Albumin-encapsulated HSP90-PROTAC BP3 nanoparticles not only retain protein degradation ability but also enhance the antitumour activity of BP3 in vivo.

Proteolysis-targeting chimaera (PROTAC) has received extensive attention in industry. However, there are still some limitations that hinder its further development. In a previous study, our group first demonstrated that the HSP90 degrader BP3 synthesised by the principle of PROTACs showed therapeutic potential for cancer. However, its application was hindered by its high molecular weight and water insolubility. Herein, we aimed to improve these properties of HSP90-PROTAC BP3 by encapsulating it into human serum albumin nanoparticles (BP3@HSA NPs). The results demonstrated that BP3@HSA NPs showed a uniform spherical shape with a size of 141.01 ± 1.07 nm and polydispersity index < 0.2; moreover, BP3@HSA NPs were more readily taken up by breast cancer cells and had a stronger inhibitory effect in vitro than free BP3. BP3@HSA NPs also demonstrated the ability to degrade HSP90. Mechanistically, the improved inhibitory effect of BP3@HSA NPs on breast cancer cells was related to its stronger ability to induce cell cycle arrest and apoptosis. Furthermore, BP3@HSA NPs improved PK properties and showed stronger tumour suppression in mice. Taken together, this study demonstrated that hydrophobic HSP90-PROTAC BP3 nanoparticles encapsulated by human serum albumin could improve the safety and antitumour efficacy of BP3.

CT-guided microcoil localization for scapula-blocked pulmonary nodules using penetrating lung puncture before video-assisted thoracic surgery.

PURPOSE: To retrospectively analyze the effectiveness and safety of computed tomography (CT)-guided microcoil localization for scapula-blocked pulmonary nodules using penetrating lung puncture prior to video-assisted thoracic surgery (VATS). METHODS: One hundred thirty-eight patients with 138 pulmonary nodules were included in this single-center retrospective study. Among them, 110 patients who underwent CT-guided microcoil localization using the routine puncture technique formed the routine group; the other 28 patients who underwent the CT-guided microcoil localization using the penetrating lung puncture technique formed the penetrating lung group. The main outcomes were the success rate and complication rate of the two groups. RESULTS: The localization success rate was 95.5% (105/110) in the routine group and 89.3% (25/28) in the penetrating lung group (P = 0.205). There was no statistical difference in any of the complications (pneumothorax, intrapulmonary hemorrhage, or moderate and severe chest pain) in both groups (P = 0.178, P = 0.204, P = 0.709, respectively). Localization procedure time was significantly increased in the penetrating lung group compared with the routine group (31.0 ± 3.0 min vs. 21.2 ± 2.8 min, P < 0.001). CONCLUSION: CT-guided microcoil localization for scapula-blocked pulmonary nodules using penetrating lung puncture prior to VATS resection is effective and safe. However, the deployment of the microcoil using penetrating lung puncture required more time than the routine puncture method.

Floquet Engineering of Nonequilibrium Valley-Polarized Quantum Anomalous Hall Effect with Tunable Chern Number.

Here, we propose that Floquet engineering offers a strategy to realize the nonequilibrium quantum anomalous Hall effect (QAHE) with tunable Chern number. Using first-principles calculations and Floquet theorem, we unveil that QAHE related to valley polarization (VP-QAHE) is formed from the hybridization of Floquet sidebands in the two-dimensional family MSi2Z4 (M = Mo, W, V; Z = N, P, As) by irradiating circularly polarized light (CPL). Through the tuning of frequency, intensity, and handedness of CPL, the Chern number of VP-QAHE is highly tunable and up to C = ±4, which attributes to light-induced trigonal warping and multiple-band inversion at different valleys. The chiral edge states and quantized plateau of Hall conductance are visible inside the global band gap, thereby facilitating the experimental measurement. Our work not only establishes Floquet engineering of nonequilibrium VP-QAHE with tunable Chern number in realistic materials but also provides an avenue to explore emergent topological phases under light irradiation.

