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Immunohistochemistry (IHC) using fluorescent probes provides high resolution with multiplexing capability, but the imaging contrast is limited by the brightness of the fluorescent probe and the intrinsic autofluorescence background from tissues. Herein, we improved the contrast by high-density labeling of long-lifetime lanthanide complexes and time-gated imaging. As the large (∼280 nm) Stokes shift of lanthanide complexes effectively prevents the issue of concentration quenching, we succeeded in conjugating seven europium complexes to an eight-arm hydrophilic poly(ethylene glycol) (PEG) linker for signal amplification with improved water solubility to the level of up to 10 mg/mL. Moreover, we demonstrated that both human epidermal growth factor receptor 2 (HER2) in a formalin-fixed paraffin-embedded (FFPE) tissue section and cytokeratin 18 (CK18) in a frozen section can be resolved with the enhanced contrast by 2-fold and 3-fold, respectively. Furthermore, we show that the PEGylation of multiple lanthanide complexes is compatible with tyramide signal amplification (TSA). This work suggests new opportunities for sensitive imaging of low-abundance biomarkers in a tissue matrix.

Approximately 10% of monogenic diseases are caused by nonsense point mutations that generate premature termination codons (PTCs), resulting in a truncated protein and nonsense-mediated decay of the mutant mRNAs. Here, we demonstrate a mini-dCas13X-mediated RNA adenine base editing (mxABE) strategy to treat nonsense mutation-related monogenic diseases via A-to-G editing in a genetically humanized mouse model of Duchenne muscular dystrophy (DMD). Initially, we identified a nonsense point mutation (c.4174CT, p.Gln1392*) in the DMD gene of a patient and validated its pathogenicity in humanized mice. In this model, single adeno-associated virus (AAV)-packaged mxABE reached A-to-G editing rates up to 84% in vivo, which is at least 20-fold greater compared to rates reported in previous studies using other RNA-editing modalities. Furthermore, mxABE restored robust expression of dystrophin protein to over 50% of wild-type (WT) levels by enabling PTC read-through in multiple muscle tissues. Importantly, systemic delivery of mxABE by AAV also rescued dystrophin expression to averages of 37%, 6%, and 54% of WT levels in the diaphragm, tibialis anterior, and heart muscle, respectively, as well as rescued muscle function. Our data strongly suggest that mxABE-based strategies may be a viable new treatment modality for DMD and other monogenic diseases.

Background The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads rapidly and insidiously. Coronavirus disease 2019 (COVID-19) screening is an important means of blocking community transmission in China, but the costs associated with testing are high. Quarantine capacity and medical resources are also threatened. Therefore, we aimed to evaluate different screening strategies to balance outbreak control and consumption of resources. Methods A community network of 2000 people, considering the heterogeneities of household size and age structure, was generated to reflect real contact networks, and a stochastic individual-based dynamic model was used to simulate SARS-CoV-2 transmission and assess different whole-area nucleic acid screening strategies. We designed a total of 87 screening strategies with different sampling methods, frequencies of screening, and timings of screening. The performance of these strategies was comprehensively evaluated by comparing the cumulative infection rates, the number of tests, and the quarantine capacity and consumption of medical resource, which were expressed as medians (95% uncertainty intervals, 95% UIs). Results To implement COVID-19 nucleic acid testing for all people (Full Screening), if the screening frequency was four times/week, the cumulative infection rate could be reduced to 13% (95% UI: 1%, 51%), the miss rate decreased to 2% (95% UI: 0%, 22%), and the quarantine and medical resource consumption was lower than higher-frequency Full Screening or sampling screening. When the frequency of Full Screening increased from five to seven times/week (which resulted in a 2581 increase in the number of tests per positive case), the cumulative infection rate was only reduced by 2%. Screening all people weekly by splitting them equally into seven batches could reduce infection rates by 73% compared to once per week, which was similar to Full Screening four times/week. Full Screening had the highest number of tests per positive case, while the miss rate, number of tests per positive case, and hotel quarantine resource consumption in Household-based Sampling Screening scenarios were lower than Random Sampling Screening. The cumulative infection rate of Household-based Sampling Screening or Random Sampling Screening seven times/week was similar to that of Full Screening four times/week. Conclusions If hotel quarantine, hospital and shelter hospital capacity are seriously insufficient, to stop the spread of the virus as early as possible, high-frequency Full Screening would be necessary, but intermediate testing frequency may be more cost-effective in non-extreme situations. Screening in batches is recommended if the testing capacity is low. Household-based Sampling Screening is potentially a promising strategy to implement. Graphical Abstract

