Gap design to enable functionalities into nested antiresonant nodeless fiber based systems.

By modifying the interconnection design between standard single-mode fiber (SSMF) and nested antiresonant nodeless type hollow-core fiber (NANF), we create an air gap between SSMF and NANF. This air gap enables the insertion of optical elements, thus providing additional functions. We show low-loss coupling using various graded-index multimode fibers acting as mode-field adapters resulting in different air-gap distances. Finally, we test the gap functionality by inserting a thin glass sheet in the air gap, which forms a Fabry-Perot interferometer and works as a filter with an overall insertion loss of only 0.31 dB.

Sequential high-intensity focused ultrasound treatment combined with chemotherapy for inoperable pancreatic cancer: a retrospective analysis for prognostic factors and survival outcomes.

OBJECTIVE: To evaluate the effect of HIFU (High-Intensity Focused Ultrasound) therapy on the survival and prognosis of patients with inoperable pancreatic cancer, and the clinical application of serological prognostic indicators. METHODS: We retrospectively analyzed the clinicopathological features, laboratory tests and follow-ups of 192 patients. Among the patients, 57 were treated with HIFU prior to chemotherapy (HIFU-priority), and 135 patients received chemotherapy followed by HIFU (HIFU-second). Univariate and multivariate Cox regression analysis was used to determine the prognostic value of tumor inflammation-related serological markers. A nomogram model was established based on the identified prognostic factors. RESULTS: Univariate analysis showed that receiving the treatment regimen in HIFU-priority was a significant protective factor for overall survival (OS, p < 0.001). Tumor stage, high C-reactive protein (CRP), high gamma-glutamyl transferase(γGT) high carbohydrate antigen 125 (CA125), high neutrophil-to-lymphocyte ratio (NLR), high lymphocyte-to-monocyte ratio (LMR) and liver metastasis were significant risk factors for poor prognosis (p < 0.05). CRP combined with normal tumor marker CA125 (CRP + CA125) was associated with longer OS (p = 0.005). Multivariate analysis shows that HIFU-priority is a protective factor for OS (Hazard Ratio, HR: 0.38; 95% confidence interval(CI): 0.25-0.57), tumor stage (HR: 1.61; 95% CI: 1.12-2.31), CRP + CA125 (HR: 1.46; 95% CI: 1.02-2.08) and γGT (HR: 1.44; 95% CI: 1.04-1.98) are risk factors for OS and serve as independent prognostic factors in the nomogram. CONCLUSION: Early application of HIFU treatment improves the OS of patients with inoperable pancreatic cancer. CRP + CA125 and γGT are independent prognostic factors.

COPS5 Conferred the Platinum Resistance in Epithelial Ovarian Cancer.

Development of platinum resistance is one of the major causes of epithelial ovarian cancer (EOC) treatment failure. COP9 signalosome subunit 5 (COPS5) was found to take part in the progression of EOC in our previous study. Herein, we aim to uncover the potential utility of COPS5 in EOC chemoresistance. COPS5 levels were analyzed to define clinic pathologic correlates using a matched tissue microarray and online datasets. The effect of COPS5 inhibition by the lentivirus-mediated short hairpin RNA on cell viability, proliferation and migration was accessed in vitro and in vivo. Results showed that COPS5 was upregulated in patients after platinum resistance. Kaplan-Meier survival curves revealed that COPS5 overexpression was correlated with shorter PFS and OS. COPS5 downregulation inhibited the cell proliferation, migration, and reduced the sensitivity of EOC to platinum. Overall, our data indicated that COPS5 inhibition might represent a new therapeutic strategy for overcoming platinum resistance in patients with EOC.

Low loss and broadband low back-reflection interconnection between a hollow-core and standard single-mode fiber.

We report simultaneous low coupling loss (below 0.2 dB at 1550 nm) and low back-reflection (below -60 dB in the 1200-1600 nm range) between a hollow core fiber and standard single mode optical fiber obtained through the combination of an angled interface and an anti-reflective coating. We perform experimental optimization of the interface angle to achieve the best combination of performance in terms of the coupling loss and back-reflection suppression. Furthermore, we examine parasitic cross-coupling to the higher-order modes and show that it does not degrade compared to the case of a flat interface, keeping it below -30 dB and below -20 dB for LP11 and LP02 modes, respectively.

