Smooth Muscle Cell-Specific LKB1 Protects Against Sugen5416/Hypoxia-Induced Pulmonary Hypertension through Inhibition of BMP4.

Pulmonary hypertension (PH) is a life-threatening syndrome associated with hyperproliferation of pulmonary artery smooth muscle cells (PASMCs), which exhibit similar features to cancer cells. Currently, there is no curative treatment for PH. LKB1 is known as a tumor suppressor gene with an anti-proliferative effect on cancer cells. However, its role and mechanism in the development of PH remain unclear. Gain-and loss-of-function strategies were used to elucidate the mechanisms of LKB1 in regulating the occurrence and progression of PH. Sugen5416/Hypoxia (SuHx) PH model was utilized for in vivo study. We observed not only a decreased expression of LKB1 in the lung vessels of the SuHx mouse model, but also in human pulmonary artery smooth muscle cells (HPASMCs) exposed to hypoxia. Smooth muscle-specific LKB1 knockout significantly aggravated SuHx-induced PH in mice. RNA sequencing analysis revealed a substantial increase in bone morphogenetic protein-4 (BMP4) in the aortas of LKB1SMKO mice compared with controls, identifying BMP4 as a novel target of LKB1. LKB1 knockdown in HPASMCs cultured under hypoxic conditions increased BMP4 protein level and HPASMC proliferation and migration. The co-immunoprecipitation analysis revealed that LKB1 directly modulates BMP4 protein degradation through phosphorylation. Therapeutically, suppressing BMP4 expression in SMCs alleviates PH in LKB1SMKO mice. Our findings demonstrate that LKB1 attenuates PH by enhancing the lysosomal degradation of BMP4, thus suppressing the proliferation and migration of HPASMCs. Modulating LKB1-BMP4 axis in SMC could be a promising therapeutic strategy of PH.

Computed tomography-guided radioactive iodine-125 seed implantation for liver malignancies in challenging locations.

AIMS: This study aimed to retrospectively assess the safety and efficacy of radioactive iodine-125 (I-125) seed implantation for liver malignancies in challenging locations. MATERIALS AND METHODS: Between December 2015 and December 2021, 49 patients with 60 liver malignancies in challenging locations who underwent computed tomography (CT)-guided I-125 seed implantation were retrospectively analyzed. The primary endpoints included technical success rate and overall survival (OS), whereas the secondary endpoints included progression-free survival (PFS), disease control rate (DCR), objective response rate (ORR), and liver recurrence. Potential factors associated with liver recurrence were also evaluated. RESULTS: The technical success rate was 100%. The median follow-up duration was 12 months (range, 2-68 months). The mean OS and PFS were 17.58 months (95% CI: 13.64-21.52 months) and 13.14 months (95% CI: 10.36-15.92 months), respectively. The 2-month, 6-month, and 1-year DCR and ORR were 97.96% and 93.88%, 93.75% and 77.08%, and 93.48% and 60.87%, respectively. The 6- and 12-month tumor recurrence rates were 20.41% and 28.26%, respectively. The Kaplan-Meier method was used to estimate the time of liver recurrence, with our results showing that patients with primary intrahepatic cholangiocarcinoma had an increased likelihood of having earlier liver recurrence. No major complications developed during follow-up. CONCLUSION: CT-guided radioactive I-125 implantation could be a safe and effective alternative with promising survival benefits and high local control rates for liver malignancies in challenging locations.

Stereotactic ablative brachytherapy versus percutaneous microwave ablation as salvage treatments for lung oligometastasis from colorectal cancer.

BACKGROUND: The treatment for lung oligometastasis from colorectal cancer (CRC) remains challenging. This retrospective study aimed to compare the local tumor control, survival and procedure-related complications in CRC patients undergoing low-dose rate stereotactic ablative brachytherapy (L-SABT) versus percutaneous microwave ablation (MWA) for lung oligometastasis. METHODS: Patients between November 2017 and December 2020 were retrospectively analyzed. Local tumor progression-free survival (LTPFS) and overall survival (OS) were analyzed in the entire cohort as well as by stratified analysis based on the minimal ablation margin (MAM) around the tumor. RESULTS: The final analysis included 122 patients: 74 and 48 in the brachytherapy and MWA groups, respectively, with a median follow-up of 30.5 and 35.3 months. The 1- and 3-year LTPFS rate was 54.1% and 40.5% in the brachytherapy group versus 58.3% and 41.7% in the MWA group (P = 0.524 and 0.889, respectively). The 1- and 3-year OS rate was 75.7% and 48.6% versus 75.0% and 50.0% (P = 0.775 and 0.918, respectively). Neither LTPFS nor OS differed significantly between the patients with MAM of 5-10 mm versus > 10 mm. Pulmonary complication rate did not differ in the overall analysis, but was significantly higher in the MWA group in the subgroup analysis that only included patients with lesion within 10 mm from the key structures (P = 0.005). The increased complications was primarily bronchopleural fistula. CONCLUSIONS: Considering the caveats associated with radioisotope use in L-SABT, MWA is generally preferable. In patients with lesion within 10 mm from the key pulmonary structures, however, L-SABT could be considered as an alternative due to lower risk of bronchopleural fistula.

