retrospectively reviewed consecutive patients with recalcitrant PF who underwent combined strategy (RFA + CI), CI alone, and continue conservative treatment at our institution between October 2021 and February 2023. The technical pearls were described elaborately. A comparison of demographic data and clinical outcomes, including visual analog scale (VAS), Ankle-Hindfoot Scale (AOFAS-AHS), and plantar fascia thickness, were conducted among the three groups. RESULTS: Seventy-one eligible patients were enrolled in this study, with 17 in the combined strategy group, 25 in the CI group, and 29 in the continued conservative treatment group. Both the combined strategy group and the CI group showed significant improvements in VAS scores, AOFAS-AHS scores, and significant reductions in plantar fascia thickness during the 12-month follow-up period compared to those preoperatively (P < 0.05). The combined strategy group achieved comparable immediate pain relief to the CI group after the intervention ([25.7 ± 15.7] vs. [20.6 ± 17.6], P = 0.850). However, the combined strategy group demonstrated superior improvement in symptom and function compared to the CI group at the 3-month (VAS: [21.9 ± 13.5] vs. [39.6 ± 20.4]; AOFAS-AHS: [77.9 ± 12.4] vs. [60.5 ± 17.4], P < 0.05) and 12-month follow-up (VAS: [15.7 ± 12.0] vs. [56.8 ± 17.5]; AOFAS-AHS: [84.5 ± 10.7] vs. [53.8 ± 12.4], P < 0.05). Obvious adverse effects or complications were not identified in either group, while two cases (11.8%) in the combined strategy group and five cases (20.0%) in the CI group experienced unsatisfactory symptom remission. CONCLUSIONS: We introduced and detailed a novel combination strategy involving ultrasound-guided percutaneous RFA and CI for treating recalcitrant PF. The strategy is both effective and safe in alleviating pain and enhancing function throughout the entire treatment course.

A prediction model for stillbirth based on first trimester pre-eclampsia combined screening.

OBJECTIVE: To evaluate the accuracy of combined models of maternal biophysical factors, ultrasound, and biochemical markers for predicting stillbirths. METHODS: A retrospective cohort study of pregnant women undergoing first-trimester pre-eclampsia screening at 11-13 gestational weeks was conducted. Maternal characteristics and history, mean arterial pressure (MAP) measurement, uterine artery pulsatility index (UtA-PI) ultrasound, maternal ophthalmic peak ratio Doppler, and placental growth factor (PlGF) serum were collected during the visit. Stillbirth was classified as placental dysfunction-related when it occurred with pre-eclampsia or birth weight <10th percentile. Combined prediction models were developed from significant variables in stillbirths, placental dysfunction-related, and controls. We used the area under the receiver-operating-characteristics curve (AUC), sensitivity, and specificity based on a specific cutoff to evaluate the model's predictive performance by measuring the capacity to distinguish between stillbirths and live births. RESULTS: There were 13 (0.79%) cases of stillbirth in 1643 women included in the analysis. The combination of maternal factors, MAP, UtA-PI, and PlGF, significantly contributed to the prediction of stillbirth. This model was a good predictor for all (including controls) types of stillbirth (AUC 0.879, 95% CI: 0.799-0.959, sensitivity of 99.3%, specificity of 38.5%), and an excellent predictor for placental dysfunction-related stillbirth (AUC 0.984, 95% CI: 0.960-1.000, sensitivity of 98.5, specificity of 85.7). CONCLUSION: Screening at 11-13 weeks' gestation by combining maternal factors, MAP, UtA-PI, and PlGF, can predict a high proportion of stillbirths. Our model has good accuracy for predicting stillbirths, predominantly placental dysfunction-related stillbirths.

Expression levels and clinical significance of serum miR-19a/CCL20 in patients with acute cerebral infarction.