Production, purification and characterization of a novel antithrombotic and anticoagulant serine protease from food grade microorganism Neurospora crassa.

A novel thrombolytic enzyme was produced by food grade microorganism Neurospora crassa using agro-industrial by-products as substrates. Process parameters were optimized using Plackett-Berman and Box-Benhken design. Under the optimized fermentation conditions, high fibrinolytic activity of 403.59 U/mL was obtained. It was purified with a specific activity of 3572.4 U/mg by ammonium sulfate precipitation and SP Sepharose chromatography. The molecular weight of the enzyme was approximately 32 kDa. It exhibited maximum activity at 40 °C and pH 7.4. Its activity was enhanced by Cu2+, Na+, Zn2+, and completely inhibited by phenylmethanesulfonyl fluoride, soybean trypsin inhibitor, aprotinin, which indicates it could be a serine protease. The enzyme could degrade fibrin clot directly without the need of plasminogen activator, and effectively cleaved Aα, Bß, γ chains of fibrinogen. It could inhibit the formation of blood clots in vitro and acts as an anticoagulant. Compared to heparin the purified enzyme showed extended anticoagulant activity. Blood clots were dissolved effectively and dissolution rate was increased with time. Based on these results, this novel enzyme has the potential to be developed as a thrombolytic agent.

Preamble Design and Collision Resolution in a Massive Access IoT System.

How to support massive access efficiently is one of the challenges in the future Internet of Things (IoT) systems. To address such challenge, this paper proposes an effective preamble collision resolution scheme to sustain massive random access (RA) for an IoT system. Specifically, a new sub-preamble structure is first proposed to reduce the preamble collision probability. To identify different devices that send the same preamble to the gNB on the same physical random access channel (PRACH), a multiple timing advance (TA) capturing scheme is then proposed. Thereafter, an RA scheme is designed to sustain massive access and the performance of the scheme is studied analytically. Finally, the effectiveness of the proposed RA scheme is validated by extensive simulation experiments in terms of preamble detection probability, preamble collision probability, RA success probability, resource efficiency and TA capturing.

Stochastic Latency Guarantee in Wireless Powered Virtualized Sensor Networks.

How to guarantee the data rate and latency requirement for an application with limited energy is an open issue in wireless virtualized sensor networks. In this paper, we integrate the wireless energy transfer technology into the wireless virtualized sensor network and focus on the stochastic performance guarantee. Firstly, a joint task and resource allocation optimization problem are formulated. In order to characterize the stochastic latency of data transmission, effective capacity theory is resorted to study the relationship between network latency violation probability and the transmission capability of each node. The performance under the FDMA mode and that under the TDMA mode are first proved to be identical. We then propose a bisection search approach to ascertain the optimal task allocation with the objective to minimize the application latency violation probability. Furthermore, a one-dimensional searching scheme is proposed to find out the optimal energy harvesting time in each time block. The effectiveness of the proposed scheme is finally validated by extensive numerical simulations. Particularly, the proposed scheme is able to lower the latency violation probability by 11.6 times and 4600 times while comparing with the proportional task allocation scheme and the equal task allocation scheme, respectively.

Targeting TPX2 suppresses proliferation and promotes apoptosis via repression of the PI3k/AKT/P21 signaling pathway and activation of p53 pathway in breast cancer.

Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated protein required for mitosis and spindle assembly. Previous studies showed that TPX2 is overexpressed in various human cancers and promotes cancer progression. In this study, the differentially expressed genes including TPX2 were screened in GEO database for gene expression microarray of breast cancer. The TPX2 expression level was significantly increased in breast cancer cells and the breast malignant tissues compared with those controls. In vitro experiment further confirmed that knockdown of TPX2 by small hairpin RNA inhibited breast cancer cell proliferatio, migration, and induced cell apoptosis. TPX2 silencing decreased the expression of PI3K and extent of AKT phosphorylation, as well as increased expression of p53 and p21. Taken together, our findings indicate that TPX2 silencing negatively regulates the PI3K/AKT and activates p53 signaling pathway by which breast cancer cells proliferation were inhibited whereas cellulars apoptosis were accelerated, suggesting that TPX2 may be a potential target for anticancer therapy in breast cancer.

