Inactivation of Bacillus subtilis spores by a combination of high-pressure thermal treatment and potassium sorbate.

Combining High-pressure Thermal Treatment (HPTT) and Potassium Sorbate (PS) may have a stronger spore inactivation effect. Spores of Bacillus subtilis were subjected to HPTT at 600 MPa-65 °C/75 °C and a combination of HPTT and PS of 0.1% and 0.2% concentrations. After these treatments, different procedures and techniques were employed to investigate the spore's inactivation. The results revealed that 4.92 ± 0.05 log spores were inactivated after treatment at 600 MPa-75 °C, while 5.97 ± 0.09 log spores were inactivated when the HPTT treatment was combined with 0.2% PS. Changes in permeability of the spore's inner membrane were characterized by OD600 value and release rates of nucleic acids, protein, and dipicolinic acid (DPA). Compared with HPTT treatment at 600 MPa-75 °C, the OD600 value of spores decreased further by about 50% after treatment with a combination of HPTT and 0.2% PS. Additionally, the combined treatments resulted in a significant increase in the OD260 and OD280 values, as well as the DPA release. The spore size analysis indicated a significant decrease in the size of spores treated with a combination of HPTT at 600 MPa-75 °C and PS of 0.2% concentration. Furthermore, the flow cytometry analysis and confocal laser scanning microscopy (CLSM) analysis indicated that the inner membrane damage of spores was higher after combined treatments than that after HPTT treatment alone. A significant reduction was also found in the Na+/K+-ATPase activity after the combined treatments. Also, the FTIR analysis revealed that the combined treatments resulted in significant adverse changes in the spores' inner membrane, cell wall, cortex, and nucleic acid. Therefore, the combination of HPTT and PS has a stronger inactivation effect and can be suggested as a promising strategy for the inactivation of Bacillus subtilis spores.

Acute fatty liver of pregnancy causing multiple organ dysfunction syndrome in a Chinese intensive care unit.

Acute fatty liver of pregnancy (AFLP) is a rare but severe condition associated with high rates of maternal and foetal morbidity and mortality. Timely discontinuation of pregnancy, professional supervision and appropriate management are helpful for a successful discharge. This article reports the presentation and nursing care of a pregnant woman who was diagnosed with AFLP and discharged from the intensive care unit (ICU) after a prolonged hospitalization. The patient was admitted to the ICU on the first day after a caesarean section, with deterioration of liver, kidney and coagulation function. On day 1 of ICU admission, she underwent transnasal high-flow oxygen therapy. Owing to worsening respiratory status and oxygen saturation <85%, the patient was intubated on day 3 in the ICU. Her urine output decreased significantly, her bilirubin level progressively increased, and she was treated with bilirubin adsorption and haemodialysis. Multiple organ dysfunction syndrome occurred, along with many other complications, including subarachnoid haemorrhage and lower extremity venous thrombosis. The patient was finally extubated on day 7, and haemodialysis was discontinued on day 42, with a daily urine output of approximately 2000 mL. The patient was discharged from the ICU 43 days after admission. Treatment and care activities under qualified nursing care, including managing haemorrhage and anticoagulation in haemodialysis, pain care based on psychological support, early rehabilitation and nutrition and providing appropriate care for respiratory support, contributed to the successful discharge of the patient from the ICU. During the patient's 43-day stay in the ICU, strict monitoring and personalized nursing care were implemented.

Efficacy and safety of margetuximab plus chemotherapy vs. trastuzumab plus chemotherapy in Chinese patients with pretreated HER2-positive advanced metastatic breast cancer: results from a randomized, open-label, multicenter, phase II bridging study.

