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When seismic waves illuminate the subsurface medium and propagate back to the surface geophones, they bring back attenuation information (in terms of quality factor [Formula: see text]) related to the subsurface viscoelastic features. Such information can be reflected by high-frequency component loss, phase change, and amplitude decay. We develop a novel method of common-transmission gather (CTG) to directly indicate the subsurface seismic attenuation features. The CTG is defined as a group of traces with a range of subsurface offsets that contain all the seismic signals transmitting the same subsurface location. We first focus the surface seismic data backward on one selected horizon, such as one reservoir seal, using the wave equation redatuming approach. This simulates a new data set that can be assumed to be acquired by setting many virtual sources on the selected horizon and the associated receivers on the surface. The CTG is generated by isolating all the seismic events passing through the targets after computing the transmitted arrivals from the redatumed source to the related surface receivers. Because the wavepaths corresponding to the CTG are all influenced by the targets below the selected horizon, we can compute frequency-dependent attributes, such as frequency spectrum ratio, to evaluate the attenuation feature of the targets. Numerical tests on synthetic and field data sets validate that the CTG can be used to directly indicate the seismic attenuation.

BackgroundBlood-test-based methods of distinguishing between acute aortic syndromes (AASs) and non-ST-elevation myocardial infarction (NSTEMI) during the troponin-blind period of MethodsData were retrospectively collected from 178 patients with AASs and 460 patients with NSTEMI within 3 h of onset. Differential risk factors related to AASs were identified by univariate and multivariate logistic regression analyses for patients with onset ResultsD-dimer, fibrinogen, and age were identified as differential risk factors for AASs with the onset of ConclusionTime-dependent quality of D-dimer should be considered for discriminating AASs from NSTEMI. Both nomogram models may have a clinical utility for evaluating the probability of AASs.

BackgroundA growing evidence suggests that immune cells play a significant role in the pathogenesis of hypertensive disorders of pregnancy (HDP).Over the past 20 years, several studies have been conducted on the role of immune cells in hypertensive disorders of pregnancy. This study used bibliometric analysis to assess research hotspots and future trends in studies on immune cells in hypertensive disorders of pregnancy.MethodsWe extracted all relevant literature on immune cells and hypertensive disorders of pregnancy from the Web of Science core collection for the period of 2001 to 2021. We used VOS Viewer, CiteSpace, R-bibliometrix and Python for bibliometric analysis.ResultsWe identified 2,388 records published in 593 journals by 9,886 authors from 2,174 universities/institutions in 91 countries/regions. The number of publications tended to increase over time, with the highest number of publications in 2021, up to 205. The USA was the country with the most publications. UNIVERSITY OF MISSISSIPPI was the most influential institution. Lamarca B, Romero R, and Saito S were the most prolific authors. Finally, three research hotspot clusters were identified based on keywords, which reflected the role of immune cells in the development of hypertensive disorders of pregnancy, the current research status,and predicted hot spots for future research.ConclusionsOur study systematically analyzed the role of immune cells in the pathogenesis of hypertensive disorders of pregnancy in the last 20 years. Our results indicated that immune cells, such as T cells, natural killer (NK) cells,and macrophages, and the cytokines released such as TNF-α, IFN-γ in the maternal circulation and at the maternal-fetal interface would influence the development of hypertensive disorders of pregnancy and we need further investigate the role of individual immune cells and translational studies to provide new therapeutic perspectives to mitigate adverse perinatal outcomes due to hypertensive disorders of pregnancy. In conclusion, bibliometric studies provide a general overview of immune cells in the study of hypertensive disorders of pregnancy.

Additional file 2. QoR-15 score.

Additional file 5: Table S3. Potential pathogens identified by paired ETA and BALF mNGS.

Additional file 1: Table S1. Conventional microbiological tests used in this study.

Additional file 4: Figure S2. Concordance analysis between mNGS and CMT method. For the double-positive subset, the results of the two methods were divided into completely matched, partial matched, and completely mismatched. Abbreviation: ETA, endotracheal aspirates; BALF, bronchoalveolar lavage fluid; mNGS, metagenomic next-generation sequencing; CMT, conventional microbiological tests.