Establishment of a detection assay for DNA endonuclease activity and its application in the screening and prognosis of malignant lymphoma.

BACKGROUND: Endonucleases play critical roles in maintaining genomic stability and regulating cell growth. The purpose of this study was to evaluate detection of endonuclease activity as an indicator in the early diagnosis and prognosis of lymphoma. RESULTS: The method of endonuclease activity determination was successfully established and applied to compare cancer patient and control cohorts. Endonuclease activities of cancer tissues were significantly higher than those of adjacent control tissues (P < 0.001). We next investigated endonuclease activity in peripheral blood of enrolled patients and the controls, which were also significantly higher in patients than in controls (P = 0.015). Additionally, endonuclease activities were elevated in the metastasis subgroup compared with the non-metastasis subgroup(P = 0.038), whereas no significant difference was found between age(≤ 56y, > 56y) and gender (P = 0.736 > 0.05 and P = 0.635 > 0.05, respectively). Although there was no significant difference between control group with the non-metastatic cancer patients (P = 0.800 > 0.05), endonuclease activities were lower in the control group compared with the non-metastatic cancer patients with lymphoma (P = 0.033). The progression-free survival probability of patients with elevated R ratios(R ratio ≥ 1.4) was significantly lower than that of patients with lower R ratios (R ratio < 1.4). CONCLUSIONS: An assay was established to detect the endonuclease activity,which might be useful for the prognosis of cancers, especially lymphoma.

COPS5 inhibition arrests the proliferation and growth of serous ovarian cancer cells via the elevation of p27 level.

The fifth component of the COP9 signalosome complex (COPS5), which plays an essential role in ubiquitin-mediated protein degradation, has been found as a prognostic biomarker for multiple cancers, however, the role of COPS5 in serous ovarian cancer (SOC) remain to be clarified. In this study, we found that COPS5 expression was significantly increased in SOC cells and tissues compared with those controls. Mechanistically, COPS5 and p27was proved to interact with each other, with COPS5 acts as a negative regulator of p27. SOC cells with COPS5 depletion were arrested in G1/G0-phase and exhibited a reduced proliferation ability and an increased cytoplasmic p27 expression. Whereas, the cells were stuck at S-phase accompanied with an elevation of nucleus p27 expression after knocking down COPS6 or blocking COPS5 by CSN5i-3. Furthermore, inhibition of COPS5 resulted in an elevation of Akt expression and sensitized SOC cells to Akt inhibitor MK2206. Suppression of COPS5 and Akt offers a potential strategy for the treatment of SOC.

[Role of TRPV4 channels in regulation of eNOS expression in brain microvascular endothelial cells under the condition of mechanical stretch].

OBJECTIVE: To identify the subtype of transient receptor potential (TRPs) channel involved in stretch-induced injury of human brain microvascular endothelial cells (HBMEC) and to explore the mechanism responsible for eNOS expression.
 METHODS: TRPs expression was examined by Western blot and immunocytofluoresence in the cultured HBMEC. Mechanical stretch was performed by mini-type multi-functional bio-impact machine. The levels of free calcium ion in cells were examined by the flow cytometry. The eNOS expression was detected by Western blot.
 RESULTS: The mRNA and protein expression of TRPV4 was detected in HBMEC by qRT-PCR, Western blot and immunocytofluoresence. The levels of free calcium ion in the stretch-treated HBMEC was significantly decreased in the presence of TRPV4 specific inhibitor (P<0.001), but there was no difference in calcium levels between the stretch and the control or unspecific inhibitor group (P=0.072 or 0.308). The levels of eNOS protein in the stretch-treated HBMEC were reduced in the presence of TRPV4 specific inhibitor or NOS inhibitor (P<0.05), but it was not changed compared with that in the control group (P>0.05).
 CONCLUSION: The eNOS expression is up-regulated under the condition of mechanic stretch, which is related to the activation of TRPV4, resulting in the influx of calcium.

Suppression of NBS1 Upregulates CyclinB to Induce Olaparib Sensitivity in Ovarian Cancer.

