Unveiling Advancements: Trends and Hotspots of Metal-Organic Frameworks in Photocatalytic CO2 Reduction.

Metal-organic frameworks (MOFs) are robust, crystalline, and porous materials featured by their superior CO2 adsorption capacity, tunable energy band structure, and enhanced photovoltaic conversion efficiency, making them highly promising for photocatalytic CO2 reduction reaction (PCO2RR). This study presents a comprehensive examination of the advancements in MOFs-based PCO2RR field spanning the period from 2011 to 2023. Employing bibliometric analysis, the paper scrutinizes the widely adopted terminology and citation patterns, elucidating trends in publication, leading research entities, and the thematic evolution within the field. The findings highlight a period of rapid expansion and increasing interdisciplinary integration, with extensive international and institutional collaboration. A notable emphasis on significant research clusters and key terminologies identified through co-occurrence network analysis, highlighting predominant research on MOFs such as UiO, MIL, ZIF, porphyrin-based MOFs, their composites, and the hybridization with photosensitizers and molecular catalysts. Furthermore, prospective design approaches for catalysts are explored, encompassing single-atom catalysts (SACs), interfacial interaction enhancement, novel MOF constructions, biocatalysis, etc. It also delves into potential avenues for scaling these materials from the laboratory to industrial applications, underlining the primary technical challenges that need to be overcome to facilitate the broader application and development of MOFs-based PCO2RR technologies.

Unicondylar knee arthroplasty demonstrating a significant increased risk for aseptic revisions compared to unconstrained and constrained total knee arthroplasty: An analysis of aseptic revisions after unicondylar and primary total knee arthroplasty of the German Arthroplasty Registry.

PURPOSE: Due to ageing population, the implantation rate of total knee arthroplasties (TKAs) is continuously growing. Aseptic revisions in primary knee arthroplasty are a major cause of revision. The aim of the following study was to determinate the incidence and reasons of aseptic revisions in constrained and unconstrained TKA, as well as in unicondylar knee arthroplasties (UKAs). METHODS: Data collection was performed using the German Arthroplasty Registry. Reasons for aseptic revisions were calculated. Incidence and comparison of aseptic revisions were analysed using Kaplan-Meier estimates. A multiple χ2 test with Holm's method was used to detect group differences in ligament ruptures. RESULTS: Overall, 300,998 cases of knee arthroplasty with 254,144 (84.4%) unconstrained TKA, 9993 (3.3%) constrained TKA and 36,861 (12.3%) UKA were analysed. Aseptic revision rate in UKA was significantly increased compared to unconstrained and constrained TKA (p < 0.0001). In constrained TKA, a 2.0% revision rate for aseptic reasons were reported after 1 year, while in unconstrained TKA 1.1% and in UKA, 2.7% of revisions were identified. After 7 years in constrained TKA 3.3%, in unconstrained TKA 2.8%, and in UKA 7.8% sustained aseptic revision. Ligament instability was the leading cause of aseptic revision accounting for 13.7% in unconstrained TKA. In constrained TKA, 2.8% resulted in a revision due to ligament instability. In the UKA, the most frequent cause of revisions was tibial loosening, accounting for 14.6% of cases, while progression of osteoarthritis accounted for 7.9% of revisions. Ligament instability was observed in 14.1% of males compared to 15.9% of females in unconstrained TKA and in 4.6% in both genders in UKA. CONCLUSION: In patients with UKA, aseptic revision rates are significantly higher compared to unconstrained and constrained TKA. Ligament instability was the leading cause of aseptic revision in unconstrained TKA. In UKA, the most frequent cause of revisions was tibial loosening, while progression of osteoarthritis was the second most frequent cause of revisions. Comparable levels of ligament instability were observed in both sexes. LEVEL OF EVIDENCE: Level III, cohort study.

Low implantation volume, comorbidities, male sex and implantation of constrained TKA identified as risk factors for septic revision in knee arthroplasty: A register-based study from the German Arthroplasty Registry.

