Relationship Between Microstructural Alterations and Cognitive Decline After Whole-Brain Radiation Therapy for Brain Metastases: An Exploratory Whole-Brain MR Analysis Based on Neurite Orientation Dispersion and Density Imaging.

BACKGROUND: Cognitive impairment frequently occurs in patients with brain metastases (BM) after whole-brain radiotherapy (WBRT). It is crucial to explore the underlying mechanisms of cognitive impairment in BM patients receiving WBRT. PURPOSE: To detect brain microstructural alterations in patients after WBRT by neurite orientation dispersion and density imaging (NODDI), and evaluate the performance of microstructural alterations in predicting cognitive impairment. STUDY TYPE: Prospective. POPULATION: Twenty-six patients (seven female; mean age, 60.9 years). FIELD STRENGTH/SEQUENCE: 3-T, multi-shell diffusion-weighted single-shot echo-planar sequence. Three-dimensional magnetization-prepared rapid acquisition with gradient echo sequence. ASSESSMENT: Mini-mental state examination (MMSE) evaluations were conducted prior to, following, 1 and 3 months after WBRT. The diffusion data were collected twice, 1 week before and 1 week after WBRT. NODDI analysis was conducted to assess microstructural alterations in whole brain (orientation dispersion index, neurite density index, volume fraction of isotropic water molecules). Reliable change indices (RCI) of MMSE were used to measure cognitive decline. The performance of support vector machine models based on NODDI parameters and clinical features (prednisone usage, tumor volume, etc.) in predicting MMSE-RCI was evaluated. STATISTICAL TESTS: Paired t-test to assess alterations of NODDI measures and MMSE during follow-up. Statistical significance level of P-value <0.05. RESULTS: Significantly decreased MMSE score was found at 3 months after WBRT. After WBRT, corpus callosum, medial prefrontal cortex, limbic lobe, occipital lobe, parietal lobe, putamen, globus pallidus lentiform, and thalamus demonstrated damage in NODDI parameters. The predicted MMSE-RCI based on NODDI features was significantly associated with the measured MMSE-RCI at 1 month (R = 0.573; P = 0.003) and 3 months (R = 0.687; P < 0.0001) after WBRT. DATA CONCLUSION: Microstructural alterations in several brain regions including the middle prefrontal and limbic cortexes were observed in patients with BM following WBRT, which may contribute to subsequent cognitive decline. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Epidemiological characteristics of human metapneumovirus among children in Nanjing, China.

PURPOSE: The objective of this study was to examine the molecular epidemiology and clinical characteristics of HMPV infection among children with ARIs in Nanjing. METHODS: The respiratory samples were collected from 2078 children (≤ 14 years) with acute respiratory infections and were tested for HMPV using real-time RT-PCR. Amplification and sequencing of the HMPV G gene were followed by phylogenetic analysis using MEGA 7.0. RESULT: The detection rate of HMPV among children was 4.7% (97/2078), with a concentration in those under 5 years of age. Notably, the peak season for HMPV prevalence was observed in winter. Among the 97 HMPV-positive samples, 51.5% (50/97) were available for characterization of the HMPV G protein gene. Phylogenetic analysis indicated that the sequenced HMPV strains were classified into three sublineages: A2c111nt - dup (84.0%), B1 (2.0%), and B2 (14.0%). CONCLUSION: There was an incidence of HMPV among hospitalized children during 2021-2022 in Nanjing with A2c111nt - dup being the dominant strain. This study demonstrated the molecular epidemiological characteristics of HMPV among children with respiratory infections in Nanjing, China.

Membrane protein Bcsdr2 mediates biofilm integrity, hyphal growth and virulence of Botrytis cinerea.

