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Aims: This work was designed to identify the subgroup of advanced hepatocellular carcinoma (HCC) patients for whom treatments containing immune checkpoint blockers (ICBs) were most effective. Materials & methods: A meta-analysis was performed to explore the subgroup population with the greatest benefit of treatments containing ICBs. Results: A total of 2228 patients from four randomized control trials were included. Treatments containing ICBs had better overall survival, progression-free survival and higher objective response rate over treatment without ICBs. Subgroup analysis revealed that treatments containing ICBs were highly effective in improving the overall survival of males, patients with macrovascular invasion and/or extrahepatic spread and viral-related HCC patients. Conclusion: Treatments containing ICBs are more effective for males, patients with macrovascular invasion and/or extrahepatic spread and viral-related HCC patients.

The prognostic value of alpha-fetoprotein (AFP) response for efficacy of targeted therapy or immune checkpoint inhibitors (ICIs) has not been established. The purpose of this meta-analysis is to elucidate the relationship between AFP response and survival outcomes in hepatocellular carcinoma (HCC) patients who received targeted therapy or ICIs. The hazard ratio (HR) with 95% confidence interval (CI) was used to evaluate the relationship between AFP response and overall survival (OS)/progression-free survival (PFS). Twenty-six articles containing 3056 HCC patients were finally included in the study. The pooled results showed that after targeted therapy or ICIs, patients with decrease in AFP had better prognosis (OS:HR = 0.48, 95%CI:0.40–0.56; PFS:HR = 0.39, 95%CI:0.33–0.46), while patients with increase in AFP had worse prognosis (OS:HR = 2.30, 95%CI:1.82–2.89; PFS:HR = 2.34, 95%CI = 1.69–3.24). Subgroup analysis revealed that compared to AFP decrease >50%, AFP decrease >20% can better predict the prognosis of patients who received targeted therapy (OS:HR = 0.51, 95%CI:0.41–0.62; PFS:HR = 0.39, 95%CI:0.30–0.51) or ICIs treatment (OS:HR = 0.34, 95%CI:0.16–0.71; PFS:HR = 0.22, 95%CI:0.10–0.47), and 8 weeks after targeted therapy may be the appropriate time point for AFP assessment. AFP decrease >20% within 8 weeks may be the appropriate definition for early AFP response which probably works best in predicting the efficacy of therapy. The review was not registered.

Objective: This meta-analysis was designed to explore the association between the systemic immune–inflammation index (SII) and the therapeutic effect of immune checkpoint inhibitors. Materials & methods: The authors retrieved relevant studies published before May 25, 2022. Hazard ratio (HR) with 95% CI was used to evaluate the relationship between SII and overall survival (OS) and progression-free survival (PFS). Results: 14 articles comprising 2721 patients were included in this study. The pooled results proved that high SII levels were closely related to poor prognosis in cancer patients receiving immune checkpoint inhibitors (OS HR = 2.40; 95% CI: 2.04–2.82; PFS HR = 1.57; 95% CI: 1.33–1.86) and that an SII value of 750 was appropriate as a cut-off value (OS HR = 2.20; 95% CI: 1.83–2.63; PFS HR = 1.54; 95% CI: 1.33–1.80). Conclusion: High SII levels (>750) may be an indicator of worse OS and PFS in cancer patients treated with immune checkpoint inhibitors.

