Multi-Stimuli-Responsive, Topology-Regulated, and Lignin-Based Nano/Microcapsules from Pickering Emulsion Templates for Bidirectional Delivery of Pesticides.

The increasing demand for improving pesticide utilization efficiency has prompted the development of sustainable, targeted, and stimuli-responsive delivery systems. Herein, a multi-stimuli-responsive nano/microcapsule bidirectional delivery system loaded with pyraclostrobin (Pyr) is prepared through interfacial cross-linking from a lignin-based Pickering emulsion template. During this process, methacrylated alkali lignin nanoparticles (LNPs) are utilized as stabilizers for the tunable oil-water (O/W) Pickering emulsion. Subsequently, a thiol-ene radical reaction occurs with the acid-labile cross-linkers at the oil-water interface, leading to the formation of lignin nano/microcapsules (LNCs) with various topological shapes. Through the investigation of the polymerization process and the structure of LNC, it was found that the amphiphilicity-driven diffusion and distribution of cyclohexanone impact the topology of LNC. The obtained Pyr@LNC exhibits high encapsulation efficiency, tunable size, and excellent UV shielding to Pyr. Additionally, the flexible topology of the Pyr@LNC shell enhances the retention and adhesion of the foliar surface. Furthermore, Pyr@LNC exhibits pH/laccase-responsive targeting against Botrytis disease, enabling the intelligent release of Pyr. The in vivo fungicidal activity shows that efficacy of Pyr@LNC is 53% ± 2% at 14 days postspraying, whereas the effectiveness of Pyr suspension concentrate is only 29% ± 4%, and the acute toxicity of Pyr@LNC to zebrafish is reduced by more than 9-fold compared with that of Pyr technical. Moreover, confocal laser scanning microscopy shows that the LNCs can be bidirectionally translocated in plants. Therefore, the topology-regulated bidirectional delivery system LNC has great practical potential for sustainable agriculture.

Seed and Soil: Consensus Molecular Subgroups (CMS) and Tumor Microenvironment Features Between Primary Lesions and Metastases of Different Organ Sites in Colorectal Cancer.

Purpose: Consensus molecular subtypes (CMS) are mainly used for biological interpretability and clinical stratification of colorectal cancer (CRC) in primary tumors (PT) but few in metastases. The heterogeneity of CMS distribution in metastases and the concordance of CMS between PT and metastases still lack sufficient study. We used CMS to classify CRC metastases and combine it with histopathological analysis to explore differences between PT and distant metastases. Patients and Methods: We obtained gene expression profiles for 942 PT samples from TCGA database (n=376) and GEO database (n=566), as well as 442 metastasis samples from GEO database. Among these, 765 PT samples and 442 metastasis samples were confidently identified with CMS using the "CMS classifier" and enrolled for analysis. Clinicopathological manifestation and CMS classification of CRC metastases were assessed with data from GEO, TCGA, and cBioPortal. Overall, 105 PT-metastasis pairs were extracted from 10 GEO datasets to assess CMS concordance. Tumor microenvironment (TME) features between PT and metastases were analyzed by immune-stromal infiltration with ESTIMATE and xCell algorithms. Finally, TME features were validated with multiplex immunohistochemistry in 27 PT-metastasis pairs we retrospectively collected. Results: Up to 64% of CRC metastases exhibited concordant CMS groups with matched PT, and the TME of metastases was similar to that of PT. For most common distant metastases, liver metastases were predominantly CMS2 and lung and peritoneal metastases were mainly CMS4, highlighting "seed" of tumor cells of different CMS groups had a preference for metastasis to "soil" of specific organs. Compared with PT, cancer-associated fibroblasts (CAF) reduced in liver metastases, CD4+T cells and M2-like macrophages increased in lung metastases, and M2-like macrophages and CAF increased in peritoneal metastases. Conclusion: Our findings underscore the importance of CMS-guided specific organ monitoring and treatment post-primary tumor surgery for patients. Differences in immune-stromal infiltration among different metastases provide targeted therapeutic opportunities for metastatic CRC.