In our previous study, target drug delivery and treatment of malignant tumors have been achieved by using platelets as carriers loading nano-chemotherapeutic agents (ND-DOX). However, drug release from ND-DOX-loaded platelets is dependent on negative platelet activation by tumor cells, whose activation is not significant enough for the resulting drug release to take an effective anti-tumor effect. Exploring strategies to proactively manipulate the controlled release of drug-laden platelets is imperative. The present study innovatively revealed that photodynamic action can activate platelets in a spatiotemporally controlled manner. Consequently, based on the previous study, platelets were used to load iron oxide-polyglycerol-doxorubicin-chlorin e6 composites (IO-PG-DOX-Ce6), wherein the laser-triggered drug release ability and anti-tumor capability were demonstrated. The findings suggested that IO-PG-DOX-Ce6 could be stably loaded by platelets in high volume without any decrease in viability. Importantly and interestingly, drug-loaded platelets were significantly activated by laser irradiation, characterized by intracellular ROS accumulation and up-regulation of CD62p. Additionally, scanning electron microscopy (SEM) and hydrated particle size results also showed a significant aggregation response of laser irradiated-drug-loaded platelets. Further transmission electron microscopy (TEM) measurements indicated that the activated platelets released extracellularly their cargo drug after laser exposure, which could be taken up by co-cultured tumor cells. Finally, the co-culture model of drug-loaded platelets and tumor cells proved that laser-triggered delivery system of platelets could effectively damage the DNA and promote apoptosis of tumor cells. Overall, the present study discovers a drug-loaded platelets delivery using photodynamic effect, enabling laser-controlled intelligent drug delivery and anti-tumor therapy, which provides a novel and feasible approach for clinical application of cytopharmaceuticals. What is the context? 1. Platelets were applied to load IO-PG-DOX-Ce6, wherein the laser-triggered drug release and anti-tumor effect were investigated in vitro. 2. The findings indicated that IO-PG-DOX-Ce6 could be stably loaded by platelets in high volume without any decrease in viability, which may attribute to the activation of autophagy in platelets. 3. IO-PG-DOX-Ce6-loaded platelets could be significantly activated by laser irradiation (690 nm). 4. Activated platelets released extracellularly their cargo drug after laser exposure, which could be taken up by co-cultured tumor cells 5. The co-culture model of drug-loaded platelets and tumor cells proved that the laser-triggered delivery system of platelets could effectively damage the DNA and promote apoptosis of tumor cells. What is new? 1. Platelets could be utilized as the vehicle to load photosensitizer-loaded-nano-drug. 2. Photodynamic action can activate platelets in a spatiotemporally controlled manner, which could be a tool to regulate the activation of platelets. 3. The laser-triggered activation of drug-loaded platelets allows for target release of cargo. 4. The limitation of the current research is that only in vitro experiments were carried out to demonstrate our conclusions. What is impact? The present work provides a novel and feasible approach for the clinical application of cytopharmaceuticals.

Additional file 2: Table S2. The protocols and primers of real-time quantitative PCR for detecting 17 pathogens.

Additional file 1. Preoperative, intraoperative and postoperative CRFs.

Additional file 3: Figure S1. The overlap of positivity between mNGS technique and CMT for different pathogens. The pathogens were observed to have a higher positive rate by mNGS than that by CMT, and the difference was significant. Abbreviation: ETA, endotracheal aspirates; BALF, bronchoalveolar lavage fluid; mNGS, metagenomic next-generation sequencing; CMT, conventional microbiological tests.

Additional file 3. Informed consent form.

In this paper, a novel nonlinear precoding (NLP) technique, namely constellation-oriented perturbation (COP), is proposed to tackle the scalability problem inherent in conventional NLP techniques. The basic concept of COP is to apply vector perturbation (VP) in the constellation domain instead of symbol domain; as often used in conventional techniques. By this means, the computational complexity of COP is made independent to the size of multi-antenna (i.e., MIMO) networks. Instead, it is related to the size of symbol constellation. Through widely linear transform, it is shown that COP has its complexity flexibly scalable in the constellation domain to achieve a good complexity-performance tradeoff. Our computer simulations show that COP can offer very comparable performance with the optimum VP in small MIMO systems. Moreover, it significantly outperforms current sub-optimum VP approaches (such as degree-2 VP) in large MIMO whilst maintaining much lower computational complexity., Comment: 6 pages, 6 figures, published on the conference of GLOBECOM2022

As the overuse of nitrogen fertilizer has caused series of environmental problems, improving the nitrogen use efficiency of rice crop has been drawing much attention. Since developing nitrogen-efficient rice genotypes is a feasible solution, illustrating the microbiological characteristics of the nitrogen-efficient rice genotypes is of great importance. We performed a field experiment, and planted 16 genotypes of rice. The nitrogen utilization efficiencies and yields of rice were examined. Real-time PCR and Illumina sequencing were employed to investigate the abundance of the nitrogen-cycle related genes and the bacterial community structure of the rhizosphere. The results revealed that rice genotypes enriched specific bacterial communities to inhabit in the rhizosphere at both the taxonomic and functional levels. The enriched bacteria were mainly involved in the functions of nitrogen transformation, ferric iron reduction, organic compound biodegradation, and sulfur transformation. We observed a strong correlation between the yield and the abundance of rhizospheric functional bacteria, especially the groups of Proteobacteria and Chloroflexi. The analysis of nitrite reductase and denitrifying genes showed that the denitrification activity in the rhizosphere inversely correlate with the efficiency of nitrogen utilization. We reason that a smaller denitrifying bacteria population leads to less the nitrogen loss in the rhizosphere, thus an increase of available nitrogen and a higher rice yield. This research revealed how functional bacteria assembled in the rhizosphere of rice genotypes with varied nitrogen use efficiencies, which may provide valuable information with regard to the improvement of nitrogen use efficiency and reduction of fertilizer application.