Acute cerebral infarction (ACI) is a lethal disease whose early diagnosis is critical for treatment. microRNA (miR)-19a targets CC chemokine ligand 20 (CCL20) in myocardial infarction. We investigated the expression patterns of serum miR-19a and CCL20 of ACI patients and assessed their clinical values. Serum samples of 50 healthy subjects and110 ACI patients were collected. Serum levels of miR-19a, CCL20 mRNA, and biochemical indexes were assessed. miR-19a downstream target gene and the binding relationship between miR-19a and CCL20 were predicted and verified. miR-19a and CCL20 mRNA were subjected to correlation and diagnostic efficiency analysis. miR-19a was poorly expressed in the serum of ACI patients, especially in patients with unstable plaque and large infarction. tumor necrosis factor-α, low-density lipoprotein, and platelet/lymphocyte ratio negatively correlated with serum miR-19a level and positively correlated with CCL20. Dual-luciferase assay revealed that miR-19a could negatively regulate CCL20 expression. CCL20 was highly expressed in the serum of ACI patients. The area under receiver-operating characteristic curve of miR-19a combined with CCL20 was 0.9741 (98.00% specificity, 90.91% sensitivity), higher than their single diagnosis. Collectively, miR-19a had high diagnostic value for ACI and could target to restrain CCL20. The combination of miR-19a and CCL20 improved diagnostic value for ACI.

Integrated analysis of single-cell RNA-seq, bulk RNA-seq, Mendelian randomization, and eQTL reveals T cell-related nomogram model and subtype classification in rheumatoid arthritis.

Objective: Rheumatoid arthritis (RA) is a systemic disease that attacks the joints and causes a heavy economic burden on humans worldwide. T cells regulate RA progression and are considered crucial targets for therapy. Therefore, we aimed to integrate multiple datasets to explore the mechanisms of RA. Moreover, we established a T cell-related diagnostic model to provide a new method for RA immunotherapy. Methods: scRNA-seq and bulk-seq datasets for RA were obtained from the Gene Expression Omnibus (GEO) database. Various methods were used to analyze and characterize the T cell heterogeneity of RA. Using Mendelian randomization (MR) and expression quantitative trait loci (eQTL), we screened for potential pathogenic T cell marker genes in RA. Subsequently, we selected an optimal machine learning approach by comparing the nine types of machine learning in predicting RA to identify T cell-related diagnostic features to construct a nomogram model. Patients with RA were divided into different T cell-related clusters using the consensus clustering method. Finally, we performed immune cell infiltration and clinical correlation analyses of T cell-related diagnostic features. Results: By analyzing the scRNA-seq dataset, we obtained 10,211 cells that were annotated into 7 different subtypes based on specific marker genes. By integrating the eQTL from blood and RA GWAS, combined with XGB machine learning, we identified a total of 8 T cell-related diagnostic features (MIER1, PPP1CB, ICOS, GADD45A, CD3D, SLFN5, PIP4K2A, and IL6ST). Consensus clustering analysis showed that RA could be classified into two different T-cell patterns (Cluster 1 and Cluster 2), with Cluster 2 having a higher T-cell score than Cluster 1. The two clusters involved different pathways and had different immune cell infiltration states. There was no difference in age or sex between the two different T cell patterns. In addition, ICOS and IL6ST were negatively correlated with age in RA patients. Conclusion: Our findings elucidate the heterogeneity of T cells in RA and the communication role of these cells in an RA immune microenvironment. The construction of T cell-related diagnostic models provides a resource for guiding RA immunotherapeutic strategies.

Combined Anterolateral and Posterior Approach in Total Hip Arthroplasty for Chronic Post-traumatic Hip Dislocation: A Case Report.

Hip dislocation is rare, and it typically results from high-energy trauma such as traffic accidents. Its management involves prompt reduction of the dislocated hip to minimize the risk of subsequent femoral head necrosis. Consequently, cases of chronic hip dislocation are extremely rare. This report presents a case of a 33-year-old male with chronic posterior hip dislocation due to a traffic accident 13 years ago. The left femoral head was completely dislocated posteriorly from the acetabulum, forming a false acetabulum with an arthritic change. The patient experienced difficulty walking and performing daily activities due to pain. We performed a total hip arthroplasty (THA) using a combined anterolateral and posterior approach. The outcome was favorable, with no complications during the two-year follow-up period. THA using a combined anterolateral and posterior approach is a valuable option for patients with chronic post-traumatic hip dislocation because it offers the advantages of optical visibility and the management of the adhered soft tissues.

Multimodal therapeutic intervention program associated with photobiomodulation therapy for individuals with chronic nonspecific neck pain: protocol for a clinical trial.