Background: Deficiencies in DNA damage repair responses promote chemotherapy sensitivity of tumor cells. The Nibrin homolog encoding gene Nijmegen Breakage Syndrome 1 (NBS1) is a crucial component of the MRE11-RAD50-NBN complex (MRN complex) and is involved in the response to DNA double-strand breaks (DSBs) repair that has emerged as an attractive strategy to overcome tumor drug resistance, but the functional relationship between NBS1 regulated DNA damage repair and cell cycle checkpoints has not been fully elucidated. Methods: In this study, lentivirus-mediated RNAi was used to construct NBS1-downregulated cells. Flow cytometry, qPCR, and immunohistochemistry were used to explore the regulatory relationship between NBS1 and CyclinB in vivo and in vitro. Results: Our findings suggest that NBS1 deficiency leads to defective homologous recombination repair. Inhibition of NBS1 expression activates CHK1 and CyclinB signaling pathways leading to cell cycle arrest and sensitizes ovarian cancer cells to Olaparib treatment in vitro and in vivo. NBS1-deficient ovarian cancer cells tend to maintain sensitivity to chemotherapeutic drugs through activation of cell cycle checkpoints. Conclusions: NBS1 may be a potential therapeutic target for epithelial ovarian cancer as it plays a role in the regulation of the DNA damage response and cell cycle checkpoints. Suppression of NBS1 upregulates CyclinB to induce Olaparib sensitivity in ovarian cancer.

Risk factors of aspiration occurrence with different feeding patterns in elderly intensive care unit patients: a cross-sectional study.

Background: Elderly intensive care unit (ICU) patients represent a high-risk group of aspiration. Different feeding patterns will lead to different incidences of aspiration. However, there are few studies on the risk factors of aspiration in elderly ICU patients under different feeding patterns. The aim of this study was to analyze the effects of different eating styles on the occurrence of overt and silent aspiration in elderly ICU patients and to compare the independent risk factors, in order to provide a basis for targeted aspiration prevention. Methods: We retrospectively analyzed the incidence of aspiration in elderly patients admitted to the ICU from April 2019 to April 2022, a total of 348 cases. The patients were divided into the oral feeding group, gastric tube feeding group, and post-pyloric feeding group according to their feeding method. Multi-factor logistic regression was used to analyze the independent risk factors for overt and silent aspiration caused by the different eating patterns of patients. Results: Among the 348 elderly ICU patients included, the overall incidence of aspiration was 72%, with a 22% rate of overt aspiration and a 49% rate of silent aspiration. The overt aspiration rates were 16%, 30%, and 21% in the oral, the gastric tube and the post-pyloric feeding group, respectively; while the silent aspiration rates were 52%, 55%, and 40% in the three groups, respectively. Multiple logistic regression analysis showed that the independent risk factors for both overt and silent aspiration were history of aspiration [odds ratio (OR) =0.075, P=0.004; OR =0.205, P=0.042] and gastrointestinal tumor (OR =0.100, P=0.028; OR =0.063, P=0.003) in the oral feeding group. In the gastric tube feeding group, the independent risk factor for both overt and silent aspiration was the history of aspiration (OR =4.038, P=0.040; OR =4.658, P=0.012). In the post-pyloric feeding group, the independent risk factors for both overt and silent aspiration were mechanical ventilation (OR =0.211, P=0.019; OR =0.336, P=0.037) and intra-abdominal hypertension (OR =0.225, P=0.020; OR =0.329, P=0.032). Conclusions: There were significant differences in the influencing factors and characteristics of aspiration among the elderly patients in the ICU with different feeding patterns. Personalized precautions should be implemented early, so as to reduce the possibility of aspiration.

Lung Transplantation for Pulmonary Arterial Hypertension: Optimized Referral and Listing Based on an Evolving Disease Concept.