Grey mould caused by Botrytis cinerea is a devastating disease responsible for large losses to agricultural production, and B. cinerea is a necrotrophic model fungal plant pathogen. Membrane proteins are important targets of fungicides and hotspots in the research and development of fungicide products. Wuyiencin affects the permeability and pathogenicity of B. cinerea, parallel reaction monitoring revealed the association of membrane protein Bcsdr2, and the bacteriostatic mechanism of wuyiencin was elucidated. In the present work, we generated and characterised ΔBcsdr2 deletion and complemented mutant B. cinerea strains. The ΔBcsdr2 deletion mutants exhibited biofilm loss and dissolution, and their functional activity was illustrated by reduced necrotic colonisation on strawberry and grape fruits. Targeted deletion of Bcsdr2 also blocked several phenotypic defects in aspects of mycelial growth, conidiation and virulence. All phenotypic defects were restored by targeted gene complementation. The roles of Bcsdr2 in biofilms and pathogenicity were also supported by quantitative real-time RT-PCR results showing that phosphatidylserine decarboxylase synthesis gene Bcpsd and chitin synthase gene BcCHSV II were downregulated in the early stages of infection for the ΔBcsdr2 strain. The results suggest that Bcsdr2 plays important roles in regulating various cellular processes in B. cinerea. KEY POINTS: • The mechanism of wuyiencin inhibits B. cinerea is closely associated with membrane proteins. • Wuyiencin can downregulate the expression of the membrane protein Bcsdr2 in B. cinerea. • Bcsdr2 is involved in regulating B. cinerea virulence, growth and development.

The trace that is valuable: serum copper and copper to zinc ratio for survival prediction in younger patients with newly diagnosed acute myeloid leukaemia.

PURPOSE: No data on predicting the survival of AML patients based on the level of trace elements in the serum have been presented to date. The aims of this prospective cohort study were as follows: (i) to evaluate the serum Cu and Zn levels in people from Northeast China, (ii) to assess the association between the serum Cu level (SCL) and Cu to Zn ratio (SCZR) and clinical and nutrition data, and (iii) to investigate the predictive values of the SCL and SCZR in newly diagnosed de novo AML patients. METHODS: A total of 105 newly diagnosed AML patients and 82 healthy controls were recruited. The serum Cu and Zn levels were determined by inductively coupled plasma spectrometry. The associations of SCL and SCZR with the survival of these AML patients were assessed by Cox proportional hazards models. RESULTS: Both SCL and SCZR were positively related to the blast percentage of bone marrow and C-reactive protein, negatively related to albumin level and CEBPA double mutation and were significantly associated with worse overall survival and disease-free survival. Meanwhile, patients with higher SCL had worse CTCAE levels, and patients with higher SCZR showed less complete remission during the first course of induction chemotherapy. Moreover, higher SCZR was positively associated with ELN risk stratification, and was negatively associated with haemoglobin level and prognostic nutritional index (PNI). CONCLUSION: The SCL and SCZR are associated with long-term survival in patients with newly diagnosed AML undergoing intensive induction and may serve as important predictive biomarkers.

A multi-criteria analysis framework for water transfers to improve the water environments under strong artificial interventions in highly urbanized areas.

Water transfer is an effective measure to enhance hydrodynamic and water quality in highly urbanized areas. The effect of water transfer in highly urbanized areas is affected by strong artificial interventions, and it is difficult to evaluate the improvement of multiple indicators of many sections after water transfer. At present, there is no analysis framework directly evaluates the improvement of water environment under strong artificial interventions, making it difficult to determine the optimal scheduling of hydraulic projects. This study constructed a multi-criteria analysis framework for evaluating the improvement of water environment including index layers of water quality improvement, hydrodynamic improvement and economic cost, and designed corresponding element layers for each index layer. The weights of each element were determined based on fuzzy analytical hierarchy process, and the fuzzy comprehensive evaluation method was used for comprehensive evaluation. The framework was applied in Xishan District in highly urbanized Taihu Lake Basin, and the results showed that the proposed framework could effectively determine the optimal scheduling of hydraulic projects. Water quality compliance rate for the optimal water transfer scheme achieved in Xishan District was 82%, average rate of water quality improvement was 31%, and proportion of cross-sections meeting the Class III water quality standard was 61%. Average flow velocity was 0.10 m/s, proportion of the optimal velocity was 39%, and proportion of stagnant sections was 32%. Furthermore, the impact of regional control projects on the effect of water transfer was much greater than local projects, consequently, the best scheduling mode for regional control projects should be first determined, and then the scheduling combination for local projects. This study can provide a new framework for the assessment of water transfers to improve the water environments and a scientific basis for the dispatching of hydraulic projects in Taihu Lake Basin.