PURPOSE: Periprosthetic joint infection (PJI) is a major cause of revision surgery after total knee arthroplasty (TKA) and unicondylar knee arthroplasty (UKA). Patient- and hospital-related risk factors need to be assessed to prevent PJI. This study identifies influential factors and differences in infection rates between different implant types. METHODS: Data were obtained from the German Arthroplasty Registry. Septic revisions were calculated using Kaplan-Meier estimates with septic revision surgery as the primary endpoint. Patients with constrained and unconstrained TKA or UKA were analysed using Holm's multiple log-rank test and Cox's proportional hazards ratio. The 300,998 cases of knee arthroplasty analysed included 254,144 (84.4%) unconstrained TKA, 9993 (3.3%) constrained TKA and 36,861 (12.3%) UKA with a maximum follow-up of 7 years. RESULTS: At 1 year, the PJI rate was 0.5% for UKA and 2.8% for TKA, whereas at 7 years, the PJI rate was 4.5% for UKA and 0.9% for TKA (p < 0.0001). The PJI rate significantly increased for constrained TKA compared to unconstrained TKA (p < 0.0001). The PJI rate was 2.0% for constrained TKA and 0.8% for unconstrained TKA at 1 year and 3.1% and 1.4% at 7 years. Implantation of a constrained TKA (hazard ratio [HR] = 2.55), male sex (HR = 1.84), increased Elixhauser score (HR = 1.18-1.56) and implant volume of less than 25 UKA per year (HR = 2.15) were identified as risk factors for revision surgery; an Elixhauser score of 0 (HR = 0.80) was found to be a preventive factor. CONCLUSIONS: Reduced implant volume and constrained knee arthroplasty are associated with a higher risk of PJI. Comorbidities (elevated Elixhauser score), male sex and low UKA implant volume have been identified as risk factors for PJI. Patients who meet these criteria require specific measures to prevent infection. Further research is required on the potential impact of prevention and risk factor modification. LEVEL OF EVIDENCE: Level III.

Biological Renewable Cellulose-Templated Zn1-XCuXO/Ag2O Nanocomposite Photocatalysts for the Degradation of Methylene Blue.

Herein, Cellulose-templated Zn1-XCuXO/Ag2O nanocomposites were prepared using biological renewable cellulose extracted from water hyacinth (Eichhornia crassipes). Cellulose-templated Cu-doped ZnO catalysts with different amounts of Cu as the dopants (1, 2, 3, and 4%) were prepared and denoted CZ-1, CZ-2, CZ-3, and CZ-4, respectively, for simplicity. The prepared catalysts were tested for the degradation of methylene blue (MB), and 2% Cu-doped ZnO (CZ-2) showed the best catalytic performance (82%), while the pure ZnO, CZ-1, CZ-3, and CZ-4 catalysts exhibited MB dye degradation efficiencies of 54, 63, 65, and 60%, respectively. The best catalyst (CZ-2) was chosen to further improve the degradation efficiency. Different amounts of AgNO3 (10, 15, 30, and 45 mg) were used for the deposition of Ag2O on the surface of CZ-2 and denoted CZA-10, CZA-15, CZA-30, and CZA-45, respectively. Among the composite catalysts, CZA-15 showed remarkable degradation efficiency and degraded 94% of MB, while the CZA-10, CZA-30, and CZA-45 catalysts showed 90, 81, and 79% degradation efficiencies, respectively, under visible light within 100 min of irradiation. The enhanced catalytic performance could be due to the smaller particle size, the higher electron and hole separation and charge transfer efficiencies, and the lower agglomeration in the composite catalyst system. The results also demonstrated that the Cu-doped ZnO prepared with cellulose as a template, followed by the optimum amount of Ag2O deposition, could have promising applications in the degradation of organic pollutants.

UiO-66(Zr) as drug delivery system for non-steroidal anti-inflammatory drugs.

The toxicity for the human body of non-steroidal anti-inflammatory drugs (NSAIDs) overdoses is a consequence of their low water solubility, high doses, and facile accessibility to the population. New drug delivery systems (DDS) are necessary to overcome the bioavailability and toxicity related to NSAIDs. In this context, UiO-66(Zr) metal-organic framework (MOF) shows high porosity, stability, and load capacity, thus being a promising DDS. However, the adsorption and release capability for different NSAIDs is scarcely described. In this work, the biocompatible UiO-66(Zr) MOF was used to study the adsorption and release conditions of ibuprofen, naproxen, and diclofenac using a theoretical and experimental approximation. DFT results showed that the MOF-drug interaction was due to an intermolecular hydrogen bond between protons of the groups in the defect sites, (µ3 - OH, and - OH2) and a lone pair of oxygen carboxyl functional group of the NSAIDs. Also, the experimental results suggest that the solvent where the drug is dissolved affects the adsorption process. The adsorption kinetics are similar between the drugs, but the maximum load capacity differs for each drug. The release kinetics assay showed a solvent dependence kinetics whose maximum liberation capacity is affected by the interaction between the drug and the material. Finally, the biological assays show that none of the systems studied are cytotoxic for HMVEC. Additionally, the wound healing assay suggests that the UiO-66(Zr) material has potential application on the wound healing process. However, further studies should be done.