Copper-coordinated nanoassemblies based on photosensitizer-chemo prodrugs and checkpoint inhibitors for enhanced apoptosis-cuproptosis and immunotherapy.

Cuproptosis is a recently identified copper-dependent form of nonapoptotic cell death and holds great prospect in cancer treatment. One of the most intriguing aspects of cuproptosis is its ability to synergize with apoptosis-based cancer treatments. Herein, we presented a novel approach using copper-coordinated nanoassemblies (CCNAs) that were constructed by incorporating a photosensitizer Zinc Phthalocyanine (ZnPc)-chemotherapeutic (DOX) prodrug with a thioketal (TK) spacer and an IDO inhibitor (1-methyl tryptophan, 1-MT) as building blocks for Cu2+-coordination self-assembly to achieve combinational apoptosis-cuproptosis and immunotherapy. Upon NIR laser irradiation, the ZnPc component of CCNAs exhibited a photodynamic effect that generated reactive oxygen species (ROS). This triggered the release of DOX, leading to enhanced tumor cell apoptosis. Additionally, the presence of Cu2+ in the CCNAs not only enhanced the photodynamic process by catalyzing oxygen generation but also promoted the aggregation of toxic mitochondrial proteins, leading to cell cuproptosis. Importantly, the intensified cuproptosis-apoptosis effect triggered an immunogenic cell death (ICD) response. The released 1-MT complemented this response by reversing the immunosuppressive tumor microenvironment (ITM), synergistically amplifying anti-tumor immunity and suppressing the growth of primary and distant tumors. The findings of this study provide a new perspective on potential cancer treatments based on cuproptosis-apoptosis synergistic immunotherapy and stimulate further research in the design of advanced metal-coordinated nanomedicines. STATEMENT OF SIGNIFICANCE: The combination of cuproptosis and apoptosis that act with different mechanisms holds enormous potential in cancer treatment. Here, copper-coordinated nanoassemblies (CCNAs) based on photosensitizer-chemo prodrugs and checkpoint inhibitors were constructed for mediating cuproptosis-apoptosis and subsequently promoting cancer immunotherapy. CCNAs not only promoted the photodynamic effect and activation of chemotherapy through catalyzing the generation of oxygen but also induced toxic mitochondrial protein aggregation, leading to cell cuproptosis. These synergistic antitumor effects triggered robust immune responses with the aid of immune checkpoint blockade, almost eradicating primary tumors and inhibiting distant tumors by around 83 % without systemic toxicity.

Comparison of breast-conserving surgery without radiotherapy and mastectomy in the treatment of elderly patients with early breast cancer: A PSM and SEER database study.

BACKGROUND: At present, there is no research on which surgical method can lead to a better prognosis in elderly patients with early breast cancer. The purpose of this study was to establish a nomogram to predict the survival outcome of elderly patients with early breast cancer and to compare the prognosis of the breast-conserving surgery (BCS) group who did not receive postoperative radiotherapy and the mastectomy group through risk stratification. METHODS: This study included patients with early breast cancer aged ≥70 years from the Surveillance, Epidemiology, and End Results database (n = 20,520). The group was randomly divided into a development cohort (n = 14,363) and a validation cohort (n = 6157) according to a ratio of 7:3. Risk factors affecting overall survival (OS) and breast-cancer-specific survival (BCSS) were analyzed using univariate and multivariate Cox regression. Present results were obtained by constructing nomograms and risk stratifications. Nomograms were evaluated by the concordance index and calibration curve. Kaplan-Meier curves were established based on BCSS and analyzed using the log-rank test. RESULTS: Multivariate Cox regression results showed that age, race, pathological grade, T and N stages, and progesterone receptor (PR) status were independent risk factors for OS and BCSS in the BCS group and mastectomy group. Subsequently, they were incorporated into nomograms to predict 3- and 5-year OS and BCSS in patients after BCS and mastectomy. The concordance index was between 0.704 and 0.832, and the nomograms also showed good calibration. The results of risk stratification showed that there was no survival difference between the BCS group and the mastectomy group in the low-risk and high-risk groups. In the middle-risk group, BCS improved the BCSS of patients to a certain extent. CONCLUSION: This study constructed a well-performing nomogram and risk stratification model to assess the survival benefit of BCS without postoperative radiotherapy in elderly patients with early breast cancer. The results of the study can help clinicians analyze the prognosis of patients and the benefits of surgical methods individually.