Gastric cancer (GC) progression is related with gene regulations.This study explored underlying regulatory axis of circRNA PVT1 (circPVT1) in GC.GC cell lines were detected for circPVT1 expression with the normal mucous epithelial cell GES-1 as control. After regulation of circPVT1, miR-423-5p and SMAD3 expression through transfection, CCK8 evaluated the cell viability, Transwell measured the migratory and invasive capability of cells. Luciferase verified the paired bindings between miR-423-5p and CircPVT1 or SMAD3. The functions of CircPVT1/miR-423-5p/SMAD3 were evaluated using RT-PCR, CCK8, Transwell assays. Western blot analyzed EMT-related proteins and phosphorylation of Smad3 in GC cells. Immunofluorescence method was used to evaluate the EMT-related proteins as well.CircPVT1 displayed higher expression in GC cells and knockdown led to decrease in cell growth, invasion and migration. CircPVT1 was targeted by miR-423-5p as a ceRNA of SMAD3. miR-423-5p upregulation suppressed both cicRNA PVT1 and SMAD3 in GC cells. Decrease in SMAD3 expression suppressed CircPVT1 by releasing miR-423-5p in cells, inhibiting cell growth, invasion and migration and suppressing the EMT process.CircPVT1 modulated cell growth, invasion and migration through EMT mediation in gastric cancer through miR-423-5p/Smad3 pathway.

Immune checkpoint inhibitors (ICIs) have been explored as first-line treatment in various types of previously untreatable malignancies, while limited evidence is available on the management of hepatitis B virus (HBV) in patients undergoing immunotherapy. We systematically reviewed data concerning challenges of hepatic adverse events including HBV reactivation and hepatitis in patients with chronic HBV infection undergoing immunotherapy.A systematic search was conducted in Medline, web of science, Embase and Cochrane library up to May 31, 2022. Studies reporting the safety profile of ICIs in patients with HBV infection were eligible. Meta-analyses were conducted to generate odds ratios (ORs) with 95% confidence intervals (CIs).A total of 13 studies including 2561 patients were included for meta-analysis. The overall incidence rates of HBV reactivation in patients with chronic HBV infection and past HBV infection were 1.0% (95% CI 0-3%) and 0% (95% CI 0-0%), respectively. Among patients with chronic HBV infection, the incidence rates of HBV reactivation were 1.0% (95% CI 0-2%) and 10.0% (95% CI 4-18%) for patients with and without antiviral prophylaxis, respectively. Patients with chronic HBV infection were at a higher risk of HBV reactivation compared with those with past HBV infection [OR = 8.69, 95% CI (2.16-34.99)]. Antiviral prophylaxis significantly reduced the risk of HBV reactivation [OR = 0.12, 95% CI (0.02-0.67)] and HBV-associated hepatitis [OR = 0.05, 95% CI (0.01-0.28)] in patients with chronic HBV infection.Prophylactic antiviral therapy should be administered to patients with chronic HBV infection undergoing anticancer immunotherapy. Patients with past HBV infection are at lower risk of HBV reactivation compared with those with chronic HBV infection, they could be initiated with antiviral prophylaxis or monitored with the intent of on-demand antiviral therapy.

Background: Intracellular copper homeostasis requires a complex system. It has shown considerable prospects for intervening in the tumor microenvironment (TME) by regulating copper homeostasis and provoking cuproptosis. Their relationship with hepatocellular carcinoma (HCC) remains elusive.Methods: In TCGA and ICGC datasets, LASSO and multivariate Cox regression were applied to obtain the signature on the basis of genes associated with copper homeostasis and cuproptosis. Bioinformatic tools were utilized to reveal if the signature was correlated with HCC characteristics. Single-cell RNA sequencing data analysis identified differences in tumor and T cells’ pathway activity and intercellular communication of immune-related cells. Real-time qPCR analysis was conducted to measure the genes’ expression in HCC and adjacent normal tissue from 21 patients. CCK8 assay, scratch assay, transwell, and colony formation were conducted to reveal the effect of genes on in vitro cell proliferation, invasion, migration, and colony formation.Results: We constructed a five-gene scoring system in relation to copper homeostasis and cuproptosis. The high-risk score indicated poor clinical prognosis, enhanced tumor malignancy, and immune-suppressive tumor microenvironment. The T cell activity was markedly reduced in high-risk single-cell samples. The high-risk HCC patients had a better expectation of ICB response and reactivity to anti-PD-1 therapy. A total of 156 drugs were identified as potential signature-related drugs for HCC treatment, and most were sensitive to high-risk patients. Novel ligand-receptor pairs such as FASLG, CCL, CD40, IL2, and IFN-Ⅱ signaling pathways were revealed as cellular communication bridges, which may cause differences in TME and immune function. All crucial genes were differentially expressed between HCC and paired adjacent normal tissue. Model-constructed genes affected the phosphorylation of mTOR and AKT in both Huh7 and Hep3B cells. Knockdown of ZCRB1 impaired the proliferation, invasion, migration, and colony formation in HCC cell lines.Conclusion: We obtained a prognostic scoring system to forecast the TME changes and assist in choosing therapy strategies for HCC patients. In this study, we combined copper homeostasis and cuproptosis to show the overall potential risk of copper-related biological processes in HCC for the first time.