BACKGROUND: Neck pain is a prevalent global musculoskeletal issue, significantly contributing to the loss of years of healthy life due to disability. Chronic nonspecific neck pain (CNNP) involves diverse symptoms impacting mobility and quality of life. While therapeutic exercises demonstrate efficacy, the role of photobiomodulation therapy (PBMT) remains uncertain. This study aims to assess the additional effects of PBMT within a multimodal therapeutic intervention for CNNP. METHODS: A randomized, two-arm, controlled, blind clinical trial follows CONSORT and SPIRIT guidelines. Participants diagnosed with CNNP will receive a stand-alone multimodal therapeutic intervention or the same program with additional PBMT. The primary outcomes will be assessed by the functional disability identified through applying the NDI (Neck Disability Index). Secondary outcomes will be pain intensity during rest and active neck movement, catastrophizing and kinesiophobia, functionality, and disability assessed at baseline, after 8 weeks, and at a 4-week follow-up. Both groups receive pain education before personalized interventions, including resistance exercises, neuromuscular activities, mobility, and body balance. The PBMT group undergoes low-level light therapy. Intention-to-treat analysis, using linear mixed models, employs data presented as mean, standard deviation, and differences with a 95% confidence interval. Non-normally distributed variables transform. Statistical significance is set at 5%. DISCUSSION: This study addresses a critical gap in understanding the combined effects of PBMT and therapeutic exercises for CNNP. The findings aim to guide clinicians, researchers, and CNNP sufferers through rigorous methodology and diverse outcome assessments, offering valuable insights into evidence-based practices for CNNP management. Data confidentiality is maintained throughout, ensuring participant privacy during statistical analysis. TRIAL REGISTRATION: Effects of adding photobiomodulation to a specific therapeutic exercise program for the treatment of individuals with chronic nonspecific neck pain, registration number: NCT05400473, on 2022-05-27.

Endoscopic combined intrarenal surgery without ureteral access sheath performed for renal stone after Cohen reimplantation.

Introduction: Endoscopic combined intrarenal surgery after anti-reflux operation is rarely performed. Case presentation: A 37-year-old female was referred to our hospital for treatment of left renal stone. She underwent anti-reflux surgery (Cohen reimplantation) for left vesicoureteral reflux at the age of 10 years. Computed tomography revealed a 17 × 11 mm left inferior calyceal calculus. The patient received retrograde double-J stent insertion under radiographic guidance and underwent ultra-mini endoscopic combined intrarenal surgery without ureteral access sheath. The patient was discharged on postoperative Day 5 with no postoperative complications. Postoperative cystography showed no recurrence of vesicoureteral reflux. One month after the operation, kidney-ureter-bladder radiography and computed tomography scan revealed no residual stones or hydronephrosis. Conclusion: Ultra-mini endoscopic combined intrarenal surgery without ureteral access sheath is an effective method for treating renal stones after Cohen reimplantation.

The impact of co-exposure to polystyrene microplastics and norethindrone on gill histology, antioxidant capacity, reproductive system, and gut microbiota in zebrafish (Danio rerio).

In recent years, studies have focused on the combined ecological risks posed by microplastics and other organic pollutants. Although both microplastics and progestin residues are frequently detected in the aquatic environments, their ecological implications remain unknown. Adult zebrafish were exposed to polystyrene microplastics (PS, 200 nm, 200 µg/L), norethindrone (NET, 69.6 ng/L), and their mixture (200 µg/L PS + 63.1 ng/L NET) for 30 days. The results demonstrated that exposure to PS and NET resulted in gill damage. Notably, the PS and PS+NET exhibited a significant decrease in glutathione (GSH) and oxidized glutathione (GSSG) content, as well as reduced antioxidase activity in the gills. The oxidative stress in PS+NET primarily originated from PS. The PS, NET, or their mixture resulted in a decrease in testosterone (T) and estradiol (E2) levels in female. Furthermore, compared to NET, the PS+NET showed a significant reduction in E2 levels, thereby augmenting the inhibitory effect on reproductive ability mediated by NET. However, males showed an increase in 11-ketodihydrotestosterone (11-KT) content, accompanied by a significant decrease in spermatogonia (Sg) and increase in spermatocytes (Sc). Consequently, it can be inferred that PS enhances the androgenic effect of NET. In female fish brain, NET alone resulted in transcriptional down-regulation of partial hormone receptors; however, co-administration of PS effectively mitigated the interference effects. Furthermore, transcriptional downregulation of 17-alpha-hydroxylase (cyp17), hydroxysteroid 3-beta dehydrogenase (hsd3b), estrogen receptor 1 (esr1), and estrogen receptor 2a (esr2b) genes in the ovary was found to be associated with the androgenic activity induced by NET. Moreover, in comparison to PS or NET alone, PS+NET resulted in a notable decrease in Cetobacterium abundance and an increase in Aeromonas population, suggesting that the co-exposure of PS+NET may exacerbate intestinal burden. The findings highlight the importance of studying the combined toxicity of PS and NET.