In this study, a simple pH-colorimetric film was developed to detect the spoilage of pasteurized milk. The biosensor was fabricated by incorporating the pH-sensitive anthocyanins (AC) extracted from blue pea (Clitoria ternatea L.) flower into a starch-based edible film. The color responses of both AC aqueous extracts and edible films incorporated with different AC concentrations towards different pH buffers (pH 2–11) were measured using Ultraviolet–visible (UV–Vis) spectrophotometer and colorimeter, respectively. Based on the results, there were significant differences (p

Background The side effects of chemotherapy-induced nausea and vomiting (CINV) and myelosuppression reduce the cancer patients’ adherence to chemotherapy. Many Chinese patients choose Chinese medicine (CM) during chemotherapy to reduce side effects; however, the evidence is lacking. The efficacy of a CM herbal treatment protocol, Jianpi Bushen Sequential Formula (健脾补肾续贯方, JBSF) will be evaluated on chemotherapy completion rate among patients with colon cancer. Methods A multi-center double-blind randomized controlled trial (RCT) will be conducted on 400 patients with colon cancer who will receive 8 cycles of adjuvant chemotherapy with oxaliplatin and capecitabine (CAPEOX). Patients will be randomized 1:1 to receive the JBSF or placebo formula. The primary outcome is the overall chemotherapy completion rate. The secondary outcomes include individual chemotherapy completion rate, 4-cycle completion rate of chemotherapy, time to treatment failure, relative dose intensity and treatment toxicity. Follow-up visits will be scheduled before every and after last chemotherapy. Discussion This study will provide evidence on whether JBSF can improve the chemotherapy completion rate and reduce side effects among patients with colon cancer. (Trial registration: ClinicalTrials.gov, No. NCT03716518)

Chlorin e6 (Ce6) is a promising photosensitizer for tumor photodynamic therapy (PDT). However, the efficacy of Ce6 PDT is limited by Ce6's poor water solubility, rapid blood clearance, and inadequate accumulation in the tumor tissue. This problem is tackled in this work, wherein functionalized superparamagnetic iron oxide nanoparticles (IO-NPs) were used as carriers to deliver Ce6 to melanoma. The IO-NPs were coated with polyglycerol (PG) to afford good aqueous solubility. The chemotherapeutic agent doxorubicin (DOX) was attached to the PG coating via the hydrazone bond to afford affinity to the cell membrane and thereby promote the cell uptake. The hydrophobic nature of DOX also induced the aggregation of IO-NPs to form nanoclusters. Ce6 was then loaded onto the IO nanoclusters through physical adsorption and coordination with surface iron atoms, yielding the final composites IO-PG-DOX-Ce6. In vitro experiments showed that IO-PG-DOX-Ce6 markedly increased Ce6 uptake in mouse melanoma cells, leading to much-enhanced photocytotoxicity characterized by intensified reactive oxygen species production, loss of viability, DNA damage, and stimulation of tumor cell immunogenicity. In vivo experiments corroborated the in vitro findings and demonstrated prolonged blood clearance of IO-PG-DOX-Ce6. Importantly, IO-PG-DOX-Ce6 markedly increased the Ce6 distribution and retention in mouse subcutaneous melanoma grafts and significantly improved the efficacy of Ce6-mediated PDT. No apparent vital organ damage was observed at the same time. In conclusion, the IO-PG-DOX NPs provide a simple and safe delivery platform for efficient tumor enrichment of Ce6, thereby enhancing antimelanoma PDT.