Background: Combination immunotherapy have gradually become the mainstay of systematic therapy for hepatocellular carcinoma (HCC), however, prescribing immunotherapies perioperatively has the potential to reduce tumor activity, while increasing the resection rate and improving prognoses. This study investigated the efficacy and safety of preoperative combined immunotherapies for patients with initially unresectable HCC. Methods:This retrospective, real-world study involved patients with initially unresectable HCC receiving combined immunotherapies based on PD-1/L1 blockade before surgery. Tumor treatment responses, pathological manifestations in postoperative specimens and overall survival (OS) were evaluated. Treatment related adverse events (AEs) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE, version 4.0). Results: The study consecutively included 54 initially unresectable HCC patients and 34 patients were evaluated the safety, efficacy and possibility of subsequent radical surgery. Among these patients with surgical resection, 57.1% (n=8) receiving combination immunotherapy before surgery achieved a partial response (PR), which highlighted a 30% reduction in tumor size. Pathological evaluation of postoperative specimens confirmed that 21.4% (n=3) achieved complete responses. 78.6% (n=11) achieved partial responses. 28.6% (n=4) encountered grade 3 or 4 AEs out of 14 patients. The main AEs included fatigue (n=11; 78.6%), leukocytopenia (n=8; 57.1%,) and aspartate aminotransferase (AST) elevation (n=6; 42.9%). Conclusions: After the application of combination immunotherapy, patients should be comprehensively evaluated whether they meet the criteria for surgical resection. This surgical resection following by combination immunotherapy might effectively control tumor progression and could improve the prognosis at least for some patients with initially unresectable HCC.

A series of extensional structures, including the southern Tibet detachment system (STDS), the north-south trending rifts (NSTR), and the northern Himalayan gneiss dome (NHGD), developed from the collision and compression between the Indian and Eurasian plates. These tectonic movements were accompanied by magmatism and polymetallic mineralization. Cuona Rift (CR) is located on the STDS next to the Yalaxiangbo Dome (YD) and passes through the Zhegucuo-longzi fault (ZLF), the Lhozhag fault (LZF), the Rongbu-Gudui fault (RGF), the Cuonadong dome (CD), and the YD. The study area contains numerous metal deposits, such as rare metal ore, lead zinc ore, gold deposits, and two geothermal fields, i.e., the Cuona geothermal field (CGF) and the Gudui geothermal field (GGF). Current research on the geological structures from the STDS to the YD is mainly based on magnetotelluric and natural seismic imaging. These surveys have a low resolution, making it impossible to image the shallow crust in detail. This study obtained about a 112 km S-wave velocity profile from the STDS to the YD using the multichannel surface wave imaging method. The profile results indicated that the average thickness of the sedimentary layer from the STDS to the YD is 400–500 m, while it is more than 800 m at certain fault zones. The CD is connected to the high-velocity body below the Zhaxikang ore concentration area (ZOCA) and may have the same provenance. The thermal conductivity reveals that the CGF, the GGF, and the ZOCA have high values and a more intense thermal radiation capacity. This drives the migration and circulation of the thermal fluids in the CGF and the GGF, causing them to continuously transmit heat to the shallow surface along the fault system. The migration of the thermal fluids extracts useful elements from the geological bodies through which it flows. When these elements mix with the atmospheric infiltration water, it precipitates to form the Zhaxikang hydrothermal superimposed transformation type lead-zinc polymetallic deposit.