Hierarchical Porous Bimetallic FeMn Metal-Organic Framework Gel for Efficient Activation of Peracetic Acid in Antibiotic Degradation.

Effective techniques for eliminating antibiotics from water environments are in high demand. The peracetic acid (PAA)-based advanced oxidation process has recently drawn increasing attention for its effective antibiotic degrading capability. However, current applications of PAA-based techniques are limited and tend to have unsatisfactory performance. An additional catalyst for PAA activation could provide a promising solution to improve the performance of PAA. Bulky metal-organic framework gels (MOGs) stand out as ideal catalysts for PAA activation owing to their multiple advantages, including large surface areas, high porosity, and hierarchical pore systems. Herein, a bimetallic hierarchical porous structure, i.e., FeMn13BTC, was synthesized through a facile one-pot synthesis method and employed for PAA activation in ofloxacin (OFX) degradation. The optimized FeMn MOG/PAA system exhibited efficient catalytic performance, characterized by 81.85% OFX degradation achieved within 1 h owing to the specific hierarchical structure and synergistic effect between Fe and Mn ions, which greatly exceeded the performance of the only PAA-catalyzed system. Furthermore, the FeMn MOG/PAA system maintained >80% OFX degradation in natural water. Quenching experiments, electron spin resonance spectra, and model molecular degradation revealed that the primary reactive oxygen species responsible for the catalytic effect was R-O•, especially CH3C(=O)OO•, with minor contributions of •OH and 1O2. Overall, introduction of the MOG catalyst strategy for PAA activation achieved high antibiotic degradation performance, establishing a paradigm for the design of heterogeneous hierarchical systems to broaden the scope of catalyzed water treatment applications.

Gamma irradiation induced degradation of organic pollutants: Recent advances and future perspective.

Different organic compounds in aquatic bodies have been recognized as an emerging issue in Environmental Chemistry. The gamma irradiation technique, as one of the advanced oxidation techniques, has been widely investigated in past decades as a technique for the degradation of organic molecules, such as dyes, pesticides, and pharmaceuticals, which show high persistence to degradation. This review gives an overview of what has been achieved so far using gamma irradiation for different organic compound degradations giving an explanation of the mechanisms of degradations as well as the corresponding limitations and drawbacks, and the answer to why this technique has not yet widely come to life. Also, a new approach, recently presented in the literature, regards coupling gamma irradiation with other techniques and materials, as the latest trend. A critical evaluation of the most recent advances achieved by coupling gamma irradiation with other methods and/or materials, as well as describing the reaction mechanisms of coupling, that is, additional destabilization of molecules achieved by coupling, emphasizing the advantages of the newly proposed approach. Finally, it was concluded what are the perspectives and future directions towards its commercialization since this technique can contribute to waste minimization i.e. not waste transfer to other media. Summarizing and generalization the model of radiolytic degradation with and without coupling with other techniques can further guide designing a new modular, mobile method that will satisfy all the needs for its wide commercial application.

Short-course neoadjuvant radiotherapy combined with chemotherapy and toripalimab for locally advanced esophageal squamous cell carcinoma (SCALE-1): a single-arm phase Ib clinical trial.

