Clinical outcomes of coronavirus disease in patients with breast cancer treated with granulocyte colony-stimulating factor following chemotherapy: Triangulation of evidence using population-based cohort and Mendelian randomization analyses.

Recombinant human granulocyte colony-stimulating factor (G-CSF) administration in patients with cancer and coronavirus disease (COVID-19) remains controversial. Concerns exist that it may worsen COVID-19 outcomes by triggering an inflammatory cytokine storm, despite its common use for managing chemotherapy-induced neutropenia (CIN) or febrile neutropenia post-chemotherapy. Here, we determined whether prophylactic or therapeutic G-CSF administration following chemotherapy exacerbates COVID-19 progression to severe/critical conditions in breast cancer patients with COVID-19. Between December 2022 and February 2023, all 503 enrolled breast cancer patients had concurrent COVID-19 and received G-CSF post-chemotherapy, with most being vaccinated pre-chemotherapy. We prospectively observed COVID-19-related adverse outcomes, conducted association analyses, and subsequently performed Mendelian randomization (MR) analyses to validate the causal effect of genetically predicted G-CSF or its associated granulocyte traits on COVID-19 adverse outcomes. Only 0.99% (5/503) of breast cancer patients experienced COVID-19-related hospitalization following prophylactic or therapeutic G-CSF administration after chemotherapy. No mortality or progression to severe/critical COVID-19 occurred after G-CSF administration. Notably, no significant associations were observed between the application, dosage, or response to G-CSF and COVID-19-related hospitalization (all p >.05). Similarly, the MR analyses showed no evidence of causality of genetically predicted G-CSF or related granulocyte traits on COVID-19-related hospitalization or COVID-19 severity (all p >.05). There is insufficient evidence to substantiate the notion that the prophylactic or therapeutic administration of G-CSF after chemotherapy for managing CIN in patients with breast cancer and COVID-19 would worsen COVID-19 outcomes, leading to severe or critical conditions, or even death, especially considering the context of COVID-19 vaccination.

Mechanisms of acid generation from ionic photoacid generators for extreme ultraviolet and electron beam lithography.

Photoacid generators (PAGs) are important components of chemically amplified resists. The properties of PAGs directly affect the sensitivity of photoresists, line edge roughness, and resolution. Understanding the photoacid generation process in extreme ultraviolet (EUV) and electron beam (EB) lithography is helpful for photoresist design. However, the microscopic mechanisms remain largely unclear and the large variety in the molecular structure of PAGs presents a challenge to overcome. In this work, we investigate the microscopic processes of photoacid production of ionic PAGs for EUV and EB lithography. The PAG dissociation pathway is found to depend on the molecular structure and conformations. The processes of photoacid production and by-product generation are also revealed. The results contribute to a better understanding of the photochemical reactions in EUV and EB lithography, providing insights into the molecular design of novel PAGs and photoresists.

Fabrication of lanthanum/chitosan co-modified bentonite and phosphorus removal mechanism from low-concentration landscape water.

It is essential to solve the problem of phosphorus pollution in urban landscape water and reduce the degree of eutrophication. In this paper, lanthanum-modified bentonite (La-B) was prepared by high-temperature calcination and liquid-phase precipitation. Then La-B was modified with chitosan to prepare a low-cost environment-friendly functional material: lanthanum/chitosan co-modified bentonite (La-BC). It can reach the adsorption equilibrium within 30 min, and the maximum adsorption capacity is 15.5 mg/g (initial phosphate concentration 50 mg/L); when the target concentration is 2 mg/L, the removal rate can reach 98.5%. La-BC has a stronger anti-interference ability to common coexisting anions SO42-, HCO3-, NO3- and Cl- in the urban landscape water body. La-BC has excellent performance in weakly acidic to neutral water, and its pH applicable range has been improved, making it possible to apply in practical water. The fitting results show that the adsorption behavior conforms to the pseudo-second-order kinetic model and the Freundlich model. After 5 regenerations, the removal efficiency remained around 80%. In the actual water test results, the phosphate concentration can be controlled below 0.1 mg/L and the removal rate is above 75%. Due to its low cost and reusability, it has great potential in the practical application of phosphate removal from landscape water.

Circulation patterns and seed-soil compatibility factors cooperate to cause cancer organ-specific metastasis.