The Application of Mixed Reality to Sentinel Lymph Node Biopsy in Breast Cancer.

OBJECTIVE: To explore the value of mixed reality (MR) in sentinel lymph node biopsy (SLNB) in patients with breast cancer. METHODS: A total of 300 patients with breast cancer who underwent SLNB enrolled and were randomly divided into two groups. In group A, only dye (an injection of methylene blue) was used to detect sentinel lymph nodes, while in group B MR was used for positioning in addition to dye. (MR localization method: Before the surgery, we built a 1:1 3D reconstruction model based on the patient's CT or MRI original data, and after the patient was injected with dye, we completed MR localization by overlapping the pre-marked image with the model.) RESULTS: During surgery, the detection time in group B was significantly shorter than in group A (3.62 ± 1.20 vs.7.87 ± 1.86; p < 0.001). At 1-month post-surgery follow-up, the incidence of pain in group B was lower than that in group A (2.70 vs. 8.28%, p = 0.036). The incidence of upper limb dysfunction was lower in group B than in group A (2.03 vs. 8.97%, p = 0.009). In terms of the incidence of pain, group B was better than group A (0.68 vs. 3.45%, p = 0.094). The satisfaction of the two groups was scored, and the results showed that group B was better than group A (4.04 ± 0.91 vs.3.32 ± 0.94, p < 0.001). CONCLUSION: The application of MR to SLNB in breast cancer can significantly reduce the detection time and the occurrence of complications and improve patient satisfaction.

Advances in stimuli-responsive systems for pesticides delivery: Recent efforts and future outlook.

Effective pest management for enhanced crop output is one of the primary goals of establishing sustainable agricultural practices in the world. Pesticides are critical in preventing biological disasters, ensuring crop productivity, and fostering sustainable agricultural production growth. Studies showed that crops are unable to properly utilize pesticides because of several limiting factors, such as leaching and bioconversion, thereby damaging ecosystems and human health. In recent years, stimuli-responsive systems for pesticides delivery (SRSP) by nanotechnology demonstrated excellent promise in enhancing the effectiveness and safety of pesticides. SRSP are being developed with the goal of delivering precise amounts of active substances in response to biological needs and environmental factors. An in-depth analysis of carrier materials, design fundamentals, and classification of SRSP were provided. The adhesion of SRSP to crop tissue, absorption, translocation in and within plants, mobility in the soil, and toxicity were also discussed. The problems and shortcomings that need be resolved to accelerate the actual deployment of SRSP were highlighted in this review.

Colon cancer patient with long-term colon stent placement: Case report and literature review.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer mortality globally. Large bowel obstruction (occurring in 15-30% of patients with CRCs) accounts for approximately 80% of medical emergencies related to CRC. Currently, there is no standard treatment of this condition. The European Society of Gastrointestinal Endoscopy (ESGE) recommends self-expandable metal stent (SEMS) as a bridge (two weeks) to surgery for left-sided obstructing colon cancer. In the present report, we describe an 81-year-old male with colon cancer who underwent colon stent placement for 32 months, but later underwent radical resection. A follow-up of more than four-months revealed that his condition was normal. The history as well as application and advantages of SEMS are discussed in this report.