The Omicron variant has become the dominant COVID-19 variant worldwide due to its rapid and cryptic spread; therefore, successful early warning is of great importance to be able to control epidemics in their early phase, before developing into large outbreaks. COVID-19-related Baidu search index, which reflects human behavior to a certain degree, was used to retrospectively detect the warning signs for Omicron variant outbreaks in China in 2022. The characteristics and effects of warning signs were analyzed in detail. We detected the presence of early warning signs (both high and low thresholds) and found that these occurred 4-7 days earlier than traditional epidemiological surveillance and20 days earlier than the implementation of the local "lockdown" policy. Compared with the "high threshold" warning, the early warning effect of the "low threshold" is also vital because it indicates a complacency about epidemic prevention and control. However, there is obvious heterogeneity in the optimal threshold for detecting early warning signs and their distribution in different cities. Multi-source and multi-point early warning systems should be established via combining internet-based big data in the future to conduct effective and early real-time warning. This would create precious time for the early control of COVID-19 outbreaks. This article is protected by copyright. All rights reserved.

Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer’s disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and non-carriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus (SLE) and familial hypercholesterolemia (FH). Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.

Background The continuous mutation of severe acute respiratory syndrome coronavirus 2 has made the coronavirus disease 2019 (COVID-19) pandemic complicated to predict and posed a severe challenge to the Beijing 2022 Winter Olympics and Winter Paralympics held in February and March 2022. Methods During the preparations for the Beijing 2022 Winter Olympics, we established a dynamic model with pulse detection and isolation effect to evaluate the effect of epidemic prevention and control measures such as entry policies, contact reduction, nucleic acid testing, tracking, isolation, and health monitoring in a closed-loop management environment, by simulating the transmission dynamics in assumed scenarios. We also compared the importance of each parameter in the combination of intervention measures through sensitivity analysis. Results At the assumed baseline levels, the peak of the epidemic reached on the 57th day. During the simulation period (100 days), 13,382 people infected COVID-19. The mean and peak values of hospitalized cases were 2650 and 6746, respectively. The simulation and sensitivity analysis showed that: (1) the most important measures to stop COVID-19 transmission during the event were daily nucleic acid testing, reducing contact among people, and daily health monitoring, with cumulative infections at 0.04%, 0.14%, and 14.92% of baseline levels, respectively (2) strictly implementing the entry policy and reducing the number of cases entering the closed-loop system could delay the peak of the epidemic by 9 days and provide time for medical resources to be mobilized; (3) the risk of environmental transmission was low. Conclusions Comprehensive measures under certain scenarios such as reducing contact, nucleic acid testing, health monitoring, and timely tracking and isolation could effectively prevent virus transmission. Our research results provided an important reference for formulating prevention and control measures during the Winter Olympics, and no epidemic spread in the closed-loop during the games indirectly proved the rationality of our research results. Graphical Abstract

Interference of microtubule dynamics with tubulin-targeted drugs is a validated approach for cancer chemotherapy. Moroidin (

A novel sandwich electrochemical impedimetric immunosensor was proposed to detect apolipoprotein-A1 (Apo-A1), a common biomarker for bladder cancer. The molybdenum disulfide/graphene quantum dot (MoS