A Fe2O3/CNx cascade nanoreactor with dual-enzyme-mimetic activities for cancer hypoxia relief to amplify chemo/photodynamic therapy.

Reactive oxygen species (ROS)-mediated therapeutic strategies, including chemodynamic therapy (CDT), photodynamic therapy (PDT), and their combination, are effective for treating cancer. Developing a nanoreactor with combined functions of catalase (CAT) and peroxidase (POD) that can simultaneously convert excess H2O2 in tumors into O2 required for type II PDT and hydroxyl radicals (•OH) for CDT can help achieve combined therapy. Here, we reported on a safe Fe2O3/CNx nanoreactor with dual enzyme simulated activity, in which CNx sheet was the carrier and reducing agent to convert Fe2O3 to Fe2+. After modified by MgO2 and photosensitizer Ce6, MgO2-Fe2O3/CNx-Ce6 (MFCC) platform integrated multiple functions, including photosensitizer delivery, compensated H2O2 continuous supply, relieve of hypoxia, generation of •OH and consumption of GSH into a single formulation. Under 660 nm irradiation for 4 min, MFCC actives more ROS to conduct PDT/CDT, leading to the remarkable reduced survival rate of breast cancer cells to 14 %. Due to the enhanced permeability and retention (EPR) effect, MFCC can retain and accumulate at the tumor site of mice for a longer period that inhibit the expression of tumor angiogenic factors, suppress tumor neovascularization, and suppress the proliferation and growth of tumor cells.

The effect of combined head and tail approach during laparoscopic D3 lymph node dissection on pain severity and complications in patients with right colon cancer.

OBJECTIVE: To examine the impact of a combined craniocaudal approach on pain and complications during laparoscopic D3 lymph node dissection in clients diagnosed with right colon cancer (RCC). METHODS: 100 RCC patients were divided into Group A and Group B. Both groups underwent laparoscopic D3 lymph node dissection, with Group A undergoing an intermediate approach and Group B undergoing a combined head and tail approach. Two groups of patients' perioperative (surgical time, intraoperative blood loss, number of lymph node dissection) indicators, postoperative recovery (postoperative exhaust time, postoperative hospital stay, drainage tube removal time) indicators, perioperative pain level (VAS scores 1, 3, and 5 days following surgery), and incidence of complications (vascular injury, intestinal obstruction, anastomotic bleeding, incision infection), and the therapeutic efficacy [CEA, CA19-9] indicators were compared. RESULTS: Clients in the B team had substantially shorter operating times and considerably fewer intraoperative hemorrhage than those in the A team. The VAS grades of clients in the B team were considerably lower than those in the A team the day following surgery. Clients in the B team experienced vascular injury at a substantially lower rate than those in the A team. The overall incidence rate of problems did not differ statistically significantly between the A team and the B team. Following therapy, teams A and B's CEA and CA19-9 levels were considerably lower than those of the same team prior to therapy. CONCLUSION: Combined craniocaudal technique can significantly reduce intraoperative bleeding, postoperative pain, and the risk of sequelae from vascular injuries.

Combined effects of microplastics and pharmaceutical and personal care products on algae: A critical review.