High-Energy SiO-Sulfur Battery with Preloaded Li3N in a Cathode as a Lithiation Reagent.

The practical use of lithium-sulfur batteries faces the "shuttle effect" and lithium dendrite growth. Employing SiO instead of Li metal can fundamentally solve the above problems. Nevertheless, selecting a convenient prelithiation method is essential for normal operation of the battery system. Hence, this work proposed a novel SiO-sulfur battery with preloaded Li3N in a cathode as a prelithiation reagent, which can thoroughly solve the dendrite problem and the side reaction with polysulfides of lithium anode. The S@KB-Li3N vs SiO full cell can obtain a high specific capacity of 790 mAh g-1 after the activation process and be maintained at 478 mAh g-1 after 100 cycles. Our design will provide a new prelithiation strategy for a high-specific-energy SiO-sulfur battery system.

Comparison of ethanol-soaked gelatin sponge and microspheres for hepatic arterioportal fistulas embolization in hepatic cellular carcinoma.

BACKGROUND: Hepatic arterioportal fistulas (APFs) are common in hepatocellular carcinoma (HCC). Moreover, correlated with poor prognosis, APFs often complicate anti-tumor treatments, including transarterial chemoembolization (TACE). AIM: To compare the efficacy of ethanol-soaked gelatin sponges (ESG) and microspheres in the management of APFs and their impact on the prognosis of HCC. METHODS: Data from patients diagnosed with HCC or hepatic APFs between June 2016 and December 2019 were retrospectively analyzed. Furthermore, APFs were embolized with ESG (group E) or microspheres (group M) during TACE. The primary outcomes were disease control rate (DCR) and objective response rate (ORR). The secondary outcomes included immediate and first follow-up APF improvement, overall survival (OS), and progression-free survival (PFS). RESULTS: Altogether, 91 participants were enrolled in the study, comprising 46 in group E and 45 in group M. The DCR was 93.5% and 91.1% in groups E and M, respectively (P = 0.714). The ORRs were 91.3% and 66.7% in groups E and M, respectively (P = 0.004). The APFs improved immediately after the procedure in 43 (93.5%) patients in group E and 40 (88.9%) patients in group M (P = 0.485). After 2 mo, APF improvement was achieved in 37 (80.4%) and 33 (73.3%) participants in groups E and M, respectively (P = 0.421). The OS was 26.2 ± 1.4 and 20.6 ± 1.1 mo in groups E and M, respectively (P = 0.004), whereas the PFS was 16.6 ± 1.0 and 13.8 ± 0.7 mo in groups E and M, respectively (P = 0.012). CONCLUSION: Compared with microspheres, ESG embolization demonstrated a higher ORR and longer OS and PFS in patients of HCC with hepatic APFs.

In-situ-grown multidimensional Cu-doped Co1-xS2@MoS2 on N-doped carbon nanofibers as anode materials for high-performance alkali metal ion batteries.

Transition metal sulfides with the high theoretical capacity and low cost have been considered as advanced anode candidate for alkali metal ion batteries, but suffered from unsatisfactory electrical conductivity and huge volume expansion. Herein, a multidimensional structure Cu-doped Co1-xS2@MoS2 in-situ-grown on N-doped carbon nanofibers (denoted as Cu-Co1-xS2@MoS2 NCNFs) have been elaborately constructed for the first time. The bimetallic zeolitic imidazolate framework CuCo-ZIFs were encapsulated in the one-dimensional (1D) NCNFs through an electrospinning route and then on which the two-dimensional (2D) MoS2 nanosheets were in-situ grown via a hydrothermal process. The architecture of 1D NCNFs can effectively shorten ion diffusion path and enhance electrical conductivity. Besides, the formed heterointerface between MOF-derived binary metal sulfides and MoS2 can provide extra active centers and accelerate reaction kinetics, which guarantee a superior reversibility. As expected, the resulting Cu-Co1-xS2@MoS2 NCNFs electrode delivers excellent specific capacity of Na-ion batteries (845.6 mAh/g at 0.1 A/g), Li-ion batteries (1145.7 mAh/g at 0.1 A/g), and K-ion batteries (474.3 mAh/g at 0.1 A/g). Therefore, this innovative design strategy will bring a meaningful prospect for developing high-performance multi-component metal sulfides electrode for alkali metal ion batteries.

The Relationship Between Perceptions of Leader Hypocrisy and Employees' Knowledge Hiding Behaviors: Testing a Moderated Mediation Model.