A comparative study on ultrasound-guided elite, Mammotome, and core needle biopsy for diagnosing malignant breast masses.

Introduction: The present study aims to clarify the advantages and disadvantages of elite biopsy, to provide a reference for selecting the puncture method. Material and methods: A total of 802 patients with a BI-RADS grade ≥ 4, as evaluated by the molybdenum target, and measurable lesions revealed by colour Doppler ultrasound, who were admitted at our department from January 2017 to January 2018, were enrolled in the present study. These patients were randomly divided into three groups: elite, Mammotome and core needle biopsy groups. The pathological underestimation rate, diagnostic accordance rate, haematoma incidence rate, and costs of these three biopsy methods were compared. Results: The difference in diagnostic accordance rates between the elite biopsy group and core needle biopsy group was statistically significant (98.9% vs. 94.7%, p = 0.003), as well as between the Mammotome biopsy group and core needle biopsy group (99.6% vs. 94.7%, p < 0.001). The difference in pathological underestimation rates between the elite biopsy group and core needle biopsy group was statistically significant (7.2% vs. 37.3%, p < 0.001), as well as between the Mammotome biopsy group and core needle biopsy group (1.6% vs. 7.2%, p < 0.001). The difference between the Mammotome biopsy group and elite biopsy group was not statistically significant. The incidence of haematoma in the Mommotome, elite, and core needle groups was 15.9%, 13%, and 21.7%, respectively (13% vs. 21.7%, p = 0.021). Conclusions: Elite biopsy has a low rate of pathological underestimation and low incidence of haematoma, can improve the breast conserving rate, and has an affordable cost. As a biopsy method with high accuracy, safety, and economy, elite biopsy can be widely used in clinics.

3D, eco-friendly metal-organic frameworks@carbon nanotube aerogels composite materials for removal of pesticides in water.

To alleviate the secondary risks of using metal-organic frameworks (MOFs) nanoparticles as adsorbent, a novel method of loading two MOFs (ZIF-8 or UiO66-NH2) on the carbon nanotube aerogels (MPCA) by in situ nucleation and growth of MOFs nanoparticles onto carbon nanotubes were developed. The prepared MOFs@MPCA aerogels were well characterized via SEM, TEM, EDS, FT-IR, XRD and XPS to reveal the microstructure and formation mechanism of MOF@MPCA. Besides, the hydrophilia, mechanical property and thermostability of MOF@MPCA were investigated. The results showed that MOF@MPCA had good hydrophilia, compression resilience and thermostability. The study on the ability to adsorb herbicides (chipton and alachlor) showed that the adsorption capacity of MOF@MPCA was stronger compared with single MOFs nanoparticles, which indicated that there was a synergistic effect between MOFs and MPCA. The equilibrium adsorption capacity of chipton adsorbed by UiO66-NH2@MPCA was 227.3 mg/g, and can be expediently reused for 5 cycles without a significant decrease in adsorption performance. Moreover, the results of biosafety experiments showed that MPCA can reduce the risk of MOFs nanoparticles leakage into the environment and accumulation in organisms. This work can provide a new research idea, which has potential applications to remove pollutants effectively and safely from the environment.

Comparison of curative effects between mammotome-assisted minimally invasive resection (MAMIR) and traditional open surgery for gynecomastia in Chinese patients: A prospective clinical study.