Preliminary studies have suggested that soluble programmed death-1 (sPD-1) and soluble programmed cell death ligand-1 (sPD-L1) have prognostic implications in many malignant tumors. However, the correlation between sPD-1/sPD-L1 level and prognosis of hepatocellular carcinoma (HCC) is still unclear. We searched several electronic databases from database inception to October 7, 2021. Meta-analyses were performed separately for overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS), time to progression (TTP), and tumor-free survival (TFS). Random effects were introduced to this meta-analysis. The correlation between sPD-1/sPD-L1 level and prognosis was evaluated using hazard ratios (HRs) with 95% confidence intervals (95%CIs). A total of 11 studies (1291 patients) were incorporated into this meta-analysis, including seven on sPD-L1, two on sPD-1, and two about both factors. The pooled results showed that high sPD-L1 level was associated with worse OS (HR = 2.46, 95%CI 1.74–3.49, P

The introduction of immune checkpoint inhibitors (ICIs) has reshaped the therapy of hepatocellular carcinoma (HCC). ICIs are a novel therapy with frequent adverse events (AEs), including treatment-related adverse events (trAEs) and immune-related adverse events (irAEs). However, no comprehensive overview of the toxicity spectrum of ICIs in HCC patients has been provided. Electronic databases were searched to identify eligible studies. A meta-analysis of the incidence rate of AEs in HCC patients treated with ICIs was performed. Lastly, the prognostic value of irAEs in HCC patients treated with ICIs was verified. Forty-seven studies with 6472 participations met the inclusion criteria. The pooled all-grade trAEs incidence rate was 83.4% (95% confidence interval [95% CI] 77.0-89.1%), ≥ grade 3 trAEs incidence rate was 33.0% (95% CI 26.9-39.5%), all-grade irAEs incidence rate was 34% (95% CI 22-47%), and ≥ grade 3 irAEs incidence rate was 9% (95% CI 5-14%). Aspartate aminotransferase (AST) increase (38%, 95% CI 35-40%) is the most common trAEs. Fatigue (14%, 95% CI 7-23%) is the most common irAEs. The pooled results also showed that 18.8% (95% CI 13.2-25.2%) of patients required systemic steroid therapy due to AEs, while 6.6% (95% CI 4.6-9.0%) of patients withdrew from treatment due to AEs. Additionally, patients experiencing irAEs may have a better progression-free survival (PFS) (multivariate analysis: hazard ratio [HR] = 0.41, 95% CI 0.27-0.61, I

Trace elements, such as iodine and selenium (Se), are vital to human health and play an essential role in metabolism. They are also important to thyroid metabolism and function, and correlate with thyroid autoimmunity and tumors. Other minerals such as iron (Ir), lithium (Li), copper (Co), zinc (Zn), manganese (Mn), magnesium (Mg), cadmium (Cd), and molybdenum (Mo), may related to thyroid function and disease. Normal thyroid function depends on a variety of trace elements for thyroid hormone synthesis and metabolism. These trace elements interact with each other and are in a dynamic balance. However, this balance may be disturbed by the excess or deficiency of one or more elements, leading to abnormal thyroid function and the promotion of autoimmune thyroid diseases and thyroid tumors.The relationship between trace elements and thyroid disorders is still unclear, and further research is needed to clarify this issue and improve our understanding of how trace elements mediate thyroid function and metabolism. This paper systematically reviewed recently published literature on the relationship between various trace elements and thyroid function to provide a preliminary theoretical basis for future research.