Lung cancer recruits tumor-associated macrophages (TAMs) massively, whose predominantly pro-tumor M2 phenotype leads to immunosuppression. Dihydroartemisinin (DHA) has been proven to remodel TAM into an anti-tumor M1 phenotype at certain concentrations in the present study, which was hypothesized to facilitate anti-lung cancer immunotherapy. However, how DHA remodels the TAM phenotype has not yet been uncovered. Our previous work revealed that DHA could trigger ferroptosis in lung cancer cells, which may also be observed in TAM thereupon. Sequentially, in the current study, DHA was found to remodel TAM into the M1 phenotype in vitro and in vivo. Simultaneously, DHA was observed to trigger ferroptosis in TAM and cause the DNA damage response and NF-κB activation. Conversely, the DHA-induced DNA damage response and NF-κB activation in TAM were attenuated after the inhibition of ferroptosis in TAM using an inhibitor of ferroptosis. Importantly, a ferroptosis inhibitor could also abolish the DHA-induced phenotypic remodeling of TAM toward the M1 phenotype. In a nutshell, this work demonstrates that DHA-triggered ferroptosis of TAM results in DNA damage, which could activate downstream NF-κB to remodel TAM into an M1 phenotype, providing a novel strategy for anti-lung cancer immunotherapy. This study offers a novel strategy and theoretical basis for the use of traditional Chinese medicine monomers to regulate the anti-tumor immune response, as well as a new therapeutic target for TAM phenotype remodeling.

With the expert consensus during the clinical questions determination in the World Federation of Acupuncture and Moxibustion Societies (WFAS) standard以世界针灸学会联合会（WFAS）标准《女性尿失禁针灸临床实践指南》临床问题确定的专家共识为例，围绕指南研制组专家三轮德尔菲法调研临床问题的具体过程及结果，系统分析改良德尔菲法与针灸类专家共识的契合度以及本次共识过程的反思与不足，以期为同领域针灸指南的研制提供参考。.

Background: Shufeng Jiedu (SFJD) capsules can be used as adjunctive treatment for patients with community-acquired pneumonia, but the effectiveness and safety of SFJD are not clear. This review aims to evaluate the effectiveness and safety of SFJD based on randomized controlled trials (RCTs).Methods: A systematic review was conducted by searching PubMed, Embase, Scopus, Web of Science, CENTRAL, CNKI, VIP, CBM, Wanfang and trial registry platforms from their inception to March 2022. Two reviewers screened studies, extracted the data and assessed risk of bias independently. The data were pooled for meta-analysis or presented narratively.Results: Seventeen RCTs involving 1840 participants were included. All trials compared SFJD plus antibiotics to antibiotics, or combined with symptomatic treatment in both groups. The overall certainty of evidence was assessed as moderate to very low certainty. Compared with routine treatment (antibiotics alone or antibiotics plus symptomatic treatment), SFJD plus routine treatment showed beneficial effects in resolution of fever (MD −1.20 days, 95%CI −1.73 to −0.67; 10 RCTs; very low certainty), cough (MD −1.02 days, 95%CI −1.23 to −0.81; 9 RCTs; moderate certainty), phlegm (MD −1.46 days, 95%CI −2.84 to −0.08; 6 RCTs; very low certainty), pulmonary crepitations (MD −1.61 days, 95%CI −2.64 to −0.59; 8 RCTs; low certainty), shortness of breath (MD −2.80 days, 95%CI −2.88 to −2.72; 2 RCTs; low certainty) and chest pain (MD −2.85 days, 95%CI −3.01 to −2.69; 1 RCT; low certainty). There was no significant difference in pathogen clearance (1 RCT). No serious adverse events were reported, but 2.60% (5/192) patients reported nausea in the SFJD groups, 1.04% (2/192) participants in routine group, and no significant difference was identified.Conclusions: Current evidence suggests that adding SFJD may shorten the duration of symptom relief in community-acquired pneumonia for 1–2 days. The adverse events were minor and controllable, and no serious adverse events were reported. Well-reported trials and potential of reducing antibiotics were expected in the future studies.

BackgroundHeart failure (HF) is associated with generalized insulin resistance (IR). Recent studies demonstrated that triglyceride glucose (TyG) is an effective alternative index of IR. However, the relationship between the TyG index and in-hospital mortality in patients with HF is unclear. In the present study, we aimed to clarify the association between the TyG index and in-hospital mortality in patients with HF.MethodsA retrospective study consisting of 4,411 patients diagnosed with HF from 2015 to 2018 was conducted. All-cause mortality during hospitalization was the primary endpoint. The association between the TyG index and in-hospital mortality was assessed using the logistic regression analysis.ResultsThe risk of in-hospital mortality was significantly associated with increased TyG index (OR: 1.886, 95% CI: 1.421–2.501, p < 0.001) under logistic regression with multivariable adjustment. When divided into three groups based on the TyG index, Tertile 3 demonstrated significantly higher in-hospital mortality than the other two Tertiles (OR: 2.076, 95% CI: 1.284–3.354, p = 0.001). Moreover, the TyG index improved the prediction efficiency of the Get with the Guidelines-Heart Failure (GWTG-HF) score (absolute integrated discrimination improvement = 0.006, p < 0.001; category-free net reclassification improvement = 0.075, p = 0.005). In subgroup analysis, the TyG index exhibited similar predictive performance of in-hospital mortality when groups were stratified based on type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD).ConclusionTyG is a potential index for predicting in-hospital mortality in patients with HF, independent of T2DM or CAD status. The TyG index may be combined with the GWTG-HF score to further improve its predictive efficacy.