NDFIP1 limits cellular TAZ accumulation via exosomal sorting to inhibit NSCLC proliferation.

NDFIP1 has been previously reported as a tumor suppressor in multiple solid tumors, but the function of NDFIP1 in NSCLC and the underlying mechanism are still unknown. Besides, the WW domain containing proteins can be recognized by NDFIP1, resulted in the loading of the target proteins into exosomes. However, whether WW domain-containing transcription regulator 1 (WWTR1, also known as TAZ) can be packaged into exosomes by NDFIP1 and if so, whether the release of this oncogenic protein via exosomes has an effect on tumor development has not been investigated to any extent. Here, we first found that NDFIP1 was low expressed in NSCLC samples and cell lines, which is associated with shorter OS. Then, we confirmed the interaction between TAZ and NDFIP1, and the existence of TAZ in exosomes, which requires NDFIP1. Critically, knockout of NDFIP1 led to TAZ accumulation with no change in its mRNA level and degradation rate. And the cellular TAZ level could be altered by exosome secretion. Furthermore, NDFIP1 inhibited proliferation in vitro and in vivo, and silencing TAZ eliminated the increase of proliferation caused by NDFIP1 knockout. Moreover, TAZ was negatively correlated with NDFIP1 in subcutaneous xenograft model and clinical samples, and the serum exosomal TAZ level was lower in NSCLC patients. In summary, our data uncover a new tumor suppressor, NDFIP1 in NSCLC, and a new exosome-related regulatory mechanism of TAZ.

Enhanced Nanobubble Formation: Gold Nanoparticle Conjugation to Qß Virus-like Particles.

Plasmonic gold nanostructures are a prevalent tool in modern hypersensitive analytical techniques such as photoablation, bioimaging, and biosensing. Recent studies have shown that gold nanostructures generate transient nanobubbles through localized heating and have been found in various biomedical applications. However, the current method of plasmonic nanoparticle cavitation events has several disadvantages, specifically including small metal nanostructures (≤10 nm) which lack size control, tuneability, and tissue localization by use of ultrashort pulses (ns, ps) and high-energy lasers which can result in tissue and cellular damage. This research investigates a method to immobilize sub-10 nm AuNPs (3.5 and 5 nm) onto a chemically modified thiol-rich surface of Qß virus-like particles. These findings demonstrate that the multivalent display of sub-10 nm gold nanoparticles (AuNPs) caused a profound and disproportionate increase in photocavitation by upward of 5-7-fold and significantly lowered the laser fluency by 4-fold when compared to individual sub-10 nm AuNPs. Furthermore, computational modeling showed that the cooling time of QßAuNP scaffolds is significantly extended than that of individual AuNPs, proving greater control of laser fluency and nanobubble generation as seen in the experimental data. Ultimately, these findings showed how QßAuNP composites are more effective at nanobubble generation than current methods of plasmonic nanoparticle cavitation.

Echocardiographic Mitral Annular Calcification is Associated With Atrial Fibrillation Recurrence After Catheter Ablation.

There is a significant relation between mitral annular calcification (MAC) and the development of atrial fibrillation (AF) and major adverse cardiovascular events. However, the influence of MAC on the outcome of AF ablation remains unknown. The study cohort included 785 consecutive patients who underwent successful ablation. AF recurrence was monitored 3 months after ablation. Cox proportional hazards models were used to assess the association between MAC and AF recurrence. Kaplan-Meier analysis was performed to calculate the incidence of AF recurrence. Over a follow-up period of 16 ± 10 months, 190 patients (24.2%) experienced AF recurrence after ablation. MAC by echocardiography was identified in 42 patients (22%) with AF recurrence but only 60 without (10%, p <0.001). Patients with MAC were older (p <0.001), more often women (p <0.001), with a higher prevalence of hypertension (p <0.001) and diabetes mellitus (p<0.001), moderate/severe mitral regurgitation (p <0.001), larger left atrial dimension (p <0.001), and higher CHA2DS2-VASc score (p <0.001). Patients with MAC were more likely to develop AF recurrence than those without (36% vs 22%, respectively, p = 0.002). MAC was significantly associated with AF recurrence in the unadjusted analysis (hazard ratio 1.77, 95% confidence interval 1.26 to 2.58, p <0.001) and remained statistically significant after the multivariate adjustment (hazard ratio 1.48, 95% confidence interval 1.13 to 1.95, p = 0.001). In conclusion, echocardiographic MAC is significantly associated with an increased risk of AF recurrence after successful ablation, demonstrating an independent predictive value other than the established risk factors.