BACKGROUND: The optimal dosages, timing, and treatment sequencing for standard-of-care neoadjuvant chemoradiotherapy necessitate re-evaluation when used in conjunction with immune checkpoint inhibitors for patients with resectable, locally advanced esophageal squamous cell carcinoma (RLaESCC). The SCALE-1 phase Ib study aimed to evaluate the safety and efficacy of short-course neoadjuvant radiotherapy combined with chemotherapy and toripalimab in this patient population. METHODS: RLaESCC patients with clinical stages cT3-4aN0M0/cT1-4aN+M0 received neoadjuvant paclitaxel (135 mg/m2), carboplatin (area under the curve=5), and toripalimab (240 mg) every 3 weeks for two cycles. Short-course neoadjuvant radiotherapy (30 Gy in 12 fractions; 5 days per week) was administered between neoadjuvant immune-chemotherapy (nICT) doses. Esophagectomies were scheduled 4-6 weeks after completing neoadjuvant treatment. The primary endpoint was safety, with secondary endpoints including pathological complete response (pCR) rate, postoperative complications, progression-free survival (PFS), and overall survival (OS). Exploratory biomarker analysis used gene expression profiles via the nCounter platform. RESULTS: Of the 23 patients enrolled, all completed neoadjuvant radiotherapy, while 21 cases finished full nICT doses and cycles. Common grade 3/4 adverse events included neutropenia (57%), leukopenia (39%), and skin rash (30%). No grade 3 or higher esophagitis or pneumonitis occured. Twenty patients underwent surgery, and 11 achieved pCR (55%). Two patients (10%) experienced grade IIIb surgical complications. At the database lock, a 2-year PFS rate of 63.8% (95% CI 43.4% to 84.2%) and 2-year OS rate was 78% (95% CI 64.9% to 91.1%) were achieved. Tumor immune microenvironment analysis indicated that tumors with pCR exhibited significantly higher pretreatment T-cell-inflamed score and post-treatment reshaping of antitumor immunity. CONCLUSIONS: Combining short-course neoadjuvant radiotherapy with chemotherapy and toripalimab demonstrated favorable safety and promising efficacy in RLaESCC patients. TRIAL REGISTRATION NUMBER: ChiCTR2100045104.

Photocatalytic activity of the biogenic mediated green synthesized CuO nanoparticles confined into MgAl LDH matrix.

The global concern over water pollution caused by organic pollutants such as methylene blue (MB) and other dyes has reached a critical level. Herein, the Allium cepa L. peel extract was utilized to fabricate copper oxide (CuO) nanoparticles. The CuO was combined with MgAl-layered double hydroxides (MgAl-LDHs) via a co-precipitation method with varying weight ratios of the CuO/LDHs. The composite catalysts were characterized and tested for the degradation of MB dye. The CuO/MgAl-LDH (1:2) showed the highest photocatalytic performance and achieved 99.20% MB degradation. However, only 90.03, 85.30, 71.87, and 35.53% MB dye was degraded with CuO/MgAl-LDHs (1:1), CuO/MgAl-LDHs (2:1), CuO, and MgAl-LDHs catalysts, respectively. Furthermore, a pseudo-first-order rate constant of the CuO/MgAl-LDHs (1:2) was 0.03141 min-1 while the rate constants for CuO and MgAl-LDHs were 0.0156 and 0.0052 min-1, respectively. The results demonstrated that the composite catalysts exhibited an improved catalytic performance than the pristine CuO and MgAl-LDHs. The higher photocatalytic performances of composite catalysts may be due to the uniform distribution of CuO nanoparticles into the LDH matrix, the higher surface area, and the lower electron and hole recombination rates. Therefore, the CuO/MgAl-LDHs composite catalyst can be one of the candidates used in environmental remediation.

National survey on the availability of oncology palliative care services at tertiary general and cancer hospitals in China.

BACKGROUND: This nationwide survey studied the level of palliative care (PC) access for Chinese patients with cancer among cancer care providers either in tertiary general hospitals or cancer hospitals in China. METHODS: Using a probability-proportionate-to-size method, we identified local tertiary general hospitals with oncology departments to match cancer hospitals at the same geographic area. A PC program leader or a designee at each hospital reported available PC services, including staffing, inpatient and outpatient services, education, and research, with most questions adapted from a previous national survey on PC. The primary outcome was availability of a PC service. RESULTS: Most responders reported that some type of PC service (possibly called "comprehensive cancer care," "pain and symptom management," or "supportive care") was available at their institution (84.3% of tertiary general hospitals, 82.8% of cancer hospitals). However, cancer hospitals were significantly more likely than tertiary general hospitals to have a PC department or specialist (34.1% vs. 15.5%, p < 0.001). The most popular services were pain consultation (> 92%), symptom management (> 77%), comprehensive care plans (~ 60%), obtaining advanced directives and do-not-resuscitate orders (~ 45%), referrals to hospice (> 32%), and psychiatric assessment (> 25%). Cancer hospitals were also more likely than tertiary general hospitals to report having inpatient beds for PC (46.3% vs. 30.5%; p = 0.010), outpatient PC clinics (28.0% vs. 16.8%; p = 0.029), educational programs (18.2% vs. 9.0%, p = 0.014), and research programs (17.2% vs. 9.3%, p < 0.001). CONCLUSIONS: Cancer hospitals are more likely to offer PC than are tertiary general hospitals in China. Our findings highlight opportunities to further increase the PC capacity in Chinese hospitals.