Programmable RNA editing tools enable the reversible correction of mutant transcripts, reducing the potential risk associated with permanent genetic changes associated with the use of DNA editing tools. However, the potential of these RNA tools to treat disease remains unknown. Here, we evaluated RNA correction therapy with Cas13-based RNA base editors in the myosin VI p.C442Y heterozygous mutation ( Myo6 C442Y/+ ) mouse model that recapitulated the phenotypes of human dominant-inherited deafness. We first screened several variants of Cas13-based RNA base editors and guide RNAs (gRNAs) targeting Myo6 C442Y in cultured cells and found that mini dCas13X.1-based adenosine base editor (mxABE), composed of truncated Cas13X.1 and the RNA editing enzyme adenosine deaminase acting on RNA 2 deaminase domain variant (ADAR2dd E488Q ), exhibited both high efficiency of A > G conversion and low frequency of off-target edits. Single adeno-associated virus (AAV)–mediated delivery of mxABE in the cochlea corrected the mutated Myo6 C442Y to Myo6 WT allele in homozygous Myo6 C442Y/C442Y mice and resulted in increased Myo6 WT allele in the injected cochlea of Myo6 C442Y/+ mice. The treatment rescued auditory function, including auditory brainstem response and distortion product otoacoustic emission up to 3 months after AAV-mxABE- Myo6 injection in Myo6 C442Y/+ mice. We also observed increased survival rate of hair cells and decreased degeneration of hair bundle morphology in the treated compared to untreated control ears. These findings provide a proof-of-concept study for RNA editing tools as a therapeutic treatment for various semidominant forms of hearing loss and other diseases.

Phytoremediation is an effective approach to remove the challenging pollutant of hexavalent chromium [Cr(VI)] in the environment, however, which requires a relatively long work duration. Herein, we reported the utilization of mung bean (Vigna radiata) as a highly efficient accumulator for Cr(VI). Typically, within a short work duration of only 7 days, 5041 mg · kg−1 of chromium (Cr) could be accumulated in the whole plants of mung bean. Moreover, about 80% of Cr in the mung bean plants are transformed to fractions with low bioavailability. This study demonstrated that mung bean could be a promising candidate for phytoremediation of Cr(VI), not only accumulating but also stabilizing Cr(VI) within very short time.

Cheap transition metal Ni-catalyzed asymmetric hydrogenation of 2-oxazolones was successfully developed, which provided an efficient synthetic strategy to prepare various chiral 2-oxazolidinones wi...

The roles of long noncoding RNA (lncRNA) MACC1-AS1 have been revealed in various tumors. This work aims to explore the roles of lncRNA MACC1-AS1 in the stemness of nonsmall cell lung cancer (NSCLC) cells and the underlying mechanism. We showed that overexpression of MACC1-AS1 enhanced the stemness of NSCLC cells, which is evident as the increased expression of cancer stem cell transcription factors, ALDH1 activity, and sphere-formation capacity, while knockdown of MACC1-AS1 decreased it. RNA-sequencing analysis revealed that the Hippo pathway was mostly enriched in NSCLC cell with MACC1-AS1 overexpression. Further mRNA and western blot analysis showed that ectopic expression of MACC1-AS1 regulated the expression LATS1/2, the critical regulator of Hippo pathway. Additionally, it was found that MACC1-AS1 interacted with up-frameshift 1 (UPF1) to modulate mRNA decay of LATS1/2. Overexpression of LAST1/2 attenuated the promoting effects of MACC1-AS1 overexpression on the stemness of NSCLC cells. Therefore, our results demonstrate the effects of the novel MACC1-AS1/UPF1/LATS1/2 axis in NSCLC cell stemness.

CRISPR-Cas13 systems have recently been employed for targeted RNA degradation in various organisms. However, collateral degradation of bystander RNAs has imposed a major barrier for their in vivo applications. We designed a dual-fluorescent reporter system for detecting collateral effects and screening Cas13 variants in mammalian cells. Among over 200 engineered variants, several Cas13 variants (including Cas13d and Cas13X) exhibit efficient on-target activity but markedly reduced collateral activity. Furthermore, transcriptome-wide off-targets and cell growth arrest induced by Cas13 are absent for these variants. Importantly, high-fidelity Cas13 variants show comparable RNA knockdown activity with wild-type Cas13 but no detectable collateral damage in transgenic mice and adeno-associated virus-mediated somatic cell targeting. Thus, high-fidelity Cas13 variants with minimal collateral effect are now available for targeted degradation of RNAs in basic research and therapeutic applications.

CRISPR-Cas13 systems have recently been used for targeted RNA degradation in various organisms. However, collateral degradation of bystander RNAs has limited their in vivo applications. Here, we design a dual-fluorescence reporter system for detecting collateral effects and screening Cas13 variants in mammalian cells. Among over 200 engineered variants, several Cas13 variants including Cas13d and Cas13X exhibit efficient on-target activity but markedly reduced collateral activity. Furthermore, transcriptome-wide off-targets and cell growth arrest induced by Cas13 are absent for these variants. High-fidelity Cas13 variants show similar RNA knockdown activity to wild-type Cas13 but no detectable collateral damage in transgenic mice or adeno-associated-virus-mediated somatic cell targeting. Thus, high-fidelity Cas13 variants with minimal collateral effects are now available for targeted degradation of RNAs in basic research and therapeutic applications.