Identification of a novel adjuvant loperamide that enhances the antibacterial activity of colistin against MCR-1-positive pathogens in vitro/vivo.

Severe infection with multidrug-resistant Enterobacterales caused by the plasmid-induced colistin resistance gene MCR-1 is a serious public health challenge. In this case, it is necessary and pressing to find a treatment to overcome antibiotic resistance. Here, we investigated the synergistic effect and mechanism of loperamide combined with colistin against MCR-1-positive pathogens. We evaluated the combined effect of loperamide and colistin using the checkerboard method and the time-kill experiment. The results showed that loperamide could enhance the bactericidal ability of colistin, and this combination regimen could completely kill the tested bacteria within 4 h. Subsequently, spectrofluorimetric methods were used to explore the mechanism of loperamide combined with colistin. The results indicated that the mode of action of loperamide combined with colistin was found to involve mechanical disruption of the membrane. Furthermore, molecular simulation and microscale thermophoresis results revealed that loperamide reduced the impact of MCR-1 protein by directly binding to its active site. In addition, the combined regimen of loperamide and colistin effectively reduced the bacterial load in the thighs of mice while increasing the protection rate by 70%. In short, as a potential lead compound, loperamide can enhance the killing effect of colistin on pathogenic Enterobacterales carrying MCR-1 by causing membrane damage and inhibiting MCR-1 protein activity.

Nonintrusive wind blade fault detection using a deep learning approach by exploring acoustic information.

Various physical characteristics, including ultrasonic waves, active acoustic emissions, vibrations, and thermal imaging, have been used for blade fault detection. In this work, we propose using the sound produced by spinning wind blades to identify faults. To the best of our knowledge, passive acoustic information has not yet been explored for this task. In particular, we develop three networks targeting different scenarios. The main contributions of this work are threefold. First, when normal and aberrant data are available for supervised learning, an attention-convolutional recurrent neural network is designed to show the feasibility of using passive sound information to conduct fault detection. Second, in the absence of abnormal training data, we build a normal-encoder network to learn the distributions of normal data through semisupervised learning, which avoids the requirement of abnormal training data. Third, when multiple devices are used to collect the data, due to different properties of devices, there is a domain mismatch issue. To overcome this, we create an adversarial domain adaptive network to close the gap between the source and target domains. Acoustic signal datasets of actual wind turbine operations are collected to evaluate our fault detection systems. The findings demonstrate that the proposed systems offer high classification accuracy and indicate the feasibility of passive acoustic signal-based wind turbine blade fault detection with one step close to automatic detection.

Induced Defense Response in Soybean to Sclerotinia sclerotiorum Using Wuyiencin from Streptomyces albulus CK-15.

Sclerotinia sclerotiorum (Lib) de Bary, a destructive fungal pathogen with an extensive host range, causes major economic losses to crop production activities globally. Streptomyces spp. produce secondary metabolites with diverse structures and biological activities with potential applications in the control of crop disease. This study explored the potential application of wuyiencin, a secondary metabolite of Streptomyces albulus CK-15, to induce defense responses in soybean against S. sclerotiorum. Lesion size was reduced by nearly 60% in wuyiencin-treated soybean plants compared with plants infected with S. sclerotiorum only in greenhouse experiments. Wuyiencin induced callose deposition at 6 h postinoculation and increased reactive-oxygen-scavenging enzyme activities, including superoxide dismutase, catalase, and peroxidase. Moreover, wuyiencin inoculated before S. sclerotiorum infection significantly increased polyphenol oxidase, phenylalanine ammonia lyase, chitinase, and ß-1,3-glucanase activity, suggesting their involvement in soybean defense responses to S. sclerotiorum. Further, qRT-PCR results showed expression levels of the hormone signaling markers CO11, MYC2, PR4, PR1, NPR1, and ERF1 were upregulated in infected leaves treated with wuyiencin.

Enhancing wuyiencin productivity of Streptomyces albulus (CK15) by mutagenesis breeding with atmospheric and room temperature plasma.