The use of antibiotic-loaded bone cement and systemic antibiotic prophylactic use in 2,971,357 primary total knee arthroplasties from 2010 to 2020: an international register-based observational study among countries in Africa, Europe, North America, and Oceania.

BACKGROUND AND PURPOSE: Antibiotic-loaded bone cement (ALBC) and systemic antibiotic prophylaxis (SAP) have been used to reduce periprosthetic joint infection (PJI) rates. We investigated the use of ALBC and SAP in primary total knee arthroplasty (TKA). PATIENTS AND METHODS: This observational study is based on 2,971,357 primary TKAs reported in 2010-2020 to national/regional joint arthroplasty registries in Australia, Denmark, Finland, Germany, Italy, the Netherlands, New Zealand, Norway, Romania, South Africa, Sweden, Switzerland, the UK, and the USA. Aggregate-level data on trends and types of bone cement, antibiotic agents, and doses and duration of SAP used was extracted from participating registries. RESULTS: ALBC was used in 77% of the TKAs with variation ranging from 100% in Norway to 31% in the USA. Palacos R+G was the most common (62%) ALBC type used. The primary antibiotic used in ALBC was gentamicin (94%). Use of ALBC in combination with SAP was common practice (77%). Cefazolin was the most common (32%) SAP agent. The doses and duration of SAP used varied from one single preoperative dosage as standard practice in Bolzano, Italy (98%) to 1-day 4 doses in Norway (83% of the 40,709 TKAs reported to the Norwegian arthroplasty register). CONCLUSION: The proportion of ALBC usage in primary TKA varies internationally, with gentamicin being the most common antibiotic. ALBC in combination with SAP was common practice, with cefazolin the most common SAP agent. The type of ALBC and type, dose, and duration of SAP varied among participating countries.

Discovering Dynamic Plant Enzyme Complexes in Yeast for Kratom Alkaloid Pathway Identification.

Discovering natural product biosynthetic pathways of medicinal plants is challenging and laborious. Capturing the coregulation patterns of pathway enzymes, particularly transcriptomic regulation, has proven an effective method to accelerate pathway identification. In this study, we developed a yeast-based screening method to capture the protein-protein interactions (PPI) between plant enzymes, which is another useful pattern to complement the prevalent approach. Combining this method with plant multiomics analysis, we discovered four enzyme complexes and their organized pathways from kratom, an alkaloid-producing plant. The four pathway branches involved six enzymes, including a strictosidine synthase, a strictosidine ß-D-glucosidase (MsSGD), and four medium-chain dehydrogenase/reductases (MsMDRs). PPI screening selected six MsMDRs interacting with MsSGD from 20 candidates predicted by multiomics analysis. Four of the six MsMDRs were then characterized as functional, indicating the high selectivity of the PPI screening method. This study highlights the opportunity of leveraging post-translational regulation features to discover novel plant natural product biosynthetic pathways.

Recent progress on plant extract-mediated biosynthesis of ZnO-based nanocatalysts for environmental remediation: Challenges and future outlooks.

The plant extract mediated green synthesis of nanomaterials has attracts enormous interest due to its cost-effectiveness, greener, and environmentally friendly. It is also considered as an alternative and facile method in which the phytochemicals can be used as a natural capping and reducing agents and helped to produce nanomaterials with high surface area, different sizes, and shapes. One of the materials fabricated using green methods is zinc oxide (ZnO) semiconductor due to its enormous applications in different field areas. In this review, an overview of recent progress on green synthesized ZnO-based catalysts and various modification methods for the purpose of enhancing the catalytic activity of ZnO and the corresponding structural-activity and interactions towards the removal of pollutants are highlighted. Particularly, the plant extract mediated ZnO-based photocatalysts application for the removal of pollutants via photocatalytic degradation, reduction reaction, and adsorption mechanism are demonstrated. Besides, the opportunities, challenges, and future outlooks of ZnO-based materials for environmental remediation with green and sustainable methods are also included. We believe that this review is a timely and comprehensive review on the recent progress related to plant extract mediated ZnO-based nanocatalysts synthesis and applications for environmental remediation.

Improved stability and activity of laccase through de novo and post-synthesis immobilization on a hierarchically porous metal-organic framework (ZIF-8).