Scope Anthocyanin cyanidin-3-O-glucoside (Cy3G) has a great potential in prevention of diabetes and its vascular complications while the underlying mechanisms are still far from clear. Accumulating evidence suggests that endothelial insulin transport plays a critical role in regulating metabolic insulin sensitivity. Whether Cy3G could modulate metabolic insulin resistance via regulating endothelial insulin transport has not been reported yet. Methods and results Palmitic acid (PA)-treated mouse aortic endothelial cells (MAECs) model and high-fat diet (HFD) fed mice model were used. Compared with HFD mice, Cy3G supplementation decrease exogenous insulin content in skeletal muscle and ameliorate metabolic insulin resistance. In culture, Cy3G could directly ameliorate PA-induced impairment on FITC-insulin uptake in MAECs. Mechanistically, Cy3G could effectively decrease inflammatory cytokines and toll-like receptor 4 (TLR4)/ nuclear factor-kappa-B inhibitor alpha (IκBα) activation, and restore the attenuated Akt/eNOS signaling pathway. Blunted nitric oxide synthase with N-nitro-L-arginine methyl ester (L-NAME) could effectively abolish the protective role of Cy3G on endothelial insulin transport and insulin-stimulated glucose utilization in HFD-fed mice. Conclusions These findings suggest that Cy3G supplementation could directly restore the attenuated nitic oxide-mediated endothelial insulin transport and thereby ameliorate metabolic insulin resistance. Our finding might provide a novel explanation for the anti-diabetic effects of Cy3G. This article is protected by copyright. All rights reserved.

As a general method to yield constructions for quasi-cyclic (QC) low-density parity-check (LDPC) codes with girth eight, the greatest-common-divisor (GCD) framework heavily relies on verifying a type of inequalities, referred to as GCD constraints. An algorithm is developed in this letter to automatically verify GCD constraints without conducting any manual analysis, by bounding from above the GCD of a fixed integer and an integer in the form of linear function. As an application of the algorithm, a set of novel constructions based on GCD framework is proposed. From these new constructions, four novel bounds on the size of circulant permutation matrices (CPMs) are formulated, such that girth-eight QC-LDPC codes always exist for any CPM size greater than or equal to the bounds. The new bound for column weight of 6 slightly improves the existing best one, and those for column weights from 7 to 9 significantly strengthen the state-of-the-art ones by decreasing from essentially a cubic or biquadratic power of row weight to a quadratic power of row weight.

Summary Chiral cyclic sulfamidates are useful building blocks to construct compounds, such as chiral amines, with important applications. Often these compounds can only be generated through expensive precious metal catalysts. Here, Ni(OAc)2/(S, S)-Ph-BPE-catalyzed highly efficient asymmetric hydrogenation of cyclic sulfamidate imines was successfully developed, affording various chiral cyclic sulfamidates with high yields and excellent enantioselectivities (up to 99% yield, >99% enantiomeric excess [ee]). This Ni-catalyzed asymmetric hydrogenation on a gram scale has been achieved with only 0.1 mol% catalyst loading in 99% yield with 93% ee. Other types of N-sulfonyl ketimines were also hydrogenated well to obtain the corresponding products with >99% conversion, 96%–97% yields, and 97%–>99% ee. In addition, this asymmetric methodology could produce other enantioenriched organic molecules, such as chiral β-fluoroamine, amino ether, and phenylglycinol. Moreover, a reasonable catalytic cycle was provided according to the deuterium-labeling studies, which could reveal a possible mechanism for this Ni-catalyzed asymmetric hydrogenation., Graphical Abstract, Highlights • Ni-catalyzed asymmetric hydrogenation of cyclic sulfamidate imines • Efficient preparation of enantioenriched cyclic sulfamidates • Broad range of substrate scope • Gram-scale asymmetric hydrogenation with high TON, Chemistry; Catalysis; Organic Chemistry; Stereochemistry