Despite the recognition of the lethality of cancer metastasis and the importance of developing specific anti-metastasis therapies directed at the cancer metastatic cascade, the dynamics of cancer metastasis remains poorly understood. In this study, we examined the dynamics of circulating tumor cell (CTC) survival in the bloodstream using experimental mouse models. CTCs were arrested in the capillaries by adhesion to vascular endothelium within a few minutes after injection into the bloodstream. The loss of CTCs from the circulation followed a bi-phasic decay pattern, with the number of CTCs in the bloodstream being closely associated with the number of blood circulation cycles. The calculated in vivo Vd (apparent volume of distribution) of the CTC revealed organ specific binding of the CTCs. Moreover, confocal microscopy, in vivo fluorescence imaging in syngeneic mouse metastatic models and analysis of blood circulation patterns support the notion of organ-specific tumor metastasis. The present study suggests that organ-specific tumor metastasis is influenced by cooperation between blood circulation patterns and 'seed-soil' compatibility factors. These new findings provide further insights for optimized cancer metastatic prevention strategies such as by creating a hostile circulation microenvironment and targeting the organ-specific 'seed-soil' compatibility factors.

Interlayer manipulation of bio-inspired Ti3C2Tx nanocontainer through intercalation of amino acid molecules to dramatically boosting uranyl hijacking capability from seawater.

More than 4.5 billion tons of unconventional uranium resources [UO2(CO3)3]4- are uniformly dissolved in seawater, providing a sustainable and abundant fuel source for the development of nuclear energy. Herein, we presented a rational design and development of Ti3C2Tx nanocontainer inspired by the exceptional selectivity and affinity exhibited by superb-uranyl proteins through amino acid intercalation. The amino acid intercalation of Ti3C2Tx demonstrated exceptional UO22+ capture capacity (Arg-Ti3C2Tx, His-Ti3C2Tx, and Lys-Ti3C2Tx with qmax values of 594.46, 846.04, and 1030.17 mg/g). Furthermore, these intercalated materials exhibited remarkable sequestration efficiency and selectivity (Uinitial = ∼45.2 ∼7636 µg/L; ∼84.45% ∼98.08%; and ∼2.72 ×104 ∼1.28 ×105 KdU value), despite the presence of an overwhelming surplus of Na+, Ca2+, Mg2+, and Co2+ ions. Significantly, even in the 0.3 M NaHCO3 solution and surpassing 103-fold of the Na3VO4 system, the adsorption efficiency of Lys-Ti3C2Tx still achieved a remarkable 63.73% and 65.05%. Moreover, the Lys-Ti3C2Tx can extract ∼30.23 ∼8664.03 µg/g uranium after 24 h contact in ∼13.3 ∼5000 µg/L concentration from uranium-spiked natural seawater. The mechanism analysis revealed that the high binding capability can be attributed to the chelation of carboxyl and amino groups with uranyl ions. This innovative state-of-the-art approach in regulating uranium harvesting capability through intercalation of amino acid molecules provides novel insights for extracting uranium from seawater.

Enhancing Pd Catalytic Activity by Amine Group Modification for Efficient Direct Synthesis of H2O2.

A great deal of research has been carried out on the design of Pd-based catalysts in the direct synthesis of H2O2, mainly for the purpose of improving the H2O2 selectivity by weakening the activation energy on the Pd active site and thus inhibiting the dissociation of the O-O bonds in O2*, OOH*, and HOOH*. However, this often results in insufficient activation energy for the reaction between H2 and O2 on Pd, leading to difficulties in improving both the selectivity and productivity of H2O2 simultaneously. Based on this, this study reports an efficient catalyst composed of amine-functionalized SBA-15-supported Pd. The strong metal-support interaction not only makes the PdNPs highly dispersed with more Pd active sites but also improves the stability of the catalyst. The amine group modification increases the proportion of Pd0, further enhancing Pd activity and promoting the adsorption and conversion of H2 and O2 on Pd, thereby significantly increasing H2O2 productivity. Additionally, the density-functional theory simulation results showed that due to the hydrogen-bonding force between the amine group and H2O2, this particular anchoring effect would make the hydrogenation and decomposition of H2O2 effectively suppressed. Ultimately, both the selectivity and productivity of H2O2 are improved simultaneously.

Clinical characteristics and overall survival prognostic nomogram for metaplastic breast cancer.