Astrocytes are key stromal components in glioblastoma (GBM) and have complex interactions with the GBM cells (GBC) promoting the survival, progression and therapy resistance of GBM. In this study, we first demonstrated the existence of a reciprocal activation loop mediated by the STAT3/IL-6 signaling between GBC and astrocytes. This loop of reciprocity was found to be initiated by the constitutive activity of STAT3 and downstream expression of IL-6 in the GBC. GBC-derived IL-6 activated STAT3 and thereby upregulated IL-6 expression in the astrocytes. Astrocyte-derived IL-6 acted back on the GBC causing further activation of STAT3 and leading to enhanced downstream events that promote proliferation, migration, invasion and apoptosis resistance of the GBC. Next, we showed that doxorubicin-polyglycerol-nanodiamond conjugates (Nano-DOX), which could be delivered via GBM-associated macrophages, suppressed STAT3 activity in the GBC reducing their IL-6 output to the astrocytes and thereby abolished the astrocytes' feedback activation of the GBC. Moreover, Nano-DOX also suppressed stimulated activation of STAT3 and IL-6 induced by temozolomide, a first-line anti-GBM chemotherapy, resistance to which critically involves STAT3 activation. In conclusion, Nano-DOX could disrupt the STAT3/IL-6-mediated reciprocal activation loop between the GBC and astrocytes. Nano-DOX also provides a novel approach to therapeutic modulation of the GBM microenvironment.

The present study showed that pretreatment of triadimefon (TDM), a triazole compound, could improve tolerance of soybean seedlings to subsequent water stress. TDM pretreatment resulted in early and late rise in superoxide dismutase (SOD) and catalase (CAT) activities, and upregulation of ascorbate (AsA) content in non-stressed and water-stressed seedlings, leading to late increase in net photosynthetic rate (Pn), late decrease in hydrogen peroxide (H2O2) and electrolyte leakage in stressed ones. These TDM-induced changes were blocked by application of abscisic acid (ABA) biosynthesis inhibitor tungstate, which inhibited early rise of ABA and H2O2 contents in non-stressed and stressed seedlings. However, ABA pretreatment overcomed the effects of this inhibitor. Application of NADPH oxidase inhibitor diphenyleneiodonium (DPI), polyamine oxidase (PAO) inhibitor 2-hydroxyethylhydrazine (2-HEH) and H2O2 scavenger dimethylthiourea (DMTU) prevented early TDM-induced rise of H2O2 content. DPI, 2-HEH and DMTU also decreased SOD, CAT and AsA levels, but did not affect ABA content during early and late phases in both seedlings pretreated with TDM. In addition, these chemicals decreased Pn, and increased H2O2 content and electrolyte leakage during late phase in TDM-pretreated stressed seedlings. Overall, these results indicated that TDM pretreatment alleviated adverse effects of water stress on soybean seedlings, which was at least in part, due to increase of antioxidant capacity and decrease of oxidative damage induced by early ABA-dependent H2O2 generation.

In recent years, the real-world studies (RWS) have attracted extensive attention, and the real-world evidence (RWE) has been accepted to support the drug development in China and abroad. However, there is still a lack of standards for the evaluation of the quality of RWE. It is necessary to formulate a quality evaluation and reporting specification for RWE especially in traditional Chinese medicine (TCM). To this end, under the guidance of China Association of Chinese Medicine, the Quality Evaluation and Reporting Specification for Real-World Evidence of Traditional Chinese Medicine (QUERST) Group, including 24 experts (clinical epidemiologists, clinicians, pharmacologists, ethical reviewer and statisticians), was established to develop the specification. This specification contains the listing of classification of RWS design and RWE, the general principles and methods of RWE quality evaluation (26 tools or scales), 25 types of bias in RWS, the special considerations in evaluating the quality of RWE of TCM, and the 19 reporting standards of RWE. This specification aims to propose the quality evaluation principles and key points of RWE, and provide guidance for the proper use of RWE in the development of TCM new drugs.