Purpose: Knowledge-sharing is critical for the survival and development of today's organization, but employees are not always willing to share their knowledge and sometimes even hide it intentionally or unintentionally. Taken from the leadership perspective, this paper aims to investigate the influence of leader hypocrisy on employees' knowledge-hiding behaviors. Drawing on the self-determination theory (SDT), this paper explores the mediating role of basic psychological needs satisfaction, as well as the moderating effect of employees' interdependent self-construal on the relationship between basic psychological needs satisfaction and knowledge-hiding behaviors. The moderated mediation effect is also tested. Methods: The data were collected from companies located in mainland China. The data sample for analysis consists of 336 employees. Hierarchical regression analysis was adopted to test the hypotheses of our proposed model. Results: Leader hypocrisy are positively related to knowledge-hiding behaviors (b = 0.490, p < 0.01). Basic psychological needs satisfaction plays a partial mediating role in such relationship (b =0.118, [0.056, 0.210]). The interdependent self-construal moderates the relationship between basic psychological needs satisfaction and knowledge-hiding behaviors (b = 0.134, p < 0.01), as well as the moderated mediation effect (BootSE = 0.018, [-0.083, -0.009]). Conclusion: The results show that leader hypocrisy is positively related to knowledge-hiding behaviors, and basic psychological needs satisfaction partially mediates such relationship. The interdependent self-construal weakens the negative relationship between basic psychological needs satisfaction and knowledge hiding.

Anti-HIV drug repurposing against SARS-CoV-2.

A novel severe acute respiratory syndrome human coronavirus (SARS HCoV) was identified from respiratory illness patients (named SARS-CoV-2 by ICTV) in December 2019 and has recently emerged as a serious threat to world public health. However, no approved drugs have been found to effectively inhibit the virus. Since it has been reported that HIV protease inhibitors can be used as anti-SARS drugs by targeting SARS-CoV-1 3CLpro, we chose six approved anti-HIV drugs and investigated their binding interactions with 3CLpro to evaluate their potential to become clinical drugs for the new coronavirus pneumonia (COVID-19) caused by SARS-CoV-2 infection. The molecular docking results indicate that the 3CLpro of SARS-CoV-2 has a higher binding affinity for all the studied inhibitors than does SARS-CoV-1. Two docking complexes (indinavir and darunavir) with high docking scores were further subjected to MM-PBSA binding free energy calculations to detail the molecular interactions between these two protease inhibitors and SARS HCoV 3CLpro. Our results show that, among the inhibitors tested, darunavir has the highest binding affinity with SARS-CoV-2 and SARS-CoV-1 3CLpro, indicating that it may have the potential to be used as an anti-COVID-19 clinical drug. The mechanism behind the increased binding affinity of HIV protease inhibitors toward SARS-CoV-2 3CLpro (as compared to SARS-CoV-1) was investigated by MD simulations. Our study provides insight into the possible role of structural flexibility during interactions between SARS HCoV 3CLpro and inhibitors and sheds light on structure-based design of anti-COVID-19 drugs targeting SARS-CoV-2 3CLpro.

[The Implementation of the Right to Equality in the Care of a Vulnerable Medical Population: Pregnant and Postpartum Lesbians].

Medical equality is a basic right for patients, and awareness of the need for friendly medical care is increasing alongside international trends of promoting gender equality. Whether clinical professionals are sufficiently enabled and motivated to maintain justice and protect their patients, especially those from vulnerable populations, is an issue that deserves greater attention. We examined the situation of pregnant and postpartum lesbian woman to assess the ethical abilities of clinical professionals. We reflect on whether these patients received appropriate medical care and treatment from the perspective of medical equality. To date, nursing education has placed significantly greater emphasis on protecting the autonomy of patients and on ethical decision-making abilities than on instituting medical equality. In clinical practice, the ethical responses of clinical professionals to equality directly impact vulnerable populations. How clinicians collect clinical data and judge individual cases may cause patients to feel neglected. To carry out friendly medical care effectively, steps must be taken to improve the quality of care. As clinical professionals provide medical treatment, they should be more empathetic toward lesbian postpartum women, maintain an attitude of equality, and refrain from judging the sexual tendencies of individual cases, and protect the privacy of their patients. Regarding the special needs of vulnerable populations, clinical professionals should continue learning and spending time reflecting on methods to improve quality of care.

A Highly Selective Turn-on and Reversible Fluorescent Chemosensor for Al3+ Detection Based on Novel Salicylidene Schiff Base-Terminated PEG in Pure Aqueous Solution.

The development of highly selective and sensitive chemosensors for Al3+ detection in pure aqueous solution is still a significant challenge. In this work, a novel water-soluble polymer PEGBAB based on salicylidene Schiff base has been designed and synthesized as a turn-on fluorescent chemosensor for the detection of Al3+ in 100% aqueous solution. PEGBAB exhibited high sensitivity and selectivity to Al3+ over other competitive metal ions with the detection limit as low as 4.05 × 10-9 M. PEGBAB displayed high selectivity to Al3+ in the pH range of 5⁻10. The fluorescence response of PEGBAB to Al3+ was reversible in the presence of ethylenediaminetetraacetic acid (EDTA). Based on the fluorescence response, an INHIBIT logic gate was constructed with Al3+ and EDTA as two inputs. Moreover, test strips based on PEGBAB were fabricated facilely for convenient on-site detection of Al3+.