Streptomyces species are known for their ability to efficiently produce secondary metabolites, including various antibiotics. Wuyiencin, an antibiotic produced by Streptomyces albulus CK15, is commonly used in agriculture to control fungal diseases in crops and vegetables. In this study, we utilized atmospheric and room temperature plasma (ARTP) mutagenesis to generate mutant S. albulus strains with improved fermentation capabilities for wuyiencin production. After mutagenizing the wild-type S. albulus CK15 strain once and conducting two rounds of antimicrobial screening, three genetically stable mutants (M19, M26, and M28) were identified. These mutants showed increased wuyiencin production by 17.4%, 13.6%, and 18.5% in comparison to the CK15 strain in flask culture, respectively. The M28 mutant exhibited the highest wuyiencin activity, producing 1443.0 ± 134.6 U/mL in flask culture and 1673.8 ± 127.4 U/mL in a 5 L fermenter. These results demonstrate that ARTP is an efficient tool for microbial mutation breeding and improving wuyiencin production.

Aggressive disseminated Rhizomucor pusillus infection in a Ph-like acute lymphoblastic leukemia patient: Early detection by cell-free DNA next-generation sequencing.

Disseminated Rhizomucor pusillus infection is a very rare but fatal complication in immunocompromised patients, because of aggressive clinical process with delayed diagnosis by routine laboratory tests. Recently, cell-free DNA next-generation sequencing (cfDNA NGS) has been used for the timely detection of infectious pathogens including mucormycosis. Herein, we described an 18-year-old male with Philadelphia-like acute lymphoblastic leukemia who received a timely diagnosis of R. pusillus infection by cell-free DNA next-generation sequencing, and confirmed by silver staining and qPCR on biopsy tissue. To the best of our knowledge, this was the first case of disseminated R. pusillus infection detected by cfDNA NGS and confirmed by histology in an adult leukemia patient. In addition, this case was supposed to be the most extensive R. pusillus infection diagnosed, involving the lung, skin, liver, kidney, spleen and brain, and the only one case who survived the infection had a favorable outcome through treatment with liposome amphotericin B sequential posaconazole. This case suggested that cfDNA NGS could be used to successfully detect rare pathogen infections, and this was especially important for R. pusillus because timely diagnosis and effective treatment could improve the prognosis of this kind of patient.

Evaluation of the Inhibitory Effects of Wuyiencin, a Secondary Metabolite of Streptomyces albulus CK-15, Against Sclerotinia sclerotiorum In Vitro.

Sclerotinia sclerotiorum (Lib.) de Bary, a destructive fungal pathogen with an extensive host range, causes various diseases with the potential to cause huge economic losses to crops worldwide. Streptomyces species produce secondary metabolites with variable structures and biological activities that offer possible control methods for crop diseases. Herein, we evaluated the inhibitory effects of wuyiencin, a secondary metabolite of Streptomyces albulus CK-15, against S. sclerotiorum. The results showed that wuyiencin markedly inhibited mycelial growth and germination and the formation of sclerotia. It also increased cell membrane permeability, resulting in leakage of intracellular substances in pathogen mycelia. Wuyiencin markedly decreased oxalic acid content and the activities of polygalacturonase and pectin methyl-galacturonic enzymes. Moreover, it downregulated Nox1, ITL, pph1, Caf1, and sca1, all genes related to growth and infection. Lesions were smaller and less pronounced on soybean (Glycine max [L.] Merr.) leaves pretreated with wuyiencin in vitro, and the inhibition rate reached 78.36%. The results suggest that wuyiencin holds promise for the management of diseases caused by S. sclerotiorum, and the findings provide clues on the mechanism of action.

Effect of toyF on wuyiencin and toyocamycin production by Streptomyces albulus CK-15.