Pulmonary hypertension (PH) was once a devastating and fatal disease entity, the outlook of which has been significantly improved by the continued progress of medical treatment algorithms. However, some patients still ultimately fail to achieve an adequate clinical response despite receiving maximal medical treatment. Historically, lung transplantation (LTx) has been the only effective therapeutic option that could lead to satisfactory outcomes and save these advanced patients' lives. However, patients with PH tend to have the highest mortality rates on the transplant waiting list; especially after comprehensive medical treatment, they continue to deteriorate very rapidly, eventually missing optimal transplantation windows. Balancing optimized medical treatment with the appropriate timing of referral and listing has been highly controversial in LTx for patients with PH. The 2021 consensus document for the selection of lung transplant candidates from the International Society for Heart and Lung Transplantation (ISHLT) updated the specific recommendations for the LTx referral and listing time for patients with PH based on objective risk stratification. Herein, we review the evolving PH-related concepts and highlight the optimization of LTx referral and listing for patients with PH, as well as their management on the waiting list.

A New Type of Endometrial Cancer Models in Mice Revealing the Functional Roles of Genetic Drivers and Exploring their Susceptibilities.

Endometrial cancer (EC) is the most common female reproductive tract cancer and its incidence has been continuously increasing in recent years. The underlying mechanisms of EC tumorigenesis remain unclear, and efficient target therapies are lacking, for both of which feasible endometrial cancer animal models are essential but currently limited. Here, an organoid and genome editing-based strategy to generate primary, orthotopic, and driver-defined ECs in mice is reported. These models faithfully recapitulate the molecular and pathohistological characteristics of human diseases. The authors names these models and similar models for other cancers as organoid-initiated precision cancer models (OPCMs). Importantly, this approach can conveniently introduce any driver mutation or a combination of driver mutations. Using these models,it is shown that the mutations in Pik3ca and Pik3r1 cooperate with Pten loss to promote endometrial adenocarcinoma in mice. In contrast, the Kras G12D mutati led to endometrial squamous cell carcinoma. Then, tumor organoids are derived from these mouse EC models and performed high-throughput drug screening and validation. The results reveal distinct vulnerabilities of ECs with different mutations. Taken together, this study develops a multiplexing approach to model EC in mice and demonstrates its value for understanding the pathology of and exploring the potential treatments for this malignancy.

KMT2D Deficiency Promotes Myeloid Leukemias which Is Vulnerable to Ribosome Biogenesis Inhibition.

KMT2C and KMT2D are the most frequently mutated epigenetic genes in human cancers. While KMT2C is identified as a tumor suppressor in acute myeloid leukemia (AML), the role of KMT2D remains unclear in this disease, though its loss promotes B cell lymphoma and various solid cancers. Here, it is reported that KMT2D is downregulated or mutated in AML and its deficiency, through shRNA knockdown or CRISPR/Cas9 editing, accelerates leukemogenesis in mice. Hematopoietic stem and progenitor cells and AML cells with Kmt2d loss have significantly enhanced ribosome biogenesis and consistently, enlarged nucleolus, increased rRNA and protein synthesis rates. Mechanistically, it is found that KMT2D deficiency leads to the activation of the mTOR pathway in both mouse and human AML cells. Kmt2d directly regulates the expression of Ddit4, a negative regulator of the mTOR pathway. Consistent with the abnormal ribosome biogenesis, it is shown that CX-5461, an inhibitor of RNA polymerase I, significantly restrains the growth of AML with Kmt2d loss in vivo and extends the survival of leukemic mice. These studies validate KMT2D as a de facto tumor suppressor in AML and reveal an unprecedented vulnerability to ribosome biogenesis inhibition.

Care Bundles plus Detailed Nursing on Mortality and Nursing Satisfaction of Patients with Septic Shock in ICU.

Objective: To evaluate the effect of care bundles combined with detailed nursing on the mortality and nursing satisfaction of patients with septic shock in the intensive care unit (ICU). Methods: Ninety patients with septic shock in the ICU admitted to our hospital from April 2019 to April 2020 were recruited and assigned to an experimental group and a control group via the random table method, with 45 cases in each group. The control group adopted conventional nursing, and the experimental group received care bundles combined with detailed nursing. The nursing effect, satisfaction, and mortality of the two groups were compared. The "Glasgow Coma Scale" (GCS) was used to evaluate the coma of the patients, the "Coma Recovery Scale" (CRS-R) was used to assess the state of consciousness of the patients, and the "Hospital Anxiety and Depression" (HAD) scale was used to evaluate the patient's emotional status before and after the intervention. Results: The experimental group showed a significantly higher nursing efficiency and better nursing satisfaction than the control group (P < 0.05). Lower mortality was found in the experimental group in contrast to the control group (P < 0.05). The experimental group had higher GCS scores and CRS-R scores and lower HAD scores than the control group (P < 0.05). Conclusion: Care bundles plus detailed nursing for patients with septic shock in the ICU improve the nursing effect and nursing satisfaction, reduce the mortality rate, and mitigate the clinical symptoms of patients, which shows great potential in clinical application and promotion.