Microplastics (MPs) and pharmaceuticals and personal care products (PPCPs) are ubiquitous in aquatic environments. Algae play an important role in aquatic environments. Thus, it is important to study the response of algae to combined exposure of MPs and PPCPs. Here, we review the effects of MPs and PPCPs on algae. First, the individual effects of MPs and PPCPs on algae were summarized. Second, the combined effects of MPs and PPCPs on algae were systematically analyzed. (1) Antagonism: ① when the MPs are too large to enter the algal cells, the adsorption of PPCPs onto MPs results in decreased the contact of MPs and PPCPs with algae; ② PPCPs and MPs have opposing actions on the same biological target; ③ MPs increase the activity of metabolic enzymes in algae, thus promoting the PPCP degradation. (2) Synergy: ① when the MPs are small enough to enter algal cells, the adsorption of PPCPs on MPs promotes the entry of PPCPs; ② when MPs are negatively charged, the adsorption of positively charged PPCPs by MPs decreases the electrostatic repulsion, increasing the interaction between algae and MPs; ③ complementary modes of action between MPs and PPCPs show combined effects on the same biological target. Third, the relative importance of the factors that impact the combined effects are evaluated using the random forest model decreased in the following order: PPCP types > algal species > MP size > MP concentration > MP types > exposure time. Finally, future directions for the combined effects of MPs and PPCPs are proposed, which will facilitate a better understanding of the environmental fate and risks of both MPs and PPCPs.

Combining cashew gum with cyclophosphamide in murine melanoma model: A strategy for the reduction of side effects.

The understanding of cancer immunity and antitumor factors generated by natural polysaccharides is not yet fully comprehended. Polysaccharides, like cashew gum (CG), can exhibit immunomodulatory action and may assist in the antitumor process and side effects relieve. This study aimed to determine the antitumor effect of CG alone or in combination with cyclophosphamide (CTX), and its interactions with immune cells, in a murine melanoma model, using the B16-F10 cell line. Tumor growth inhibition, hematological, histopathological, ELISA, flow cytometry, immunofluorescence, and qRT-PCR analyses were performed to elucidate the antitumor potential, involvement of immune cells, and potential toxic effects. CG showed significant tumor growth inhibition, reaching up to 42.9 % alone and 51.4 % in combination with CTX, with mild toxicity to organs. CG enhanced leukocyte count, even in the presence of CTX. Furthermore, CG influenced the activation of tumor-associated macrophages (TAM), characterized by an increase in Il4, as well as a reduction in Ifng, Il1b, Tgfb, and Il6 gene expression. Nevertheless, these effects did not compromise the antitumor activity of CG. In summary, the combination of CG with CTX is a promising approach for leukopenia, one of the most important side effects of cancer treatment and deserves further investigation.

A synthetic bacterial consortium improved the phytoremediation efficiency of ryegrass on polymetallic contaminated soil.

Polymetallic contamination of soils caused by mining activities seriously threatens soil fertility, biodiversity and human health. Bioremediation is thought to be of low cost and has minimal environmental risk but its effectiveness needs to be improved. This study aimed to identify the combined effect of plant growth and microbial strains with different functions on the enhancement of bioremediation of polymetallic contaminated soil. The microbiological mechanism of bioremediation was explored by amplicon sequencing and gene prediction. Soil was collected from polymetallic mine wastelands and a non-contaminated site for use in a pot experiment. Remediation efficiency of this method was evaluated by planting ryegrass and applying a mixed bacterial consortium comprising P-solubilizing, N-fixing and SO4-reducing bacteria. The plant-microbe joint remediation method significantly enhanced the above-ground biomass of ryegrass and soil nutrient contents, and at the same time reduced the content of heavy metals in the plant shoots and soil. The application of the composite bacterial inoculum significantly affected the structure of soil bacterial communities and increased the bacterial diversity and complexity, and the stability of co-occurrence networks. The relative abundance of the multifunctional genera to which the strains belonged showed a significant positive correlation with the soil nutrient content. Genera related to carbon (C), nitrogen (N), phosphorus (P), and sulphur (S) cycling and heavy metal resistance showed an up-regulation trend in heavy metal-contaminated soils after the application of the mixed bacterial consortium. Also, bacterial strains with specific functions in the mixed consortium regulated the expression of genes involved in soil nutrient cycling, and thus assisted in making the soil self-sustainable after remediation. These results suggested that the remediation of heavy metal-contaminated soil needs to give priority to the use of multifunctional bacterial agents.