Lung cancer recruits tumor-associated macrophages (TAMs) massively, whose predominantly pro-tumor M2 phenotype leads to immunosuppression. Dihydroartemisinin (DHA) has been proven to remodel TAM into an anti-tumor M1 phenotype at certain concentrations in the present study, which was hypothesized to facilitate anti-lung cancer immunotherapy. However, how DHA remodels the TAM phenotype has not yet been uncovered. Our previous work revealed that DHA could trigger ferroptosis in lung cancer cells, which may also be observed in TAM thereupon. Sequentially, in the current study, DHA was found to remodel TAM into the M1 phenotype

Background Chemodynamic therapy (CDT) relying on intracellular iron ions and H2O2 is a promising therapeutic strategy due to its tumor selectivity, which is limited by the not enough metal ions or H2O2 supply of tumor microenvironment. Herein, we presented an efficient CDT strategy based on Chinese herbal monomer-dihydroartemisinin (DHA) as a substitute for the H2O2 and recruiter of iron ions to amplify greatly the reactive oxygen species (ROS) generation for synergetic CDT-ferroptosis therapy. Results The DHA@MIL-101 nanoreactor was prepared and characterized firstly. This nanoreactor degraded under the acid tumor microenvironment, thereby releasing DHA and iron ions. Subsequent experiments demonstrated DHA@MIL-101 significantly increased intracellular iron ions through collapsed nanoreactor and recruitment effect of DHA, further generating ROS thereupon. Meanwhile, ROS production introduced ferroptosis by depleting glutathione (GSH), inactivating glutathione peroxidase 4 (GPX4), leading to lipid peroxide (LPO) accumulation. Furthermore, DHA also acted as an efficient ferroptosis molecular amplifier by direct inhibiting GPX4. The resulting ROS and LPO caused DNA and mitochondria damage to induce apoptosis of malignant cells. Finally, in vivo outcomes evidenced that DHA@MIL-101 nanoreactor exhibited prominent anti-cancer efficacy with minimal systemic toxicity. Conclusion In summary, DHA@MIL-101 nanoreactor boosts CDT and ferroptosis for synergistic cancer therapy by molecular amplifier DHA. This work provides a novel and effective approach for synergistic CDT-ferroptosis with Chinese herbal monomer-DHA and Nanomedicine. Graphical Abstract

In order to cope with the increasingly severe air defense threat and the problem of low cost-effectiveness ratio of traditional air defense missiles, this paper presents an overall scheme of smart floating munition, a small air defense weapon featuring low cost and high cost-effectiveness ratio, which can be used in batches. The composition and working principle of this weapon system are introduced, and the main technologies involved and solutions are discussed in detail. It can be used as a weapon supplement for Chinese military’s specific airspace blockade in the future.

Objective A systematic review of animal and human studies was conducted on genetically modified (GM) food consumption to assess its safety in terms of adverse effects/events to inform public concerns and future research. Methods Seven electronic databases were searched from January 1st 1983 till July 11th 2020 for in vivo, animal and human studies on the incidence of adverse effects/events of GM products consumption. Two authors independently identified eligible studies, assessed the study quality, and extracted data on the name of the periodical, author and affiliation, literature type, the theme of the study, publication year, funding, sample size, target population characteristics, type of the intervention/exposure, outcomes and outcome measures, and details of adverse effects/events. We used the Chi-square test to compare the adverse event reporting rates in articles funded by industry funding, government funding or unfunded articles. Results One crossover trial in humans and 203 animal studies from 179 articles met the inclusion criteria. The study quality was all assessed as being unclear or having a high risk of bias. Minor illnesses were reported in the human trial. Among the 204 studies, 59.46% of adverse events (22 of 37) were serious adverse events from 16 animal studies (7.84%). No significant differences were found in the adverse event reporting rates either between industry and government funding (χ2 = 2.286, P = 0.131), industry and non-industry funding (χ2 = 1.761, P = 0.185) or funded and non-funded articles (χ2 = 0.491, P = 0.483). We finally identified 21 GM food-related adverse events involving 7 GM events (NK603 × MON810 maize, GTS 40-3-2 soybean, NK603 maize, MON863 maize, MON810 maize, MON863 × MON810 × NK603 maize and GM Shanyou 63 rice), which had all been on regulatory approval in some countries/regions. Conclusion Serious adverse events of GM consumption include mortality, tumour or cancer, significant low fertility, decreased learning and reaction abilities, and some organ abnormalities. Further clinical trials and long-term cohort studies in human populations, especially on GM food-related adverse events and the corresponding GM events, are still warranted. It suggests the necessity of labelling GM food so that consumers can make their own choice.

Additional file 1. Protocol and Statistical Analysis Plan.

Additional file 2. Table S1. Feeding intolerance score. Table S2. Recruitment of patients. Table S3. Proportion of patients receiving enteral and/or parenteral nutrition. Table S4. Proportion of patients receiving enteral nutrition. Table S5. Proportion of patients receiving parenteral nutrition. Table S6. Proportion of enteral nutrition delivered energy in daily energy delivery. Table S7. Target-reaching rate in fed patients from day1 to day7 after enrollment. Table S8. Protein intake from day1 to day7 after enrollment. Table S9. Organ failure-related outcomes. Figure S1. Proportion of enteral nutrition delivered energy in daily energy delivery within the first seven days after enrollment. Figure S2. Target-reaching (more than 70% of the estimated energy target) rate in fed patients for energy delivery from day1 to day7 after enrollment. Figure S3. Daily protein intake from day1 to day7 after enrollment.