Streptomyces albulus CK-15 produces various secondary metabolites, including the antibiotics wuyiencin and toyocamycin, which can reportedly control a broad range of plant fungal diseases. The production of these nucleoside antibiotics in CK-15 is regulated by two biosynthesis gene clusters. To investigate the potential effect of toyocamycin biosynthesis on wuyiencin production, we herein generated S. albulus strains in which a key gene in the toyocamycin biosynthesis gene cluster, namely toyF, was either deleted or overexpressed. The toyF deletion mutant ∆toyF did not produce toyocamycin, while the production of wuyiencin increased by 23.06% in comparison with that in the wild-type (WT) strain. In addition, ΔtoyF reached the highest production level of wuyiencin 4 h faster than the WT strain (60 h vs. and 64 h). Further, toyocamycin production by the toyF overexpression strain was two-fold higher than by the WT strain, while wuyiencin production was reduced by 29.10%. qRT-PCR showed that most genes in the toyocamycin biosynthesis gene cluster were expressed at lower levels in ∆toyF as compared with those in the WT strain, while the expression levels of genes in the wuyiencin biosynthesis gene cluster were upregulated. Finally, the growth rate of ∆toyF was much faster than that of the WT strain when cultured on solid or liquid medium. Based on our findings, we report that in industrial fermentation processes, ∆toyF has the potential to increase the production of wuyiencin and reduce the timeframe of fermentation.

Characterization and monitoring of charge variants of a recombinant monoclonal antibody using microfluidic capillary electrophoresis-mass spectrometry.

Rigorous characterization of biotherapeutics, and monoclonal antibodies in particular, is a challenging task in terms of ensuring safety, efficacy, and potency of a therapeutic agent because of structural heterogeneity during cell culture, purification and storage. In this work, we used microfluidic capillary electrophoresis-mass spectrometry to analyze intact monoclonal antibody and assess the root cause of increases in acidic and basic variants under stress at high temperature. The antibody was analyzed at multiple levels, including its intact state under native conditions, and subunit and peptide levels. The normal and degraded antibodies at different time points were characterized and compared with each other. We concluded that the basic variants in the unstressed sample were produced C-terminal amidation, while the acidic variants were produced by deamidation. In stressed samples, change in the acidic and main peaks were caused by deamidation, and changes in the basic peaks were caused by both deamidation and oxidation. These results demonstrate that microfluidic capillary electrophoresis-mass spectrometry (CE-MS) is a powerful direct and generic tool for separation and identification of charge heterogeneity of biotherapeutics.

iTRAQ-based proteomic analysis reveals the mechanisms of Botrytis cinerea controlled with Wuyiencin.

BACKGROUND: Grey mould is an important plant disease worldwide, caused by Botrytis cinerea, resulting in serious economic loss. Wuyiencin, a low toxicity, high efficiency, and broad-spectrum agricultural antibiotic, has been demonstrated effectiveness against B. cinerea. RESULTS: Wuyiencin treatment inhibited growth and sporulation of B. cinerea, specifically altering hypha morphology and intracellular structures. These changes were accompanied by differential expression (fold change > 2.0) of 316 proteins identified by iTRAQ-labelling LC-MS/MS analysis (P < 0.05). Up-regulation of 14 proteins, including carbohydrate metabolism proteins and cell wall stabilization proteins, was validated by parallel reaction monitoring (PRM). Down-regulation of 13 proteins was validated by PRM, including regulators of energy metabolism, nucleotide/protein synthesis, and the biosynthesis of mediators of plant stress and decay. CONCLUSION: Our results confirm the inhibitory biological effects of wuyiencin on B. cinereal and elaborate on the differentially expressed proteins and associated pathways implicated in the capacity of wuyiencin to debilitate the growth and pathogenicity of grey mould. This study provides validated candidates for further targeted exploration with the goal of optimizing wuyiencin as a safe, low-toxicity agent for biological control.

Indole-3-acetic acid production by Streptomyces fradiae NKZ-259 and its formulation to enhance plant growth.