Influences of environment, human activity, and climate on the invasion of Ageratina adenophora (Spreng.) in Southwest China.

With economic and social globalization, invasive alien species have significantly threatened local ecological security. Identifying the invasive mechanisms of invasive alien species can aid in preventing species invasions and protecting local ecological and economic security. As a globally invasive plant, Ageratina adenophora (Asteraceae) has spread to many parts of the world and had a seriously impacted the ecology and economy of its invaded areas. Using observational data and Landsat OLI images in an arid valley region in southwest China, this study examined how climate, human activity and environmental factors influence the invasion of A. adenophora and its underlying mechanism. Our results showed that the invasion abundance of A. adenophora was significantly affected by environmental factors (the relative importance was 87.2%), but was less influenced by human activity and climate factors (the relative importance was 2% and 10.8%, respectively). The A. adenophora abundance significantly decreased with aspect, community canopy density, shrub layer coverage, herb layer coverage, Simpson diversity index of shrub and herb layers, the shortest distance to residential areas and temperature seasonality, whereas it increased with soil moisture, temperature annual range, precipitation of wettest month and precipitation of driest month. We conclude that biotic competition is the most influential factor in the invasion of this plant in the arid valley regions. Our results are of great significance for invasion prevention and forest conservation and management in southwest China. Our work emphasized that optimizing the community structure, such as by increasing canopy and shrub coverage and species biodiversity, may help control and mitigate the A. adenophora invasion in southwest China.

Integrated Analysis of Gut Microbiome and Liver Metabolome to Evaluate the Effects of Fecal Microbiota Transplantation on Lipopolysaccharide/D-galactosamine-Induced Acute Liver Injury in Mice.

Acute liver failure (ALF) refers to the occurrence of massive hepatocyte necrosis in a short time, with multiple complications, including inflammatory response, hepatic encephalopathy, and multiple organ failure. Additionally, effective therapies for ALF are lacking. There exists a relationship between the human intestinal microbiota and liver, so intestinal microbiota modulation may be a strategy for therapy of hepatic diseases. In previous studies, fecal microbiota transplantation (FMT) from fit donors has been used to modulate intestinal microbiota widely. Here, we established a mouse model of lipopolysaccharide (LPS)/D-galactosamine (D-gal) induced ALF to explore the preventive and therapeutic effects of FMT, and its mechanism of action. We found that FMT decreased hepatic aminotransferase activity and serum total bilirubin levels, and decreased hepatic pro-inflammatory cytokines in LPS/D-gal challenged mice (p < 0.05). Moreover, FMT gavage ameliorated LPS/D-gal induced liver apoptosis and markedly reduced cleaved caspase-3 levels, and improved histopathological features of the liver. FMT gavage also restored LPS/D-gal-evoked gut microbiota dysbiosis by modifying the colonic microbial composition, improving the abundance of unclassified_o_Bacteroidales (p < 0.001), norank_f_Muribaculaceae (p < 0.001), and Prevotellaceae_UCG-001 (p < 0.001), while reducing that of Lactobacillus (p < 0.05) and unclassified_f_Lachnospiraceae (p < 0.05). Metabolomics analysis revealed that FMT significantly altered LPS/D-gal induced disordered liver metabolites. Pearson's correlation revealed strong correlations between microbiota composition and liver metabolites. Our findings suggest that FMT ameliorate ALF by modulating gut microbiota and liver metabolism, and can used as a potential preventive and therapeutic strategy for ALF.