To analyze and compare prospectively the curative effects between mammotome-assisted minimally invasive resection (MAMIR) and traditional open surgery (TOS) for gynecomastia in Chinese male patients, a total of 60 patients suffering from grade I and II gynecomastia, evaluated by automated whole-breast ultrasound (AWBU), were recruited and randomly divided into TOS and MAMIR groups (each n = 30). The postoperative scar size, healing time, patient hospital stay, postoperative satisfaction, postoperative pain, and complications including edema and bruising were analyzed. The participants were followed up for 1 week, 1 month, 6 months, and 1 year after surgery. Compared with patients who received TOS, patients in the MAMIR group had significantly smaller scar sizes (0.40 ± 0.08 cm vs 5.34 ± 0.38 cm, P < 0.01), shorter healing times (3.67 ± 0.71 days vs 7.90 ± 0.92 days, P < 0.01), and hospitalization (2.60 ± 0.62 vs 7.17 ± 0.83 days, P < 0.01), as well as higher postoperative satisfaction (4.70 ± 0.60 vs 3.20 ± 0.55 scores, P < 0.01), respectively. Patients in the MAMIR group experienced postoperative mild pain significantly more often than those in the TOS group (6.70 ± 1.06 vs 4.13 ± 0.78 scores, P < 0.01, respectively), but with significantly less postoperative severe pain (53.33% vs 0.00%, P < 0.000). While the incidence rate of edema and bruises was significantly higher in the MAMIR group compared with the TOS group (47% vs 17%, P = 0.013 and 54% vs 20%, P = 0.007, respectively). MAMIR had advantages for curative effects compared with traditional open surgery. However, the recurrence rate in patients needs to be further studied.

Development of Multifunctional Avermectin Poly(succinimide) Nanoparticles to Improve Bioactivity and Transportation in Rice.

Avermectin (AVM) as a nonsystemic pesticide possesses a low effective utilization rate. Studies of the multifunctional pesticide delivery system for improving biological activity are developing prosperously. In this study, multifunctional avermectin/polysuccinimide with glycine methyl ester nanoparticles (AVM-PGA) were prepared by the self-assembly process. The AVM loading capacity was up to 23.7%. After 24 h of UV irradiation, there was still about 70% of AVM remaining in PGA42 nanocarriers, as opposed to less than 5% of the free-form AVM. The rising ambient pH promoted the release of AVM using an in vitro releasing test, revealing a favorable pH-responsively controlled-release property. The mortality rate of Plutella xylostella with 2.5 µg/mL of AVM content of AVM-PGA42 was 96.3% after 48 h, while that of free AVM was only 51.5%. In addition, the AVM could be detected in stems and all leaves treated with AVM-PGA42 nanoparticles, whereas rare AVM was detected only in treated leaves for the free-form AVM, which achieved the transportation of nanocarriers carrying AVM in rice for the first time. Furthermore, the PGA nanoparticles performed a good growth promoting effect on rice. These results show that the AVM-PGA42 nanopesticides have a great potential application prospect to control the pest and improve the drug utilization efficiency on agriculture.

Serum miR-21 and miR-125b as markers predicting neoadjuvant chemotherapy response and prognosis in stage II/III breast cancer.

The predictive value of serum miRNAs (ser-miRNA) for the response to neoadjuvant chemotherapy (NCT) and the prognosis of breast cancer patients were investigated in the current study. The study included 118 stage II/III breast cancer patients and 30 healthy adult women. Peripheral blood was drawn from participants before the start (baseline [BL]), at the end of the second cycle (first evaluation during NCT [FEN]), and at the end of NCT (second evaluation during NCT [SEN]). The expression of ser-miRNAs was examined by quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and their association with chemotherapy response and prognosis was analyzed. MiR-19a, miR-21, miR-125b, miR-155, miR-205, and miR-373 were significantly up-regulated in the serum of breast cancer patients at BL, miR-451 was significantly down-regulated, and miR-122 was unchanged compared with the levels in healthy women. The expression of ser-miR-125b and the changes of ser-miR-21 expression during NCT were associated with chemotherapy response and disease-free survival (DFS). In chemotherapy responders, ser-miR-125b expression was lower than that of non-responders at BL, FEN, and SEN, and ser-miR-21 levels decreased from BL to FEN and from BL to SEN. Survival analysis showed that patients with lower ser-miR-125b expression at BL, FEN, and SEN had favorable DFS, and those with decreased ser-miR-21 expression from BL to FEN and from BL to SEN had better DFS. In conclusion, ser-miR-21 and ser-miR-125b were identified as novel, noninvasive predictive markers for NCT response and prognosis in breast cancer.