A combined strategy of TK1, HE4 and CA125 shows better diagnostic performance than risk of ovarian malignancy algorithm (ROMA) in ovarian carcinoma.

BACKGROUND: The dual marker algorithm Risk of Ovarian Malignancy Algorithm (ROMA) has been widely used in the clinic for the identification of equivocal pelvic masses in ovarian carcinoma. To obtain higher diagnostic efficiency, we created a new diagnostic index, Risk of Ovarian Malignancy Index (ROMI), by combing thymidine kinase 1 (TK1), HE4 and CA125. METHODS: 335 patients with pelvic masses on imaging and 46 healthy controls were enrolled. Serum TK1 was analyzed before further study. ROMI and ROMA were evaluated for diagnostic efficiency. RESULTS: The level of TK1 was elevated in malignant ovarian tumors compared to benign masses (p < 0.001) and healthy controls (p < 0.001). TK1 expression was positively correlated with stage, intrapelvic metastasis, lymphatic metastasis and distant metastasis (all p values < 0.001). The area under the receiver operating characteristic curve (AUC) of ROMI was higher than that of ROMA for both pre- and postmenopausal women. ROMI had better sensitivity, specificity, accuracy, and positive and negative predictive values than ROMA in diagnosis of all-stage or stage I + II ovarian carcinoma for both pre- and postmenopausal women. CONCLUSIONS: TK1 is a potential biomarker in detection of ovarian carcinoma. ROMI shows better diagnostic performance than ROMA in distinguishing malignant ovarian tumors from benign masses.

Fabrication of alkali lignin-based emulsion electrospun nanofibers for the nanoencapsulation of beta-carotene and the enhanced antioxidant property.

For the greater utilization of ß-carotene in antioxidant material, ß-carotene-loaded emulsion stabilized by alkali lignin (AL) was successfully electrospinning with poly (vinyl alcohol) (PVA) (PVA/AL/ß-carotene nanofiber). Transmission electron microscopy demonstrated the core-shell structure of nanofiber with the average diameter being 356.31 nm, and 85.7 % of ß-carotene was effectively encapsulated into the core section. Fourier transform infrared spectra and differential scanning calorimetry revealed the good compatibility and decreased crystallinity of ß-carotene, favoring its stability and solubility, respectively. As expected, the PVA/AL/ß-carotene nanofiber exhibited higher antioxidant activity than free ß-carotene due to the protection of AL matrix and the special structure of nanofiber, as the DPPH free radical scavenging rate being 90.7 % at 7th day. The sustained release behavior of ß-carotene and AL from fiber followed Fickian diffusion model, contributing to the greater protection for fish oil than that of emulsion. Thus, this study provides an approach to develop hydrophobic compounds-loaded emulsion electrospun antioxidant material with controlled release property and enhanced activity.

Tripterin liposome relieves severe acute respiratory syndrome as a potent COVID-19 treatment.

For coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 15-30% of patients are likely to develop COVID-19-related acute respiratory distress syndrome (ARDS). There are still few effective and well-understood therapies available. Novel variants and short-lasting immunity are posing challenges to vaccine efficacy, so finding antiviral and antiinflammatory treatments remains crucial. Here, tripterin (TP), a traditional Chinese medicine, was encapsulated into liposome (TP lipo) to investigate its antiviral and antiinflammatory effects in severe COVID-19. By using two severe COVID-19 models in human ACE2-transgenic (hACE2) mice, an analysis of TP lipo's effects on pulmonary immune responses was conducted. Pulmonary pathological alterations and viral burden were reduced by TP lipo treatment. TP lipo inhibits SARS-CoV-2 replication and hyperinflammation in infected cells and mice, two crucial events in severe COVID-19 pathophysiology, it is a promising drug candidate to treat SARS-CoV-2-induced ARDS.