Up-regulation of PUM1 by miR-218-5p promotes colorectal tumor-initiating cell properties and tumorigenesis by regulating the PI3K/AKT axis.

Background: Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of cancer-related death worldwide. Advanced stage CRC, during the recent past, had a dismal prognosis and only a few available treatments. Pumilio homologous protein 1 (PUM1) is reportedly aberrant in human malignancies, including CRC. However, the role of PUM1 in the regulation of tumor-initiating cells (T-ICs) remains unknown. Methods: The levels of messenger RNAs (mRNAs) were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunoblot analyses. Statistical analyses were performed to determine the associations between the levels of PUM1 and tumor features and patient outcomes. Whether PUM1 is a downstream target of miR-218-5p was verified by bioinformatics target gene prediction and qRT-PCR. Results: Herein, it was found that T-ICs, chemoresistance, and recurrent CRC samples all manifest increased PUM1 expression. Functional investigations have shown that PUM1 increased the self-renewal, tumorigenicity, malignant proliferation, and chemoresistance of colorectal cells. PUM1 activates the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway biochemically. Furthermore, it was discovered that miR-218-5p specifically targets T-ICs' PUM1 3'-untranslated region (3'-UTR). More importantly, the PUM1/PI3K/AKT axis regulates CRC cells' responses to treatment with cetuximab, and PUM1 overexpression increased cetuximab resistance. More evidence points to the possibility that low PUM1 may predict cetuximab benefits in CRC patients after analysis of the patient cohort, patient-derived tumor organoids, and patient-derived xenografts (PDXs). Conclusions: Taken together, the result of this work points to the critical function of the miR-218-5p/PUM1/PI3K/AKT regulatory circuit in regulating T-ICs characteristics and thus suggests possible therapeutic targets for CRC.

Mutual regulation between glycosylation and transforming growth factor-ß isoforms signaling pathway.

Transforming growth factor-beta (TGF-ß) superfamily members orchestrate a wide breadth of biological processes. Through Sma and Mad (Smad)-related dependent or noncanonical pathways, TGF-ß members involve in the occurrence and development of many diseases such as cancers, fibrosis, autoimmune diseases, cardiovascular diseases and brain diseases. Glycosylation is one kind of the most common posttranslational modifications on proteins or lipids. Abnormal protein glycosylation can lead to protein malfunction and biological process disorder, thereby causing serious diseases. Previously, researchers commonly make comprehensive systematic overviews on the roles of TGF-ß signaling in a specific disease or biological process. In recent years, more and more evidences associate glycosylation modification with TGF-ß signaling pathway, and we can no longer disengage and ignore the roles of glycosylation from TGF-ß signaling to make investigation. In this review, we provide an overview of current findings involved in glycosylation within TGF-ßs and theirs receptors, and the interaction effects between glycosylation and TGF-ß subfamily signaling, concluding that there is an intricate mutual regulation between glycosylation and TGF-ß signaling, hoping to present the glycosylation regulatory patterns that concealed in TGF-ßs signaling pathways.

Intrafibrillar Mineralization and Immunomodulatory for Synergetic Enhancement of Bone Regeneration via Calcium Phosphate Nanocluster Scaffold.

Inspired by the bionic mineralization theory, organic-inorganic composites with hydroxyapatite nanorods orderly arranged along collagen fibrils have attracted extensive attention. Planted with an ideal bone scaffold will contribute greatly to the osteogenic microenvironment; however, it remains challenging to develop a biomimetic scaffold with the ability to promote intrafibrillar mineralization and simultaneous regulation of immune microenvironment in situ. To overcome these challenges, a scaffold containing ultra-small particle size calcium phosphate nanocluster (UsCCP) is prepared, which can enhance bone regeneration through the synergetic effect of intrafibrillar mineralization and immunomodulatory. By efficient infiltration into collagen fibrils, the UsCCP released from the scaffold achieves intrafibrillar mineralization. It also promotes the M2-type polarization of macrophages, leading to an immune microenvironment with both osteogenic and angiogenic potential. The results confirm that the UsCCP scaffold has both intrafibrillar mineralization and immunomodulatory effects, making it a promising candidate for bone regeneration.