Background: Metaplastic breast cancer (MBC) is a rare breast tumor and the prognostic factors for survival in patients still remain controversial. This study aims to develop and validate a nomogram to predict the overall survival (OS) of patients with MBC. Methods: We searched the Surveillance, Epidemiology, and End Results (SEER) database for data about patients including metaplastic breast cancer and infiltrating ductal carcinoma (IDC) from 2010 to 2018. The survival outcomes of patients between MBC and IDC were analyzed and compared with the Kaplan-Meier (KM) method. MBC patients were randomly allocated to the training set and validation I set by a ratio of eight to two. Meanwhile, the performance of this model was validated again by the validation II set, which consisted of MBC patients from the Union Hospital of Fujian Medical University between 2010 and 2018. The independent prognostic factors were selected by univariate and multivariate Cox regression analyses. The nomogram was constructed to predict individual survival outcomes for MBC patients. The discriminative power, calibration, and clinical effectiveness of the nomogram were evaluated by the concordance index (C-index), the receiver operating characteristic (ROC) curve, and the decision curve analysis (DCA). Results: MBC had a significantly higher T stage (T2 and above accounting for 75.1% vs 39.9%), fewer infiltrated lymph nodes (N0 accounted for 76.2% vs 67.7%), a lower proportion of ER (22.2% vs 81.2%), PR (13.6% vs 71.4%), and HER-2(6.7% vs 17.7%) positive, radiotherapy(51.6% vs 58.0%) but more chemotherapy(67.5% vs 44.7%), and a higher rate of mastectomy(53.2% vs 36.8%), which was discovered when comparing the clinical baseline data between MBC and IDC. Age at diagnosis, T, N, and M stage, as well as surgery and radiation treatment, were all significant independent prognostic factors for overall survival (OS). In the validation I cohort, the nomogram's C-index (0.769 95% CI 0.710 -0.828) was indicated to be considerably higher than the standard AJCC model's (0.700 95% CI 0.644 -0.756). Nomogram's great predictive capability capacity further was supported by the comparatively high C-index of the validation II sets (0.728 95%CI 0.588-0.869). Conclusions: Metaplastic breast cancer is more aggressive, with a worse clinical prognosis than IDC. This nomogram is recommended for patients with MBC, both American and Chinese, which can help clinicians make more accurate individualized survival analyses.

Nitrogen removal by a strengthened comprehensive floating bed with embedded pellets made by a newly isolated Pseudomonas sp. Y1.

A newly heterotrophic nitrification aerobic denitrification(HN-AD) bacterium Pseudomonas sp. Y1 with highly nitrogen removal ability was isolated from the activated sludge, TN removal rate of which was 99.73%. In this study, two types of different ecology floating bed systems were designed to achieve efficient nitrogen removal in the urban eutrophic landscape water body, one is the comprehensive ecological floating bed(CEFB) system with only Lythrum salicari and the other is the strengthened comprehensive ecological floating bed (SCEFB) system with both Lythrum and embedded pellets made by Y1. The TN removal rates of the CEFB system were 33.82%, 83.84% and 88.91% at 8±1℃, 15±1℃ and 25±1℃, respectively, while the TN removal rates of the SCEFB system increased by nearly 40%, 16% and 11% at the same environment, respectively. The result shows that the SCEFB system can purify the simulated water from surface water body class V to class IV. Thus it has a broad application prospect in the urban eutrophic landscape water body.

The role of nitro group on the excited-state relaxation mechanism of P-Z base pair.

DNAs' photostability is significant to the normal function of organisms. P-Z is a hydrogen bonded artificial DNA base pair, where P and Z represent 2-amino-imidazo[1,2-a]-1,3,5-triazin-4(8H)one and 6-amino-5nitro-2(1H)-pyridone, respectively. The excited-state relaxation mechanism of P-Z pair is investigated using static TDDFT calculations combined with the non-adiabatic dynamic simulations at TDDFT level. The roles of nitro rotation, nitro out-of-plane deformation, and single proton transfer (SPT) along hydrogen bond are revealed. The results of potential energy profile calculations demonstrate that the SPT processes along the hydrogen bonds are unfavorable to occur statically, which is in great contrast to the natural base pair. The non-adiabatic dynamic simulations show that the excited-state nitro rotation and nitro out-of-plane deformation are the two important relaxation channels which lead to the fast internal conversion to S0 state. The SPT from Z to P is also observed, followed by distortion on P, inducing the fast internal conversion to S0 state. However, this channel (decay via SPT process) plays minor roles on the excited-state relaxation mechanism statistically. This work shows the great differences of the excited-state relaxation mechanism between the natural base pairs and artificial base pair, also sheds new light into the role of hydrogen bond and nitro group in P-Z base pair.