So far, all existing quantum oblivious transfer protocols focused on realization of the oblivious transfer of a classical bit or classical bit-string. In this paper, p-Rabin quantum oblivious transfer of a qubit protocol is achieved by using a probabilistic teleportation protocol. As the probabilistic teleportation protocol is able to transfer an (un)known pure state with a certain probability, this feature makes the probabilistic teleportation protocol well fit for Rabin oblivious transfer. Here, this is the first time that the concept of qubit oblivious transfer is presented. Furthermore, p-Rabin quantum oblivious transfer of a qubit protocol can also be used for oblivious of a bit by encoding classical bit with two pre-agreed orthogonal states. Finally, security analysis shows that the protocol satisfies the security requirements of oblivious transfer, and what’s more, the discussion of relationship with no-go theorem demonstrates that the probabilistic teleportation protocol is able to evade the no-go theorem.

This letter presents two novel adaptive bit-local threshold bit-flipping algorithms for improving the hard-decision decoding performance of LDPC codes. The threshold of each bit can be changed adaptively to maximize the number of corrected errors during the iterations. The proposed methods require only logical operations during decoding and can be realized easily by hardware. Compared with the existing adaptive threshold BF algorithm, the proposed algorithms achieve better performance while removing the need for the delay-inducing global maximum operations, thus facilitating high-throughput decoding.

Non-muscle myosin IIA (NMIIA) protein plays an important role in cell cytokinesis and cell migration. The role and underlying regulatory mechanisms of NMIIA in pancreatic cancer (PC) remain elusive. We found that NMIIA is highly expressed in PC tissues and contributes to PC poor progression by using open microarray datasets from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and PC tissue arrays. NMIIA regulates β-catenin mediated EMT to promote the proliferation, migration, invasion, and sphere formation of PC cells in vitro and in vivo. NMIIA controls the β-catenin transcriptional activity by interacting with β-catenin. Moreover, MEK/ERK signaling is critical in MLC2 (Ser19) phosphorylation, which can mediate NMIIA activity and regulate Wnt/β-catenin signaling. These findings highlight the significance of NMIIA in tumor regression and implicate NMIIA as a promising candidate for PC treatment.

Rh-catalyzed asymmetric hydrogenation of prochiral substituted benzo[b]thiophene 1,1-dioxides was successfully developed, affording various chiral 2,3-dihydrobenzo[b]thiophene 1,1-dioxides with high yields and excellent enantioselectivities (up to 99% yield and >99% ee). In particular, for challenging substrates, such as aryl substituted substrates with sterically hindered groups and alkyl substituted substrates, the reaction proceeded smoothly in our catalytic system with excellent results. The gram-scale asymmetric hydrogenation proceeded well with 99% yield and 99% ee in the presence of 0.02 mol% (S/C = 5000) catalyst loading. The possible hydrogen-bonding interaction between the substrate and the ligand may play an important role in achieving high reactivity and excellent enantioselectivity.

Objective To investigate the prognostic factors of patients with pancreatic neuroendocrine tumor (pNETs) after surgical resection, and to analyze the value of enucleation for pNETs without distant metastasis that are well-differentiated (G1) and have a diameter ≤ 4 cm. Methods Data from pNET patients undergoing surgical resection between 2004 and 2017 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan–Meier analysis and log-rank testing were used for the survival comparisons. Adjusted HRs with 95% CIs were calculated using univariate and multivariate Cox regression models to estimate the prognostic factors. P Results This study found that female, cases diagnosed after 2010, and pancreatic body/tail tumors were protective factors for good survival, while histological grade G3, a larger tumor size, distant metastasis, AJCC 8th stage III-IV and age over 60 were independent prognostic factors for a worse OS/CSS. For the pNETs that were well-differentiated (G1) and had a tumor diameter ≤ 4 cm, the type of surgery was an independent factor for the long-term prognosis of this group. Compared with pancreaticoduodenectomy and total pancreatectomy, patients who were accepted enucleation had better OS/CSS. Conclusion For pNETs patients undergoing surgical resection, sex, year of diagnosis, tumor location, pathological grade, tumor size, distant metastasis, race, and age were independent prognostic factors associated with the OS/CSS of patients. For pNETs patients with G1 and a tumor diameter less than 4 cm, if the tumor was located over 3 mm from the pancreatic duct, enucleation may be a wise choice.