Top-Emission ZnSeTe/ZnSe/ZnS-Based Blue Quantum Dot Light-Emitting Diodes with Enhanced Chroma Efficiency.

A high-performance quantum dot light-emitting diode (QLED) with heavy metal free (HMF) quantum dots (QDs) is urgently needed for its application in next-generation eco-friendly displays. However, the preparation of high-performance HMF QD materials and the corresponding electroluminescent devices remain challenges at present, especially for blue-emitting devices. In this work, by adjusting the Te/Se ratio of the ZnSeTe core, ZnSeTe/ZnSe/ZnS blue QDs with adjustable energy levels and emission peaks are demonstrated. These QDs are utilized to fabricate top-emitting QLEDs, yielding a peak current efficiency (CE) of 11.8 cd A-1. To make it one step further to meet the requirement of the wide color gamut in displays, the devices' color coordinates and current efficiency are simultaneously optimized by adjusting their microcavity structure and electrical properties. Finally, the chroma efficiency (current efficiency/CIEy) of the blue devices is optimized to 72, which is 2.2 times that of the control device.

Disentangling environmental effects on picophytoplankton communities in the Eastern Indian Ocean.

Photosynthesis by picophytoplankton provides energy for higher organisms and is essential in the food chain and global carbon cycle. In 2020 and 2021, we investigated the spatial distribution and vertical changes of picophytoplankton in the euphotic layer of the Eastern Indian Ocean (EIO) and estimated their carbon biomass contributions through two cruise surveys. The abundance of picophytoplankton was composed of Prochlorococcus (69.94%), Synechococcus (22.21%) and picoeukaryotes (7.85%). Synechococcus was mainly found in the surface layer, while Prochlorococcus and picoeukaryotes had high abundances in the subsurface layer. The surface picophytoplankton community was greatly affected by fluorescence, the middle layer was significantly regulated by temperature and dissolved oxygen concentration, and the lower layer was dominated by nutrients and apparent oxygen utilization (AOU). Aggregated boosted tree (ABT) and Generalized Additive models (GAM) indicated that temperature, salinity, AOU, and fluorescence were strong influencing factors of picophytoplankton communities in EIO. The mean carbon biomass contribution of picophytoplankton in the surveyed area was 0.565 µg C/L, which was contributed by Prochlorococcus (39.32%), Synechococcus (38.88%) and picoeukaryotes (21.80%). These findings contribute to our understanding of the effects of different environmental factors on picophytoplankton communities and the influence of picophytoplankton contributions to the carbon pools of the oligotrophic ocean.

Effect and Mechanism of lncRNA-PCMF1/hsa-miR-137/Twist1 Axis Involved in the EMT Regulation of Prostate Cancer Cells.

The metastasis is a major reason for the poor prognosis of the patients with prostate cancer (PC). Currently, androgen deprivation therapy (ADT) is the basic method for the treatment of PC regardless of surgery or drug treatments. However, ADT therapy is generally not recommended for patients with advanced/metastatic PC. Herein, we report for the first time a long non-coding RNA (lncRNA)-PCMF1 which promotes the progression of Epithelial-Mesenchymal Transition (EMT) in PC cells. Our data demonstrated that PCMF1 in metastatic PC tissues increased significantly compared to non-metastatic specimens. Mechanism research showed that PCMF1 could competitively bind to hsa-miR-137 instead of the 3' -Untranslated Region (UTR) of Twist Family BHLH Transcription Factor 1 (Twist1) by acting as an endogenous miRNA sponge. Furthermore, we found that silence of PCMF1 effectively blocked the EMT in PC cells by indirectly suppressing Twist1 protein mediated by hsa-miR-137 at post-transcriptional level. In summary, our research shows that PCMF1 promotes the EMT of PC cells by causing the functional inactivation of hsa-miR-137 on Twist1 protein, which is an independent risk factor of PC. PCMF1 knockdown combined with hsa-miR-137 expression is a promising PC-targeted therapy. Furthermore, PCMF1 is also expected to act as a useful marker for predicting malignant changes and assessing the prognosis of PC patients.