Porous materials such as metal-organic frameworks (MOFs) are considered to be suitable materials for immobilizing enzymes to improve their stability. However, conventional MOFs reduce the enzymes' catalytic activity due to difficulties with mass transfer and diffusing reactants after their micropores are occupied by enzyme molecules. To address these issues, a novel hierarchically structured zeolitic imidazolate framework-8 (HZIF-8) was prepared to study the effects of different laccase immobilization approaches such as the post-synthesis (LAC@HZIF-8-P) and de novo (LAC@HZIF-8-D) immobilization of catalytic activities for removing 2,4-dichlorophenol (2,4-DCP). The results showed higher catalytic activity for the laccase-immobilized LAC@HZIF-8 prepared using different methods than for the LAC@MZIF-8 sample, with 80% of 2,4-DCP removed under optimal conditions. These results could be attributable to the multistage structure of HZIF-8. The LAC@HZIF-8-D sample was stable and superior to LAC@HZIF-8-P, maintaining a 2,4-DCP removal efficiency of 80% after three recycles and demonstrating superior laccase thermostability and storage stability. Moreover, after loading with copper nanoparticles, the LAC@HZIF-8-D approach exhibited a 2,4-DCP removal efficiency of 95%, a promising finding for its potential use in environmental purification.

A Tiered Ecological Risk Assessment of Caffeine by Using Species Sensitivity Distribution Method in the Nansi Lake Basin.

Caffeine has been reported toxic to aquatic organisms, and it frequently occurs at relatively high concentrations in most of surface waters. However, it is difficult to control caffeine pollution because of the lack of Water Quality Criteria (WQC). In this study, species sensitivity distribution method and Log-normal model were applied to derive caffeine WQC as 83.7 ng/L. Meanwhile, concentrations of caffeine in the Nansi Lake basin were detected in 29 sampling sites, with the mean of 99.3 ng/L. The levels of caffeine in tributaries were higher than those in the lakes. In addition, a tied ecological risk assessment method was applied to assess the adverse effect of caffeine on aquatic system. The joint probability curve indicated that ecological risk might exist 3.1% of surface water in the study area, while 5% threshold (HC5) was set up to protect aquatic species. Generally, caffeine posted a low risk to aquatic organisms in the Nansi Lake basin.

Sequential Sol-Gel Self-Assembly and Nonclassical Gel-Crystal Transformation of the Metal-Organic Framework Gel.

Metal-organic framework (MOF) gel, an emerging subtype of MOF structure, is unique in formation and function; however, its evolutionary process remains elusive. Here, the evolution of a model gel-based MOF, UiO-66(Zr) gel, is explored by demonstrating its sequential sol-gel self-assembly and nonclassical gel-crystal transformation. The control of the sol-gel process enables the observation and characterization of structures in each assembly stage (phase-separation, polycondensation, and hindered-crystallization) and facilitates the preparation of hierarchical materials with giant mesopores. The gelation mechanism is tentatively attributed to the formation of zirconium oligomers. By further utilizing the pre-synthesized gel, the nonclassical gel-crystal transformation is achieved by the modulation in an unconventional manner, which sheds light on crystal intermediates and distinct crystallization motions ("growth and splitting" and "aggregation and fusion"). The overall sol-gel and gel-crystal evolutions of UiO-66(Zr) enrich self-assembly and crystallization domains, inspire the design of functional structures, and demand more in-depth research on the intermediates in the future.

Development and Assessment of a Novel Core Biopsy-Based Prediction Model for Pathological Complete Response to Neoadjuvant Chemotherapy in Women with Breast Cancer.

Purpose: Pathological complete response (pCR), the goal of NAC, is considered a surrogate for favorable outcomes in breast cancer (BC) patients administrated neoadjuvant chemotherapy (NAC). This study aimed to develop and assess a novel nomogram model for predicting the probability of pCR based on the core biopsy. Methods: This was a retrospective study involving 920 BC patients administered NAC between January 2012 and December 2018. The patients were divided into a primary cohort (769 patients from January 2012 to December 2017) and a validation cohort (151 patients from January 2017 to December 2018). After converting continuous variables to categorical variables, variables entering the model were sequentially identified via univariate analysis, a multicollinearity test, and binary logistic regression analysis, and then, a nomogram model was developed. The performance of the model was assessed concerning its discrimination, accuracy, and clinical utility. Results: The optimal predictive threshold for estrogen receptor (ER), Ki67, and p53 were 22.5%, 32.5%, and 37.5%, respectively (all p < 0.001). Five variables were selected to develop the model: clinical T staging (cT), clinical nodal (cN) status, ER status, Ki67 status, and p53 status (all p ≤ 0.001). The nomogram showed good discrimination with the area under the curve (AUC) of 0.804 and 0.774 for the primary and validation cohorts, respectively, and good calibration. Decision curve analysis (DCA) showed that the model had practical clinical value. Conclusions: This study constructed a novel nomogram model based on cT, cN, ER status, Ki67 status, and p53 status, which could be applied to personalize the prediction of pCR in BC patients treated with NAC.