Diabetes remission after a lifestyle-medicine intervention on type 2 diabetes in lean and obese Chinese subjects: a prospective study.

BACKGROUND: Whether diabetes remission still happened among non-obese type 2 diabetes (T2DM) patients with a body mass index (BMI) <25 kg/m2 following lifestyle-medicine interventions was quite necessary to be reported because many diabetes happened with normal or low BMI in China. METHODS: The criteria for subject inclusion: <20 years after T2DM diagnosis, ≥6 months treatment with oral anti-diabetic drugs, without serious complications, and no history of insulin use. They were divided into two groups: the obesity group (BMI ≥25 kg/m2) and the lean group (BMI <25 kg/m2). All subjects received the following lifestyle-medicine interventions: stopping oral anti-diabetic therapy, initiating a low-carbohydrate (contributing by 35-40% to calorie intake) diet for the first month (gradual transition to a normal diet for the next 5 months), participating in resistance and aerobic exercise, and receiving strengthen management. Diabetes remission was defined as glycosylated hemoglobin (A1C) level <6.5% (<48 mmol/mol) after 6 months of not taking any anti-diabetic medications during the lifestyle-medicine intervention. Finally, 125 individuals completed the lifestyle-medicine intervention in the prospective study. The efficacy and safety of lifestyle-medicine intervention were assessed and compared between lean and obese Chinese subjects with T2DM. RESULTS: We found that 64.52% of the T2DM subjects in the obese group and 60.64% of T2DM subjects in the lean group achieved diabetes remission [i.e., an A1C level <6.5% (48 mmol/mol)] without any anti-diabetic medications after the 6-month lifestyle-medicine intervention. Our multiple linear regression analysis showed that decreases in the fasting plasma glucose (FPG) level had the most powerful effect on decreases in the A1C level after the intervention (R2=0.3072). CONCLUSIONS: Lifestyle-medicine interventions may have increased effectiveness in controlling mild T2DM as compared with the oral antidiabetic-based treatment; unexpectedly, there seems no further improvement in lean relative to obese patients. Three in five subjects could achieve diabetes remission though the lifestyle-medicine intervention regardless of whether their BMI was below or above 25 kg/m2.

Fucoxanthin prevents breast cancer metastasis by interrupting circulating tumor cells adhesion and transendothelial migration.

Metastasis is the leading cause of cancer-related death and a critical challenge in improving cancer treatment today. Circulating tumor cells (CTCs) adhesion to and across the vascular endothelium are critical steps in the establishment of micrometastatic foci away from the primary tumor. Therefore, we believe that interrupting CTCs adhesion to endothelium and transendothelial migration may efficiently prevent cancer metastasis. Fucoxanthin (Fx) is an algal carotenoid widely distributed in brown algae, macroalgae, and diatoms. Previous studies have found that Fx has various pharmacological activities, including antidiabetic, antioxidant, anti-inflammatory, anti-obesity, antimalarial, anticancer, and so on. However, it remains unclear whether Fx has a preventive effect on cancer metastasis. Here, we found that Fx interrupts breast cancer cells MCF-7 adhesion to endothelium and transendothelial migration, thus inhibiting CTCs-based pulmonary metastasis in vivo. The hetero-adhesion assay showed that Fx significantly inhibited the expression of inflammatory factor-induced cell adhesion molecules (CAMs) and the resulting adhesion between MCF-7 cells and endothelial cells. The wound-healing and transwell assays showed that Fx significantly inhibited the motility, invasion, and transendothelial migration abilities of MCF-7 cells. However, the same concentration of Fx did not significantly alter the cell viability, cell cycle, apoptosis, and ROS of breast cancer cells, thus excluding the possibility that Fx inhibits MCF-7 cell adhesion and transendothelial migration through cytotoxicity. Mechanistically, Fx inhibits the expression of CAMs on endothelial cells by inhibiting the NF-кB signaling pathway by down-regulating the phosphorylation level of IKK-α/ß, IкB-α, and NF-кB p65. Fx inhibits transendothelial migration of MCF-7 cells by inhibiting Epithelial-to-mesenchymal transition (EMT), PI3K/AKT, and FAK/Paxillin signaling pathways. Moreover, we demonstrated that Fx significantly inhibits the formation of lung micrometastatic foci in immunocompetent syngeneic mouse breast cancer metastasis models. We also showed that Fx enhances antitumor immune responses by substantially increasing the subsets of cytotoxic T lymphocytes in the peripheral immune system. This new finding provides a basis for the application of Fx in cancer metastatic chemoprevention and suggests that interruption of the CTCs adhesion to endothelium and transendothelial migration may serve as a new avenue for cancer metastatic chemoprevention.