Cultivating the dedicated biomass crop Miscanthus on marginal land is a sustainable means of avoiding competition with food crops for arable land. A large proportion of global marginal land is saline–alkaline; however, little is known about the performance of Miscanthus in saline-alkaline soil. In this study, Miscanthus × giganteus and ten other Miscanthus hybrids grown in the Yellow River Delta were exposed to low and saline–alkaline soils during the 2016–2018 growing season to evaluate the agronomic traits, biomass quality and the potential productive index of eleven Miscanthus genotypes. Plant biomass, plant height, and tiller number significantly decreased in high saline–alkaline soil. In particular, the average plant biomass of ten Miscanthus hybrids in low saline–alkaline soil in 2017 and 2018 were 0.21 and 2.25 kg per plant, respectively, and in high saline-alkaline soil were 0.13 and 0.65 kg per plant, respectively. Cell wall, cellulose, and nitrogen content of all genotypes significantly decreased in high saline–alkaline soil, while hemicellulose, ash, sodium, potassium, magnesium, and calcium content significantly increased. However, high saline–alkaline soil had no observable impact on lignin content of Miscanthus biomass. The effect of high saline-alkaline on biomass quality parameters could provide important information for the application of Miscanthus biomass in saline-alkaline soil. The selected genotypes (A5) could be considered as breeding materials in saline-alkaline soil.

BackgroundHigh serum triglyceride (STG) level is a well-established pathogenic factor for cardiovascular diseases and is associated with the risk of various malignancies. Nevertheless, the role of STG level in intrahepatic cholangiocarcinoma (ICC) remains uncertain.MethodsA total of 631 ICC patients treated with curative hepatectomy in two centers (517 in the discovery set and 114 in the validation set) were retrospectively analyzed. Kaplan–Meier survival analysis was used to assess the outcomes of the patients with different STG levels. Time-dependent receiver operating characteristic (ROC) analysis was conducted to compare the prognostic value of STG with other established indexes. The Triglyceride-Albumin-Globulin (TAG) grade was introduced and evaluated using the time-dependent area under curves (AUC) analysis and decision curve analysis (DCA).ResultsPatients with increased STG levels and decreased albumin-globulin score (AGS) were correlated with improved overall survival (OS) and recurrence-free survival (RFS). STG level ≥ 1 mmol/L was an independent protective factor for surgically treated ICC patients. The predictive value of the TAG grade was superior to the STG or the AGS alone. In decision curve analysis, the net benefits of the TAG grade in the discovery and validation set were higher than STG and AGS.ConclusionThe current study presented strong evidence that ICC patients with higher preoperative STG levels had preferred long-term surgical outcomes. The novel nutritional score based on serum triglyceride, albumin and globulin levels was inextricably linked to the prognosis of the surgically treated ICC patients. Evaluation of the TAG grade before curative hepatectomy may be beneficial for risk stratification and clinical decision support.

Next-generation gene and engineered-cell therapies benefit from incorporating synthetic gene networks that can precisely regulate the therapeutic output in response to externally administered signal inputs that are safe, readily bioavailable and pleasant to take. To enable such therapeutic control, a mammalian gene switch is designed to be responsive to the natural sweetener xylose and its functionality is assessed in mouse studies. The gene switch consists of the bacterial transcription regulator XylR fused to a mammalian transactivator, which binds to an optimized promoter in the presence of xylose, thereby allowing dose-dependent transgene expression. The sensitivity of SWEET (sweetener-inducible expression of transgene) is improved by coexpressing a xylose transporter. Mice implanted with encapsulated SWEET-engineered cells show increased blood levels of cargo protein when taking xylose-sweetened water or coffee, or highly concentrated apple extract, while they do not respond to intake of a usual amount of carrots, which contain xylose. In a proof-of-concept therapeutic application study, type-1 diabetic mice engineered with insulin-expressing SWEET show lowered glycemia and increased insulin levels when administered this fairly diabetic-compliant sweetener, compared to untreated mice. A SWEET-based therapy appears to have the potential to integrate seamlessly into patients' life-style and food habits in the move toward personalized medicine.