Discovering dynamic plant enzyme complexes in yeast for novel alkaloid pathway identification from a medicinal plant kratom.

Discovering natural product biosynthetic pathways from medicinal plants is challenging and laborious, largely due to the complexity of the transcriptomics-driven pathway prediction process. Here we developed a novel approach that captures the protein-level connections between enzymes for pathway discovery with improved accuracy. We proved that heterologous protein-protein interaction screening in yeast enabled the efficient discovery of both dynamic plant enzyme complexes and the pathways they organize. This approach discovered complexes and pathways in the monoterpene indole alkaloid metabolism of a medicinal plant, kratom with high success rate. Screening using a strictosidine ß-D-glucosidase (MsSGD1) against 19 medium-chain dehydrogenase/reductases (MsMDRs) identified five MsSGD1-MsMDR complexes. Three out of the five interacting MsMDRs were then proven functional, while the remaining 14 non-interacting candidates did not show obvious activities. The work discovered three branched pathways by combining transcriptomics, metabolomics, and heterologous PPI screening and demonstrated a new plant pathway discovery strategy.

Leveraging yeast to characterize plant biosynthetic gene clusters.

Plant biosynthetic gene clusters (BGCs) contain multiple physically clustered non-homologous genes that encode enzymes catalyzing diverse reactions in one plant natural product biosynthetic pathway. A growing number of plant BGCs have emerged as an underlying resource for understanding plant specialized metabolism and evolution, but the characterization remains challenging. Recent studies have demonstrated that baker's yeast can serve as a versatile platform for the characterization of plant BGCs, from single-gene characterization to multiple genes and hitherto unknown putative BGC validation and elucidation. In this review, we will summarize the strategies and examples of the applications of yeast in plant BGC characterization and share our perspective on the development of a systematic pipeline to fully leverage yeast to advance the understanding of plant BGCs and plant natural product biomanufacturing.

Neoadjuvant Endocrine Therapy: A Potential Way to Make Cold Hormone Receptor-Rich Breast Cancer Hot.

BACKGROUND: Turning the "cold" tumor immune microenvironment into "hot" is a critical issue in cancer treatment today. Hormone receptor-rich breast cancer (HR+ BC) was previously considered immunologically quiescent. OBJECTIVE: This study aims to explore the immunomodulatory effects of endocrine therapy on HR+ BCs. METHODS: The infiltrations and alterations of the tumor immune microenvironment in HR+ BCs before, after 10-14 days, and after three months of neoadjuvant endocrine therapy were computationally analyzed according to MCP-counter, CIBERSORT, xCell algorithms, and gene-set enrichment analysis (GSEA). The primary microarray data were obtained from three HR+ BC gene expression datasets (GSE20181, GSE55374, and GSE59515). Single-sample GSEA of hallmark and immune response gene sets was performed to evaluate the correlation between suspected treatment response and activated immune pathways in tumors. RESULTS: Both immune and stromal cells were specifically recruited into the HR+ BCs who responded to the neoadjuvant endocrine therapy by letrozole. Besides the enhanced infiltrations of immunosurveillance-related cells such as CD8+ T cells, dendritic cells, and the activation of immune response-related signals, the immunosuppressive M2-like macrophages, as well as the expression of immune checkpoint genes like PDCD1, SIRPA, and some HLA genes, were also stimulated in responders. We identified four pretreatment indicators (the intrinsic luminal subtype, the estrogen response early/late pathway, and the epithelial-mesenchymal transition pathway) as potential predictors of both clinical response and the activation of the tumor immune microenvironment post letrozole. CONCLUSION: Neoadjuvant endocrine therapy showed a promising way to convert the immunologically "cold" HR+ BCs into "hot" tumors. This study provides new insights into the application of immunotherapy for HR+ BCs, especially those who respond to endocrine therapy.