Tumor-derived Exosome Promotes Metastasis via Altering its Phenotype and Inclusions.

Although tumor-derived exosomes play an important role in the process of metastasis, differences in exosomes secreted by the same cells at different stages or conditions have not been noticed by most of the relevant researchers. Here we developed a lung cancer model in nude mice, and the phenotype and inclusions of exosomes secreted by early and advanced tumors were analysed. The size distribution and surface topography of these two exosomes were not significantly different, but the expression of CD63 in early tumor exosome (E-exosome) was significantly lower than that in advanced tumor exosome (A-exosome). α-SMA expression on HELF cells treated with A-exosome was significantly higher than that treated with E-exosome. The ability of A-exosome to promote the migration of A549 cells was better than E-exosome. Furthermore, small RNA sequence showed that only 3 of the 171 detected-small RNAs were expressed simultaneously in both exosomes. These findings proved that there are significant differences in inclusions and functions between the early and late exosomes of the same tumor. The study highlights the importance of exosomes in cancer metastasis, and might suggest exosomes can be used as biomarkers and therapeutic targets for cancer metastasis.

Paragonimus skrjabini Chen, 1959 (Digenea: Paragonimidae) and related species in eastern Asia: a combined molecular and morphological approach to identification and taxonomy.

A molecular and morphometric investigation is reported on the species complex of mammalian lungflukes of which Paragonimus skrjabini Chen, 1959 and P. miyazakii Kamo, Nishida, Hatsushika & Tomimura, 1961 are the best-known examples. This species complex (here called the P. skrjabini complex) is shown to be monophyletic using DNA sequences from the nuclear ITS2 region and the mitochondrial cox1 gene. The latter marker permits the discrimination of populations, some previously named as distinct species, from various geographical locations in China and Japan. Morphometric analysis of a number of variables accords remarkably closely with the molecular results. Main findings are that (1) nominal P.skrjabini from Fujian Province in eastern China is phylogenetically very close to P. miyazakii from Japan. It is proposed that both taxa should be referred to the same subspecies as P. krjabini miyazakii. (2) Populations from Guangdong Province, Guangxi Zhuang Autonomous Region, Sichuan and Hubei should be referred to P. skrjabini skrjabini. Specimens of P. skrjabini from the Yangtze basin in Sichuan and Hubei are remarkably similar to one another according to genetic and morphometric data, but are not so different from Guangdong populations that they should be referred to a different subspecies at this stage. Specimens of P. skrjabini from Yunnan have not been assigned to a subspecies at this stage. (3) Partly following earlier studies, we regard the following as synonyms of P. skrjabini: P. miyazakii (reduced to subspecific status); P. szechuanensis Chung & Tsao, 1962 (probably belongs to P. s. skrjabini); and P. hueitungensis Chung, Hsu, Ho, Kao, Shao, Chiu, Pi, Liu, Ouyang, Shen, Yi & Yao, 1975 (probably belongs to P.s.skrjabini ); P. veocularis (Chen & Li, 1979) (specimens from Fujian regarded as belonging to this species should be referred to P.skrjabini miyazakii: the subspecific status of specimens from the type-locality in northern Sichuan is unclear). A number of questions remain unresolved. The name P. hokuoensis Ho & Chung, 1964 was proposed for two individual metacercariae of distinctive appearance from southern Yunnan. DNA sequences from very similar metacercariae from the same locality place this nominal species within, or sister to, the P. skrjabini complex. As yet, nothing is known regarding adult morphology or biology of this taxon and we retain it here as a distinct species. P. heterorchis (Zhou, Pang & Hsiang, 1982) might be a synonym of P. skrjabini: the form of the metacercaria provides evidence against this view and further work is required. P. macrorchis Chen, 1962 has probably been confused with P. skrjabiniin China. Within China, the former probably occurs only on Hainan Island, although P. fukienensis Tang & Tang, 1962 from Fujian Province could be a synonym.