Most patients with hepatocellular carcinoma (HCC) have underlying cirrhosis and a compromised liver function. Immune checkpoint inhibitors (ICIs) have emerged as an important approach for HCC treatment. The purpose of our study was to explore the prognostic significance of liver function in HCC patients receiving ICIs.Hazard ratios (HR) with 95% confidence intervals (CI) were used to evaluate the relationship between liver function and overall survival (OS)/progression-free survival (PFS).41 articles with 4483 patients with HCC were included. The pooled results revealed that either Child-Pugh score (OS:HR = 2.01,95 %CI:1.69-2.38; PFS:HR = 1.39,95 %CI:1.15-1.68) or albumin-bilirubin (ALBI) score (OS:HR = 2.04,95 %CI:1.55-2.69; PFS:HR = 1.42,95 %CI:1.21-1.67) can predict the patient prognosis. The Child-Pugh score has some degree of subjectivity, and the ALBI score can better stratify patients. Therefore, the ALBI score was used to evaluate patients' liver function and determine treatment options. Further subgroup analysis found that the results of prospective studies were statistically significant only for the ALBI score with regards to OS (HR = 1.69,95 %CI:1.26-2.26). Meanwhile, the effect of liver function on the efficacy of ICIs in the large-sample studies was not as obvious as that in small-sample studies. Moreover, the incidence of adverse events did not significantly increase in patients with impaired liver function.Poor liver function is associated with a poor prognosis in patients with HCC receiving ICIs. The ALBI score is simpler and reliable for patient stratification than the Child-Pugh score. Although the survival time of patients with impaired liver function may be relatively short, ICIs still have great potential for therapeutic applications.

Transarterial embolization (TAE) is a personalized technology that offers precise delivery of chemotherapeutic drugs or selective internal radiation therapy for hepatocellular carcinoma (HCC). Beta-emitting radionuclide embolisms for TAE (β-based TARE) are commonly used in the clinic via inducing biochemical lethality on tumor cells, while alpha-emitting radionuclides-based embolisms for TAE (α-based TARE) are still under study. The feeding artery plays a key role in tumor growth, metastasis, and recurrence. In this research, the auricular central arteries (ACAs) of rabbits were embolized with silk fibroin-based microspheres (SFMs) or SFMs integrated with α (Ra-223) or β (I-131) radionuclides to investigate the influence on vessels. TARE-induced tissue necrosis and the following neovascularization were measured by pathological analysis and 68Ga-DOTA-RGD PET/CT. The results showed that, compared to I-131, Ra-223 enhanced the growth inhibition of human hepatoma cells Huh-7 and induced more DNA double-strand breaks in vascular smooth muscle cells. Unlike β-based TARE, which mainly led to extensive necrosis of surrounding tissues, α-based TARE induced irreversible necrosis of a limited area adjacent to the embolized vessels. RGD PET revealed the inhibition on neovascularization in α-based TARE (SUVmax = 0.053 ± 0.004) when compared with normal group (SUVmax = 0.099 ± 0.036), the SFMs-lipiodol group (SUVmax = 0.240 ± 0.040), and β-based TARE (SUVmax = 0.141 ± 0.026), owing to the avoidance of the embolism-induced neovascularization. In conclusion, α-based TARE provided a promising strategy for HCC treatments via destroying the embolized vessels and inhibiting neovascularization.

As interference waves in deep reflection data processing, surface waves are often suppressed as noise, but surface waves carry considerable underground media information, including structural information and the physical properties of rocks. Reasonable extraction and use of surface wave signals are of great significance when studying shallow characteristics. Deep reflection data are collected using large offsets, trail spacing, and explosive sources. The surface wave energy tends to be stronger, and the high-frequency surface wave signal is abundant. After extraction and inversion, the shallow shear wave velocity structure can be obtained. Near the Cuonadong dome in the southern Tibetan detachment system (STDS), a large number of leucogranites are developed in the core, containing important rare metal minerals and high metallogenic potential. However, studies regarding the shallow structure in this region are rare. In this paper, we use deep reflection data from a profile through the Cuonadong dome to obtain the S-wave velocity structure of the study area by extracting the surface wave fundamental-mode dispersion curve and inversion. Combined with regional geological and magnetotelluric data, we supposed that the thickness of the Cuonadong dome sediment layer ( 2.2 km/s), and the horizontal S-wave velocity changes greatly, which is mainly related to the destruction of magmatic activity since the Miocene. These understandings of the structure and velocity field of the Cuonadong dome can provide a powerful geophysical basis for establishing the dome structure model and searching for hidden ore bodies. Graphical abstract