BACKGROUND: Indole-3-acetic acid (IAA) is produced by microorganisms and plants via either tryptophan-dependent or tryptophan-independent pathways. Herein, we investigated the optimisation of IAA production by Streptomyces fradiae NKZ-259 and its formulation as a plant growth promoter to improve economic and agricultural development. RESULTS: The maximum IAA yield achieved using optimal conditions was 82.363 µg/mL in the presence of 2 g/L tryptophan after 6 days of incubation. Thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC) analysis of putative IAA revealed an RF value of 0.69 and a retention time of 11.842 min, comparable with the IAA standard. Regarding product formulation, kaolin-based powder achieved a suspension rate of 73.74% and a wetting time of 80 s. This carrier exhibited good shelf life stability for NKZ-259, and the cell population did not decrease obviously over 4 months of storage at 4 °C. In vivo analysis of plant growth promotion showed that tomato seedlings treated with kaolin powder containing NKZ-259 cells displayed a significant increase in root and shoot length of 7.97 cm and 32.77 cm, respectively, and an increase in fresh weight and dry weight of 6.72 g and 1.34 g. Compared to controls, plant growth parameters were increased almost it two-fold. CONCLUSION: Optimising the culture conditions resulted in an almost four-fold increase in IAA secretion by NKZ-259 cells. The results clearly demonstrate that S. fradiae NKZ-259 holds great potential for plant growth promotion and IAA production. Furthermore, kaolin-based powder is an effective carrier for NKZ-259 cells and may be useful for commercial applications.

The antifungal action mode of the rice endophyte Streptomyces hygroscopicus OsiSh-2 as a potential biocontrol agent against the rice blast pathogen.

Microbial antagonists and their bioactive metabolites provide one of the best alternatives to chemical pesticides to control crop disease for sustainable agriculture and global food security. The rice endophyte Streptomyces hygroscopicus OsiSh-2, with remarkable antagonistic activity towards the rice blast fungus Magnaporthe oryzae, was reported in our previous study. The present study deciphered the possible direct interaction mode of OsiSh-2 against M. oryzae. An in vitro antibiotic assay for OsiSh-2 culture filtrate revealed strong suppression of mycelial growth, conidial germination and appressorial formation of M. oryzae. Meanwhile, severe morphological and internal abnormalities in M. oryzae hyphae were observed under a scanning electron microscope and transmission electron microscope. Foliar treatment of rice seedlings by OsiSh-2 culture filtrate in the greenhouse and in the field showed 23.5% and 28.3% disease reduction, respectively. Correspondingly, OsiSh-2 culture filtrate could induce disorganized chitin deposition in the cell wall and lowered ergosterol content in the cell membrane of M. oryzae. Additionally, cell wall integrity pathway activation, large cell electrolytes release, reactive oxygen species accumulation and tricarboxylic acid cycle-related enzyme activity changes were found in M. oryzae. All these results suggested that the direct antagonistic activity of OsiSh-2 against M. oryzae may be attributed to damaging the integrity of the cell wall and membrane and disrupting mitochondrial function in the pathogen.

Dynamic and epistatic QTL mapping reveals the complex genetic architecture of waterlogging tolerance in chrysanthemum.

MAIN CONCLUSION: 37 unconditional QTLs, 51 conditional QTLs and considerable epistatic QTLs were detected for waterlogging tolerance, and six favourable combinations were selected accelerating the possible application of MAS in chrysanthemum breeding. Chrysanthemum is seriously impacted by soil waterlogging. To determine the genetic characteristics of waterlogging tolerance (WAT) in chrysanthemum, a population of 162 F1 lines was used to construct a genetic map to identify the dynamic and epistatic quantitative trait loci (QTLs) for four WAT traits: wilting index (WI), dead leaf ratio (DLR), chlorosis score (Score) and membership function value of waterlogging (MFVW). The h B2 for the WAT traits ranged from 0.49 to 0.64, and transgressive segregation was observed in both directions. A total of 37 unconditional consensus QTLs with 5.81-18.21% phenotypic variation explanation (PVE) and 51 conditional consensus QTLs with 5.90-24.56% PVE were detected. Interestingly, three unconditional consensus QTLs were consistently identified across different stages, whereas no conditional consensus QTLs were consistently expressed. In addition, considerable epistatic QTLs, all with PVE values ranging from 0.01 to 8.87%, were detected by a joint analysis of WAT phenotypes. These results illustrated that the QTLs (genes) controlling WAT were environmentally dependent and selectively expressed at different times and indicated that both additive and epistatic effects underlie the inheritance of WAT in chrysanthemum. The findings of the current study provide insights into the complex genetic architecture of WAT, and the identification of favourable alleles represents an important step towards the application of molecular marker-assisted selection (MAS) and QTL pyramiding in chrysanthemum WAT breeding programmes.