Outcomes of intravenous and inhalation anesthesia on patients undergoing esophageal cancer surgery: a retrospective observational study.

BACKGROUND: Different anesthetics may have opposite effects on the immune system, thus affecting the prognosis of tumor patients. Cell-mediated immunity forms the primary defense against the invasion of tumor cells, so manipulation of the immune system to produce an enhanced anti-tumor response could be utilized as an adjuvant oncological therapy. Sevoflurane has proinflammatory effects, while propofol, has anti-inflammatory and antioxidant effects. Therefore, we compared the overall survival (OS) and disease-free survival (DFS) of patients with esophageal cancer under total intravenous anesthesia and inhalation anesthesia. METHODS: This study collected the electronic medical records of patients undergoing esophagectomy from January 1, 2014 to December 31, 2016. According to the intraoperative anesthetics, the patients were divided into total intravenous anesthesia (TIVA) group or inhalational anesthesia (INHA) group. Stabilized inverse probability of treatment weighting (SIPTW) was used to minimize differences. Kaplan-Meier survival curve was established to evaluate the correlation between different anesthesia methods in overall survival and disease-free survival of patients undergoing esophageal cancer surgery. RESULTS: A total of 420 patients with elective esophageal cancer were collected, including 363 patients eligible for study (TIVA, n = 147, INHA, n = 216). After SIPTW there were no significant differences between two groups in overall survival and disease-free survival. However, the adjuvant therapy was statistically significant in improving OS, and the degree of differentiation was correlated with OS and DFS. CONCLUSIONS: In conclusion, there were no significant difference in overall survival and disease-free survival between total intravenous anesthesia and inhalational anesthesia in patients undergoing esophageal cancer surgery.

Penalty mitigation for OSC-induced XPM in long-haul WDM coherent systems by digital up-conversion coding.

Due to the cross phase modulation (XPM) effect, in long-haul high-speed dense wavelength division multiplexing (DWDM) coherent systems, using a low-speed on-off-keying (OOK) format optical supervisory channel (OSC) will introduce extra nonlinear phase noise, which restricts the transmission distance. In this paper, we propose a simple OSC coding method to mitigate the OSC-induced nonlinear phase noise. According to the split-step solution of the Manakov equation, we up-convert the baseband of the OSC signal out of the pass-band of the walk-off term to reduce the spectrum density of XPM phase noise. Experimental results show that the optical signal to noise ratio (OSNR) budget on the 400 G channel of 1280-km transmission is improved by 0.96 dB, which achieves almost the same performance with the no OSC case.

Pulmonary artery smooth muscle cell phenotypic switching: A key event in the early stage of pulmonary artery hypertension.

Pulmonary arterial hypertension (PAH) is a currently incurable pulmonary vascular disease. Since current research on PAH is mainly aimed at the middle and late stages of disease progression, no satisfactory results have been achieved. This has led researchers to focus on the early stages of PAH. This review highlights for the first time a key event in the early stages of PAH progression, namely, the occurrence of pulmonary arterial smooth muscle cell (PASMC) phenotypic switching. Summarizing the related reports of performance conversion provides new perspectives and directions for the early pathological progression and treatment strategies for PAH.

QSP: An open sequence database for quorum sensing related gene analysis with an automatic annotation pipeline.