Cage is the core component of a rolling element bearing, and its dynamic characteristics directly determine the performance and service life of a bearing. Metamaterial is a new structural material with topology optimization design, which has many special physical properties that traditional materials do not possess. Utilizing 3D printing technology to prepare metamaterials can increase manufacturing flexibility, give full play to its advantages in complex structure manufacturing, and realize the integrated manufacturing of structure and function. In this paper, a bearing cage with pentamode metamaterial structure was designed and fabricated by using selective laser sintering (SLS), and its deformation simulation and experimental tests were carried out. The results show that the 3D printed metamaterial structure cage has desired mechanical properties, and is workable in preliminary tests. Compared with the original commercial cage, the quality factor increased by one order of magnitude, which means it is easier to deform under shear force than pressure. This characteristic is beneficial to the high speed operation of rolling element bearings. In addition, due to its unique holes structure, its weight was reduced by 50% and more grease could be stored, resulting in a lower friction coefficient. When running steadily under the same condition, the power consumption of the bearing assembled with the 3D printed cage is 25% lower than that of the bearing assembled with the original cage. The study has demonstrated that 3D printed cages are of great research significance and broad application prospects.

Clostridium butyricum (C. butyricum) can provide many benefits for animals' growth performance and gut health. In this study, we investigated the effects of

Miscanthus, a perennial rhizomatous C4 grass, has emerged as a promising lignocellulosic crop. To avoid competition with food crops, marginal lands especially saline–alkaline soil are being recommended to grow Miscanthus across China. However, the challenges such as high cost and low reproduction coefficient associated with the propagation methods are impeding its large‐scale plantation in saline–alkaline soil. In this study, a “two‐steps” propagation method was designed, which was comprised of two phases: (1) seedling cultivation and (2) seedling strengthening. The parameters (substrate composition and plug size) for this method were determined. The optimal substrate composition of the seedling bed for M. sinensis, M. lutarioriparius, and their interspecific hybrids was peat and perlite at a ratio of 3:2, 3:1, and 3:3 by volume, respectively. The seedlings were transplanted into the plugs to deliver robust plantlets. The most appropriate plug size for M. sinensis, M. lutarioriparius, and their interspecific hybrids was 50 plugs (50 cm3/plug), 72 plugs (40 cm3/plug), and 72 plugs (40 cm3/plug), respectively. Three propagation methods, that is, direct sowing of seeds, rhizomes plantation, and “two‐steps” seed‐derived plugs for M. lutarioriparius were compared in saline–alkaline soil over 3 years (2014, 2015, and 2016). The establishment rate of the seeds directly planted was poor (zero). The performance (e.g., biomass yield) of the plants derived from the “two‐steps” seed‐derived plugs was better than that of the plants derived from rhizomes directly planted. Therefore, the “two‐steps” seed‐derived plugs can be regarded as an effective propagation method to upscale Miscanthus cultivation in saline–alkaline soil.

MicroRNA-363-3 p (miR-363–3 p) has been reported to play a crucial role in tumor development and progression, and function as a tumor suppressor in many types of cancer. In our previous studies, we found that miRNA-363–3 p inhibited papillary thyroid carcinoma (PTC) progression by targeting PIK3CA. Meanwhile, we found that NIN1/RPN12 binding protein 1 (NOB1) was significantly upregulated in thyroid carcinoma tissue and downregulation of NOB1 expression significantly inhibited cell proliferation, migration and invasion in PTC. However, the correlation of NOB1 and miR-363–3 p has not been investigated. Here, we performed bioinformatic analysis to explore miRNA targeting NOB1. We found that NOB1 was a target of miR-363–3 p and miR-363–3 p regulated NOB1 expression at the translational and transcriptional levels by targeting its 3’ untranslated region (3′-UTR). Further, we showed that miR-363–3 p inhibited tumor progression by targeting NOB1 in vitro and in vivo. We found that overexpression miR-363–3 p or silencing NOB1 significantly increased G0/G1-phase and decreased S-phase in the human papillary thyroid cells, which led to a significant delay in cell proliferation, indicating miR-363–3 p and NOB1 are crucial for human papillary thyroid cancer tumorigenesis. Collectively, our data unveil that miR-363–3 p negatively regulates NOB1 activity by reducing its stability. This study provides a new therapeutic target for regulation of NOB1 stability to modulate human papillary thyroid cancer progression.