Comprehensive review on the elaboration of payloads derived from natural products for antibody-drug conjugates.

Antibody-drug conjugates (ADCs) have arisen as a promising class of biotherapeutics for targeted cancer treatment, combining the specificity of monoclonal antibodies with the cytotoxicity of small-molecule drugs. The choice of an appropriate payload is crucial for the success development of ADCs, as it determines the therapeutic efficacy and safety profile. This review focuses on payloads derived from natural products, including cytotoxic agents, DNA-damaging agents, and immunomodulators. These offer several advantages such as diverse chemical structures, unique mechanism of actions, and potential for improved therapeutic index. Challenges and opportunities associated with their development were highlighted. This review underscores the significance of natural product payloads in the elaboration of ADCs, which serves as a valuable resource for researchers involved in developing and optimizing next-generation ADCs for cancer treatment.

Efficacy and safety of combining short-course neoadjuvant chemoradiotherapy with envafolimab in locally advanced rectal cancer patients with microsatellite stability: A phase II PRECAM experimental study.

BACKGROUND: Conventional neoadjuvant chemoradiotherapy (nCRT) yields a pathologic complete response (pCR) rate of 15%-30% for locally advanced rectal cancer (LARC). This study ventures to shift this paradigm by incorporating short-course nCRT with immunotherapy, specifically Envafolimab, to achieve improved treatment efficacy and possibly redefine the standard of care for LARC. MATERIALS AND METHODS: The PRECAM study is a prospective, single-arm, phase 2 clinical trial for LARC in patients with microsatellite stable (MSS) tumors. Participants received short-course radiotherapy (25Gy/5f), followed by two cycles of CAPEOX chemotherapy and six weekly doses of Envafolimab, a PD-L1 antibody, before total mesorectal excision surgery. The primary endpoint was the pCR rate. RESULTS: From April to December 2022, 34 patients were enrolled, of whom 32 completed the study, each diagnosed with an MSS rectal adenocarcinoma. All patients underwent preoperative CRT combined with Envafolimab. Remarkably, a pCR rate of 62.5% (20/32) was attained, and a significant pathologic response rate of 75% (24/32) was achieved. Additionally, 21 of 32 participants achieved a neoadjuvant rectal (NAR) score below 8, suggesting an effective treatment response. Common adverse events included tenesmus (78.1%), diarrhea (62.5%), and leukocyte decrease (40.6%). Two Grade 3 adverse events were noted, one related to liver function abnormality and the other to a decrease in platelet count. Surgical procedures were performed in all cases, with minor complications, including ileus, infections, and anastomotic leakage. As of this report, there have been no reported cases of recurrence or death during the follow-up period, ranging from 12 to 20 months. CONCLUSION: In LARC patients exhibiting MSS tumors, combining short-course nCRT with Envafolimab demonstrated favorable efficacy, leading to a significant pCR rate. Minor adverse effects and surgical complications were observed. These preliminary but promising results underscore the potential of this approach and call for further exploration and validation through a randomized controlled trial.

Impact of Varicella Immunization and Public Health and Social Measures on Varicella Incidence: Insights from Surveillance Data in Shanghai, 2013-2022.

To evaluate the impact of a two-dose VarV program on varicella incidence among the whole population, considering the influence of public health and social measures (PHSMs), we extracted surveillance data on varicella cases during 2013-2022 in Minhang, Shanghai. Then, we estimated the incidence trend of varicella through interrupted time-series analyses and quantified the impact of the immunization program and PHSMs using Serfling regression. We also explored the associations between PHSMs and varicella cases. The implementation of the two-dose VarV strategy was followed by a significant decrease in varicella incidence (-1.84% per month). After one year of the program, varicella incidence was estimated at a 45.25% reduction, which was higher in children (59.12% and 54.09%) than in adults (19.49%). The decrease attributed to PHSMs was 31.26% during 2020-2022, and school closing was identified as the most relevant PHSM (b = -8.03 cases, r = -0.67 with a 1-week lag). These findings indicate that the two-dose immunization program has more effectively reduced the varicella incidence compared with the one-dose vaccine, and interventions like school closings are also encouraged to serve as supplementary measures to prevent varicella epidemics.