Background: Trastuzumab is the recommended first-line treatment for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) patients in China, but therapeutic resistance to trastuzumab and other early-line treatments is common and late-line treatment options are limited. Derived from the same murine precursor antibody, margetuximab has enhanced anti-tumor activity compared with trastuzumab and may be an effective late-line treatment. However, data regarding the use of margetuximab in pre-treated Chinese patients are scarce. This study aimed to evaluate the efficacy and safety of margetuximab plus chemotherapy vs. trastuzumab plus chemotherapy in Chinese patients, and to determine whether the results are consistent with the clinical benefit of margetuximab observed in the pivotal global phase III study. Methods: In this randomized, open-label, multicenter, phase II bridging study, eligible Chinese patients pretreated with ≥2 lines of anti-HER2 therapies were randomized 1:1 by stratified block randomization to margetuximab (15 mg/kg over at least 120 minutes) or trastuzumab (6 mg/kg over at least 30 minutes), each administered intravenously once every 21-day cycle and plus chemotherapy. Disease assessment was conducted once every two treatment cycles (6 weeks ± 7 days). The primary endpoint was progression-free survival (PFS) by blinded independent central review (BICR). Secondary endpoints included overall survival (OS), investigator-assessed PFS, objective response rate (ORR), duration of response (DoR), clinical benefit rate (CBR), and the incidence and severity of treatment-emergent adverse events (TEAEs). Results: Between February 4, 2020 and February 23, 2021, 123 patients were randomized to the margetuximab (n=62) and trastuzumab (n=61) arms. Among them, 15 and 7 patients, respectively, were still on study treatment as of data cut-off (September 3, 2021). Overall, 99.2% were female, median age was 53 years old. All patients were pretreated with trastuzumab, and 83.7% and 25.2%, respectively, were pretreated with tyrosine kinase inhibitors (TKIs) and pertuzumab. Baseline characteristics were numerically balanced between arms. BICR-assessed median PFS (mPFS) was 5.5 months in the margetuximab arm and 4.1 months in the trastuzumab arm, with a hazard ratio (HR) of 0.69 [95% confidence interval (CI): 0.43-1.12], which met the consistency criterion (HR <0.88) for bridging success. Median investigator-assessed PFS was 5.5 months in the margetuximab arm and 4.0 months in the trastuzumab arm (HR =0.63; 95% CI: 0.41-0.96). Median OS (mOS) was not yet reached. Both ORR and CBR were greater in the margetuximab arm (25.5% vs. 12.5%; 32.7% vs. 14.3%). Safety results were numerically comparable between the two arms. Anti-HER2 treatment-related infusion-related reactions (IRRs) were more common in the margetuximab arm than in the trastuzumab arm (12.9% vs. 1.7%). All IRRs could be resolved. Conclusions: Margetuximab was effective and well-tolerated in this study, supporting its clinical use in pretreated HER2-positive MBC patients in China. Trial Registration: ClinicalTrials.gov Identifier: NCT04262804.

Functional reciprocity of proteins involved in mitosis and endocytosis.

Mitosis and endocytosis are two fundamental cellular processes essential for maintaining a eukaryotic life. Mitosis partitions duplicated chromatin enveloped in the nuclear membrane into two new cells, whereas endocytosis takes in extracellular substances through membrane invagination. These two processes are spatiotemporally separated and seemingly unrelated. However, recent studies have uncovered that endocytic proteins have moonlighting functions in mitosis, and mitotic complexes manifest additional roles in endocytosis. In this review, we summarize important proteins or protein complexes that participate in both processes, compare their mechanism of action, and discuss the rationale behind this multifunctionality. We also speculate on the possible origin of the functional reciprocity from an evolutionary perspective.

Graphene-bridged topological network metamaterials with perfect modulation applied to dynamic cloaking and meta-sensing.

Perfect state transfer of the bus topological system enables the sharing of information or excitation between nodes. Herein we report groundbreaking research on the transfer of the graphene-bridged bus topological network structure to an electromagnetic metamaterial setting, named "bus topological network metamaterials (TNMMs)." Correspondingly, the electromagnetic response imprints onto the topological excitation. We find that the bus-TNMMs display a perfect modulation of the terahertz response. The blue-shift of resonance frequency could increase to as large as 1075 GHz. The modulation sensitivity of the bus-TNMMs reaches 1027 GHz/Fermi level unit (FLU). Meanwhile, with the enhancement of modulation, the line shape of the reflection keeps underformed. Parabola, ExpDec1, and Asymptotic models are used to estimate the modulation of the resonance frequency. Besides, the bus-TNMMs system provides a fascinating platform for dynamic cloaking. By governing the Fermi level of graphene, the bus-TNMMs can decide whether it is cloaking or not in a bandwidth of 500 GHz. Also, the bus-TNMMs exhibit the immense potential for dynamically detecting the vibrational fingerprinting of an analyte. These results give a far-reaching outlook for steering dynamically the terahertz response with the bus-TNMMs. Therefore, we believe that the discovery of bus-TNMMs will revolutionize our understanding of the modulation of the electromagnetic response.