Changes of serum miR34a expression during neoadjuvant chemotherapy predict the treatment response and prognosis in stage II/III breast cancer.

OBJECTIVE: To investigate the predictive value of serum miR34a (ser-miR34a) expression for the neoadjuvant chemotherapy (NACT) response and prognosis in breast cancer patients. METHODS: This study included 86 diagnosed stage II/III breast cancer patients and 20 healthy volunteers. Peripheral blood from every participant was collected before the start, at the end of the second cycle, and at the end of NACT. The expression of ser-miR34a was examined by qRT-PCR and its association with the chemotherapy response and prognosis was analyzed. RESULTS: The expression of ser-miR34a in breast cancer patients before NACT was significant higher than that of healthy volunteers. During the NACT, the changes in ser-miR34a expression were significantly associated with treatment response and disease-free survival (DFS). In responding patients, ser-miR34a levels at the end of the second cycle and at the end of NACT were significantly lower than before NACT (P=0.016 and P=0.002, respectively), and in non-responding patients, the changes were insignificant. Survival analyses showed that the patients with decreased ser-miR34a expression from the end of the second cycle and the end of NACT to before NACT had improved DFS compared with that of the patients with increasing ser-miR34a expression (P<0.001 for both). Cox regression analyses showed that the changes of ser-miR34a expression were independent prognostic indicators. CONCLUSIONS: Ser-miR34a is a novel, noninvasive predictive marker for NACT response and prognosis in breast cancer patients.

Preparation, Characterization and Intracellular Imaging of 2,4-Dichlorophenoxyacetic Acid Conjugated Gold Nanorods.

Visualizing the biodistribution of pesticides inside living cells is great importance for enhancing targeting of pesticides. Here we reported for the first time that gold nanorods (Au NRs) with size of 39.4 nm x 11.3 nm could be used as a fluorescent tracer to examine the distribution of a typical herbicide, 2,4-dichlorophenoxyacetic acid (2,4-D), in tobacco bright yellow 2 (BY-2) cells. The nanostructures of hybrid materials were analyzed by using Raman spectra and X-ray photoelectron spectroscopy (XPS), including spectra assignments and electronic property. These data revealed 2,4-D has successfully conjugated MP-Au NRs according to Raman and XPS. The biodistribution of the conjugates inside BY-2 cells was directly examined at 12 and 24 h by the two-photon microscopy. The intensity of two-photon luminescence (TPL) inside cells demonstrated that the conjugates could be localized and excluded by BY-2 cells. Thus, this labeling approach opens up new avenues to the facile and efficient labeling of pesticides.

miR-892a regulated PPP2R2A expression and promoted cell proliferation of human colorectal cancer cells.

Colorectal cancer (CRC) is one of the most common malignancy cancers in the world. Aberrant microRNA expression is involved in human diseases including cancer. In the present study, we investigated the miR-892a's role in CRC cell proliferation. We found that miR-892a was frequently upregulated in human colorectal cancer tissues and cell lines compared with the matched tumor adjacent tissues and normal colonic cell line FHC. Overexpression of miR-892a promoted cell proliferation and colony formation of CRC. Bioinformatics analysis further revealed PPP2R2A was identified as a potential miR-892a. Overexpression of miR-892a-in SW480 cells reduced PPP2R2A protein expression. Subsequently, data from luciferase reporter assays showed that PPP2R2A 3'-untranslated region (3'-UTR) carried the directly binding site of miR-892a. Furthermore, siRNA-mediated silencing of PPP2R2A blocked the inhibitory effect of miR-892a-in on CRC cell growth. In sum, our data provided compelling evidence that overexpression of miR-892a may provide a selective growth promotion for CRC cells by direct suppression of PPP2R2A expression.