The study aimed to explore the regulatory mechanism of micro ribonucleic acid (miR)-130a in the autophagy of bladder cancer cells through cylindromatosis (CYLD).Human bladder cancer T24 cell line was used as the objects of the study. After miR-130a was knocked down using small-interfering RNA (siRNA) in T24 cell line, the changes in expressions of miR-130a and CYLD in each group were detected via quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The cell proliferation in each group was detected using cell counting kit-8 (CCK8) assay and flow cytometry. The changes in mRNA and protein levels of microtubule-associated protein 1 light chain 3 (LC3) and Beclin1 were determined using qRT-PCR and Western blotting. The autolysosomes were detected through acridine orange (AO)/ethidium staining bromide (ER) staining. Moreover, CYLD was knocked down using siRNA, and then the changes in mRNA expressions of miR-130a, LC3 and Beclin1 in each group were detected through qRT-PCR.After interference in miR-130a with siRNA, miR-130a-siRNA group had a significantly lower mRNA expression of miR-130a compared with NC-siRNA group and a significantly higher mRNA expression of CYLD (p0.05), obviously inhibited cell proliferation (p0.05), and decreased significantly mRNA and protein expressions of LC3 showing Beclin1 (p0.05), and an evidently smaller number of autolysosomes. After knockdown of CYLD using siRNA, the mRNA expression of miR-130a had no significant changes (p0.05), while the mRNA expressions of LC3 and Beclin1 declined significantly in CYLD-siRNA group compared with those in NC-siRNA group (p0.05).MiR-130 can promote the autophagy of bladder cancer cells through regulating CYLD, thus facilitating the proliferation of tumor cells.

Hyperthermia is one of the most widely employed adjuvant treatments for cancer, especially for hyperthermic intraperitoneal chemotherapy, and has few side effects. Gastric cancer has various hyperthermia sensitivities, but the exact molecular mechanisms remain to be elucidated. In the present study, western blotting was performed to detect differential expression of proteins that have been reported to be upregulated in gastric cancer. Following knockdown of these proteins, apoptosis was measured by Annexin V‑FITC/propidium iodide (PI) double staining and hyperthermia treatment was applied. To evaluate the effect of cyclin‑dependent kinase 6 (CDK6) on hyperthermia‑induced apoptosis, CDK6 was knocked down or inhibited by the addition of a specific inhibitor and subsequent PI staining and cell proliferation, migration and invasion assays were performed. Hyperthermia‑induced protein kinase B (AKT) expression and phosphorylation inhibition were detected. As demonstrated in the present study, the hyperthermia‑induced proteins kinesin family member 11 (KIF11), cyclin‑dependent kinase 6 (CDK6), stromal antigen 2, NIMA‑related kinase 2 and karyopherin subunit α 4 were highly expressed in gastric cancer cells, including SH‑10‑TC and HGC‑27 cells. Knockdown of KIF11 significantly increased apoptosis without hyperthermia treatment and CDK6 significantly increased hyperthermia‑induced apoptosis, prompting the present study to focus on CDK6. It was further confirmed that CDK6 activity was critical for decreasing hyperthermia‑induced apoptosis and for cell proliferation. Hyperthermia‑induced AKT expression and phosphorylation inhibition is potentially the main cause of CDK6 transcriptional upregulation. Taken together, these findings demonstrated that CDK6 is upregulated via hyperthermia‑induced AKT inhibition and subsequently protected gastric cancer cells from hyperthermia‑induced apoptosis, indicating that it is a potential therapeutic target to sensitize gastric cancer cells to hyperthermia‑based therapy.

The roles of long noncoding RNA (lncRNA) MACC1-AS1 have been revealed in various tumors. This work aims to explore the roles of lncRNA MACC1-AS1 in the stemness of nonsmall cell lung cancer (NSCLC) cells and the underlying mechanism. We showed that overexpression of MACC1-AS1 enhanced the stemness of NSCLC cells, which is evident as the increased expression of cancer stem cell transcription factors, ALDH1 activity, and sphere-formation capacity, while knockdown of MACC1-AS1 decreased it. RNA-sequencing analysis revealed that the Hippo pathway was mostly enriched in NSCLC cell with MACC1-AS1 overexpression. Further mRNA and western blot analysis showed that ectopic expression of MACC1-AS1 regulated the expression LATS1/2, the critical regulator of Hippo pathway. Additionally, it was found that MACC1-AS1 interacted with up-frameshift 1 (UPF1) to modulate mRNA decay of LATS1/2. Overexpression of LAST1/2 attenuated the promoting effects of MACC1-AS1 overexpression on the stemness of NSCLC cells. Therefore, our results demonstrate the effects of the novel MACC1-AS1/UPF1/LATS1/2 axis in NSCLC cell stemness.