Quorum sensing (QS) has attracted great attention due to its important role in the bacterial interactions and its relevance to water management. With the development of high-throughput sequencing technology, a specific database for QS-related sequence annotation is urgently needed. Here, Hidden Markov Model (HMM) profiles for 38 types of QS-related proteins were built using a total of 4024 collected seed sequences. Based on both homolog search and keywords confirmation against the non-redundant database, we established a QS-related protein (QSP) database, that includes 809,721 protein sequences and 186,133 nucleotide sequences, downloaded available at: https://github.com/chunxiao-dcx/QSP. The entries were classified into 38 types and 315 subtypes among 91 bacterial phyla. Furthermore, an automatic annotation pipeline, named QSAP, was developed for rapid annotation, classification and abundance quantification of QSP-like sequences from sequencing data. This pipeline provided the two homolog alignment strategies offered by Diamond (Blastp) or HMMER (Hmmscan), as well as a data cleansing function for a subset or union set of the hits. The pipeline was tested using 14 metagenomic samples from various water environments, including activated sludge, deep-sea sediments, estuary water, and reservoir water. The QSAP pipeline is freely available for academic use in the code repository at: https://github.com/chunxiao-dcx/QSAP. The establishment of this database and pipeline, provides a useful tool for QS-related sequence annotation in a wide range of projects, and will increase our understanding of QS communication in aquatic environments.

Effect of triple therapy with low-dose total body irradiation and hypo-fractionated radiation plus anti-programmed cell death protein 1 blockade on abscopal antitumor immune responses in breast cancer.

Immunostimulatory effects of radiotherapy can be synergistically augmented with immune checkpoint blockade to act both on irradiated tumor lesions and distant, non-irradiated tumor sites. Our hypothesis was that low-dose total body irradiation (L-TBI) combined with hypo-fractionated radiotherapy (H-RT) and anti-programmed cell death protein 1 (aPD-1) checkpoint blockade would enhance the systemic immune response. We tested the efficacy of this triple therapy (L-TBI + H-RT + aPD-1) in BALB/c mice with bilateral breast cancer xenografts. The L-TBI dose was 0.1 Gy. The primary tumor was treated with H-RT (8 Gy × 3). The PD-1 monoclonal antibody was injected intraperitoneally, and the secondary tumors not receiving H-RT were monitored for response. The triple therapy significantly delayed both primary and secondary tumor growths, improved survival rates, and reduced the number of lung metastasis lesions. It increased the activated dendritic and CD8+ T cell populations and reduced the infiltration of myeloid-derived suppressor cells in the secondary tumor microenvironment relative to other groups. Thus, L-TBI could be a potential therapeutic modality, and when combined with H-RT and aPD-1, the therapeutic effect could be enhanced significantly.

Critical minority fractions causing membrane fouling in reclaimed water: Fouling characteristics, mechanisms and control strategies.

In regard to membrane-based technologies of wastewater reclamation, the reported key foulants were faced with dilemma that they could not be effectively separated and extracted from reclaimed water for thorough investigation. In this study, the crucial foulants were proposed as "critical minority fraction (FCM)", representing the fraction with molecular weight (MW) > 100 kDa which could be easily separated by physical filtration using MW cut-off membrane of 100 kDa with fairly high recovery ratio. FCM with low dissolved organic carbon (DOC) concentration (∼1 mg/L) accounted for less than 20% of the total DOC in reclaimed water, while contributed to more than 90% of the membrane fouling, and thus FCM could be considered as a "perfect criminal" causing membrane fouling. Furthermore, pivotal fouling mechanism was attributed to the significant attractive force between FCM and membranes, which led to severe fouling development due to the aggregation of FCM on membrane surface. Fluorescent chromophores of FCM were concentrated in regions of proteins and soluble microbial products, with proteins and polysaccharides accounted for 45.2% and 25.1% of the total DOC, specifically. FCM was further fractionated into six fractions, among which hydrophobic acids and hydrophobic neutrals were the dominant components in terms of DOC content (∼80%) as well as fouling contribution. Regarding to these pronounced properties of FCM, targeted fouling control strategies including ozonation and coagulation were applied and proved to achieve remarkable fouling control effect. High-performance size-exclusion chromatography results suggested that ozonation achieved distinct transformation of FCM into low MW fractions, while coagulation removed FCM directly, thus leading to effective fouling alleviation. Therefore, the investigation of the critical foulants was expected to help glean valuable insight into the fouling mechanism and develop targeted fouling control technologies in practical applications.