Additional file 3. Continued Table 1. Baseline ICU and Patient-Level Characteristics..

Supplemental material, sj-docx-1-npx-10.1177_1934578X221125056 for Cytotoxic Biflavonoids from Selaginella braunii by Xue-Feng Liu, Tong-Fei Fu, Jun-Song Wu, Bi-Chao Lu, Ping Zhang and He-Jing Liu in Natural Product Communications

Additional file 1: Figure S1. Size distribution of MIL-101-NH2, hydrodynamic diameters and stability evaluation of DHA@MIL-101. Figure S2. UV–vis absorption spectra of DHA, MIL-101-NH2 and DHA@MIL-101-NH2. Figure S3. TGA curves of MIL-101-NH2 and DHA@MIL-101-NH2. Figure S4. SEM images of ICN-DHA@MIL-101. Figure S5. UV–vis absorption spectra of ICG and ICG-DHA@MIL-101-NH2. Figure S6 Uptake of ICG-DHA@MIL-101 in LLC. Figure S7. DHA up-regulated the expression of TfR1 in LLC. Figure S8. DHA@MIL-101 promoted Nuclear translocation of NF-κB of LLC. Figure S9. DHA@MIL-101 promoted phosphorylation of NF-κB of LLC. Figure S10. The ICG-DHA@MIL-101 distribution in tumor grafts. Figure S11. The COX-2 and γ-H2A.X expression in tumor grafts. Figure S12. DHA@MIL-101 induced prominent apoptosis and necrosis of cancer cells in tumor grafts. Figure S13. DHA@MIL-101 promoted the expression of Bax, caspase-3, decreased expression of PCNA in tumor grafts. Figure S14. The body weight of LLC-bearing mice varied little after DHA@MIL-101 treatment. Figure S15. No evident organ toxicity in DHA@MIL-101-treated mice. Figure S16. LPO in LLC was detected using C11-BODIPY probe with confocal microscopy. Figure S17. Quantitative gray analysis of WB results in Fig. 2 to Fig. 4.

Additional file 1.

Additional file 2.

The present work aims to prove the concept of tumor-targeted drug delivery mediated by platelets. Doxorubicin (DOX) attached to nanodiamonds (ND-DOX) was investigated as the model payload drug of platelets. In vitro experiments first showed that ND-DOX could be loaded in mouse platelets in a dose-dependent manner with a markedly higher efficiency and capacity than free DOX. ND-DOX-loaded platelets (Plt@ND-DOX) maintained viability and ND-DOX could be stably held in the platelets for at least 4 hr. Next, mouse Lewis lung cancer cells were found to activate Plt@ND-DOX and thereby stimulate cargo unloading of Plt@ND-DOX. The unloaded ND-DOX was taken up by co-cultured cancer cells which consequently exhibited loss of viability, proliferation suppression and apoptosis. In vivo, Plt@ND-DOX displayed significantly prolonged blood circulation time over ND-DOX and DOX in mice, and Lewis tumor grafts demonstrated infiltration, activation and cargo unloading of Plt@ND-DOX in the tumor tissue. Consequently, Plt@ND-DOX effectively reversed the growth of Lewis tumor grafts which exhibited significant inhibition of cell proliferation and apoptosis. Importantly, Plt@ND-DOX displayed a markedly higher therapeutic potency than free DOX but without the severe systemic toxicity associated with DOX. Our findings are concrete proof of platelets as efficient and efficacious carriers for tumor-targeted nano-drug delivery with the following features: 1) large loading capacity and high loading efficiency, 2) good tolerance of cargo drug, 3) stable cargo retention and no cargo unloading in the absence of stimulation, 4) prolonged blood circulation time, and 5) excellent tumor distribution and tumor-activated drug unloading leading to high therapeutic potency and few adverse effects. Platelets hold great potential as efficient and efficacious carriers for tumor-targeted nano-drug delivery.