GNSS-R microwave remote sensing technology has increasingly become an important branch of satellite navigation applications. In June 2019, China successfully achieved the deployment of BuFeng-1 A/B satellites by Chinese first time sea platform launch. BuFeng-1 is mainly to conduct GNSS-R on-orbit tests of sea wind field detection and its applications. In the processing method, the power self-calibration method is introduced to eliminate the influence of the GNSS-R load receiving link changes by the space environment. Then, the GNSS-R observation geometric change by the GNSS-R geometry is corrected. Finally, DDMs with power self-calibration and geometric correction can directly show an agreement with the sea surface wind speeds. On-orbit results show that the detection accuracy is of 2.63 m/s up at 30 m/s of wind speeds by European Centre for Medium-Range Weather Forecasts (ECMWF) and 1.97 m/s at 20 m/s compared with ASCAT observations, which are accorded to the pre-design requirements of 2 m/s or 10%.

Figure S1. Comparison of different protocols for ASC differentiation in vitro. Human B cells were sorted by CD19 beads from PBMC of healthy donors and stimulated with ten different conditions for 5 days. Frequencies of CD19+CD20-CD27hiCD38hi ASC (A) and immunoglobulins from culture supernatant (B) were shown. (C) FCM plots and (D) cumulative data of ASC generation following CpG/IL-2/IL-10 stimulation at different time points were shown (n = 3). One representative of at least three independent experiments was shown. Data were shown as mean ± SEM and analyzed by one-way ANOVA with Bonferroni correction for multiple comparisons (C). *P

Long non-coding RNAs (lncRNAs) show great potential as therapeutic targets in many diseases including hepatocellular carcinoma (HCC). Here, we aimed to investigate the clinical significance and function of lncRNA CDKN2B antisense RNA 1 (CDKN2B-AS1) in HCC. Here, we identified a novel oncogenic lncRNA CDKN2B-AS1, which was highly expressed in HCC and positively associated with large tumor size, microvascular invasion, high tumor grade, advanced tumor stage and reduced survival of HCC patients. CDKN2B-AS1 knockdown inhibited cell proliferation, migration and invasion, and induced G1 arrest and apoptosis of HCC cells in vitro, and CDKN2B-AS1 silencing suppressed tumor growth and metastasis of HCC in vivo. In accordance, CDKN2B-AS1 overexpression accelerated HCC cell growth and metastasis. Mechanistically, CDKN2B-AS1 promoted nucleosome assembly protein 1 like 1 (NAP1L1) expression by sponging let-7c-5p, thereby activated PI3K/AKT/mTOR signaling in HCC cells. Notably, NAP1L1 restoration abolished the effects of CDKN2B-AS1 silencing on HCC cell growth and metastasis. CDKN2B-AS1, an oncogenic lncRNA of HCC, promoted NAP1L1-mediated PI3K/AKT/mTOR signaling by acting as a molecular sponge of let-7c-5p. Our findings indicate that CDKN2B-AS1 may be a potential prognostic biomarker and a candidate target for HCC therapy.

Regular exercise is confirmed as a lifestyle treatment option for all obstructive sleep apnea (OSA) patients. It has beneficial effects other than weight loss, although the mechanisms remain unclear. Autonomic function imbalance plays an important role in OSA, so that it is meaningful to observe the effect of exercise on autonomic function. Seventy mild to moderate OSA patients were divided into two groups. The exercise group received a 12-week exercise program prescribed according to their first cardiopulmonary exercise tests, while the control group kept previous lifestyle. All patients underwent blood tests, cardiopulmonary exercise tests, and polysomnography studies at enrollment and at the 12-week’s follow-up. At the end of 12 weeks, three patients of the exercise group did not complete the program due to lack of adherence. The current study showed 12-week aerobic exercises could improve body mass index (27.6 ± 4.7 kg/m2 vs. 24.5 ± 4.2 kg/m2, P