The tumor-associated macrophage (TAM) serves as an immunosuppressive agent in the malignant tumor microenvironment, facilitating the development and metastasis of lung cancer. The photodynamic effect destabilizes cellular homeostasis owing to the generation of reactive oxygen species (ROS), resulting in the enhanced pro-inflammatory function of immunocytes. In our previous study, the Ce6-mediated photodynamic effect was found to have kept the viability of macrophages and to remodel them into the M1 phenotype. However, the mechanism remains unrevealed. The present study now explores the mechanism of photodynamic therapy (PDT)-mediated reprogramming of macrophages. As expected, Ce6-mediated PDT was capable of generating reactive oxygen species, which was continuously degraded, causing “low intensity” damage to DNA and thereby triggering subsequent DNA damage response in macrophages. The autophagy was thus observed in Ce6-treated macrophages and was shown to protect cells from being photodynamically apoptotic. More importantly, Ce6 PDT could activate the stimulator of interferon genes (STING) molecule, a sensor of DNA damage, which could activate the downstream nuclear factor kappa-B (NF-κB) upon activation, mediating the polarization of macrophages towards the M1 phenotype thereupon. In addition, inhibition of ROS induced by PDT attenuated the DNA damage, STING activation, and M1-phenotype reprogramming. Furthermore, the silence of the STING weakened Ce6 treatment-mediated M1 remodeling of macrophages as well. Altogether, these findings indicate the Ce6-induced photodynamic effect polarizes macrophages into an M1 phenotype through oxidative DNA damage and subsequent activation of the STING. This work reveals the crucial mechanism by which photodynamic therapy regulates the macrophage phenotype and also provides a novel intervenable signaling target for remodeling macrophages into the M1 phenotype.

Photodynamic therapy (PDT) is noninvasive, low toxicity, and photo-selective, but may be resisted by malignant cells. A previous study found chlorin e6 (Ce6) mediated PDT showed drug resistance in lung cancer cells (LLC), which may be associated with PDT-induced DNA damage response (DDR). DDR may up-regulate glutathione peroxidase 4 (GPX4), which in turn degrade ROS induced by PDT. However, dihydroartemisinin (DHA) was found to down-regulate GPX4. Accordingly, the DHA was hypothesized to improve the resistance to PDT. The present work explores the mechanism of Ce6 mediated drug resistance and reveals whether DHA can enhance the efficacy of PDT by suppressing GPX4. The in vitro experiments found Ce6 treatment did not inhibit the viability of LLC within 6 h without inducing significant apoptosis, suggesting LLC were resistant to PDT. Further investigation demonstrated PDT could damage DNA and up-regulate GPX4, thus degrading the generated ROS. DHA effectively inhibited the viability of LLC and induced apoptosis. Importantly, DHA displayed a prominent inhibitory effect on the GPX4 expression and thereby triggered ferroptosis. Combining DHA with Ce6 for treatment of LLC resulted in the suppressed GPX4 and elevated ROS. Finally, the findings showed DHA combined with Ce6 exhibited superb anti-lung cancer efficacy. In summary, Ce6 PDT damages DNA, up-regulates GPX4 to degrade ROS, thereby inducing drug resistance. Down-regulation of GPX4 by DHA-triggered ferroptosis significantly enhances the efficacy of PDT. This study provides an outstanding theoretical basis for the regulation of the intratumoral redox system and improving PDT efficacy against lung cancer by herbal monomer DHA.

Suppression of the immune microenvironment is an important endogenous contributor to treatment failure in lung cancer. Photodynamic therapy (PDT) is widely used in the treatment of malignant tumors owing to its photo-selectivity and minimal side effects. Some studies have shown the ability of photodynamic action not only to cause photo-cytotoxicity to tumor cells but also to induce immunogenic cell death (ICD). However, the mechanism by which PDT enhances tumor immunogenicity is poorly understood. The present study aimed to explore the immunogenicity effect of PDT on lung cancer and to reveal the underlying mechanism. First, we searched for effective conditions for PDT-induced apoptosis in lung cancer cells. Just as expected, chlorin e6 (Ce6) PDT could enhance the immunogenicity of lung cancer cells alongside the induction of apoptosis, characterized by up-regulation of CRT, HSP90, HMGB1 and MHC-I. Further results showed the generation of ROS by Ce6 PDT under the above conditions, which is an oxidative damaging agent. Simultaneously, PDT induced endoplasmic reticulum (ER) stress in cells, as evidenced by enhanced Tht staining and up-regulated CHOP and GRP78 expression. Moreover, PDT led to DNA damage response (DDR) as well. However, the redox inhibitor NAC abolished the ER stress and DDR caused by PDT. More importantly, NAC also attenuated PDT-induced improvement of immunogenicity in lung cancer. On this basis, the PDT-induced CRT up-regulation was found to be attenuated in response to inhibition of ER stress. In addition, PDT-induced increase in HMGB1 and HSP90 release was blocked by inhibition of DDR. In summary, Ce6 PDT could produce ROS under certain conditions, which leads to ER stress that promotes CRT translocation to the cell membrane, and the resulting DNA damage causes the expression and release of nuclear HMGB1 and HSP90, thereby enhancing the immunogenicity of lung cancer. This current study elucidates the mechanism of PDT in ameliorating the immunogenicity of lung cancer, providing a rationale for PDT in regulating the immune microenvironment for the treatment of malignant tumors.