BACKGROUND Diabetic nephropathy (DN) is the main cause of chronic kidney disease and end-stage renal disease worldwide. Although available clinical trials have shown that endothelin receptor (ER) antagonists may be a novel and beneficial drug for DN, no consistent conclusions regarding their sufficient effectiveness and safety for patients with DN have been presented. AIM To assess the effectiveness and safety of ER antagonists among patients with DN. METHODS The EMBASE, PubMed, MEDLINE, Cochrane, and ClinicalTrials.gov databases were searched without any language restrictions. Relative risks with 95% confidence intervals (CIs) for dichotomous data and mean differences or standardized mean difference with 95%CIs for continuous data were calculated using Review Manager 5.3 software. Publication bias was assessed using Egger’s test with Stata/SE software. RESULTS We enrolled seven studies with six data sets and 5271 participants. The ER antagonists group showed a significantly greater reduction in albuminuria and more patients with 40% reduction in urinary albumin-to-creatinine ratio than the control group (P < 0.0001 and P = 0.02, respectively). Subgroup analysis for reductions in estimated glomerular filtration rate (eGFR) showed that for the middle-dosage subgroup, the ER antagonists group exhibited lower eGFR reduction than the control group (P < 0.00001; mean difference, 0.70 95%CI: 0.66, 0.74). Moreover, significant reductions in systolic and diastolic blood pressure were observed in the invention group. CONCLUSION ER blockades combined with angiotensin converting enzyme inhibitor /angiotensin II type 1 receptor blockers may be an effective treatment to lower blood pressure and reduce proteinuria in DN with declined eGFR. However, attention should be given to adverse events, including cardiac failure, anemia, and hypoglycemia, as well as serious adverse events.

Dysfunctions of upper limbs caused by diseases such as stroke result in difficulties in conducting day-to-day activities. Studies show that rehabilitation training using virtual reality games is helpful for patients to restore arm functions. It has been found that ensuring active patient participation and effort devoting in the process is very important to obtain better training results. This article introduces a method to help patients increase their engagement and provide motion assistance in virtual reality-mediated upper-limb rehabilitation training. Attention enhancement and motion assistance is achieved through an illusion of virtual forces created by altering the drag speed between the cursor and the object presented on a screen to the patient as the only feedback. We present two game forms using the proposed method, including a target-approaching game and a maze-following game. The results of evaluation experiments with human participants showed that the proposed method could provide path guidance that significantly improved path-following performance of users and required more involvement of the users when compared to playing the game without attention enhancement and motion assistance.

Cultivating the dedicated biomass crop

BackgroundNatural killer (NK) cells play major roles in eliminating tumor cells. Preliminary studies have shown that NK cells and their receptors/ligands have prognostic value in malignant tumors. However, the relevance of NK cells and their receptors/ligands level to the prognosis of hepatocellular carcinoma (HCC) remains unclear.MethodsSeveral electronic databases were searched from database inception to November 8, 2021. Random effects were introduced to this meta-analysis. The relevance of NK cells and their receptors/ligands level to the prognosis of HCC was evaluated using hazard ratios (HRs) with 95% confidence interval (95%CI).Results26 studies were included in the analysis. The pooled results showed that high NK cells levels were associated with better overall survival (HR=0.70, 95%CI 0.57–0.86, P=0.001) and disease-free survival (HR=0.61, 95%CI 0.40-0.93, P=0.022) of HCC patients. In subgroup analysis for overall survival, CD57+ NK cells (HR=0.70, 95%CI 0.55-0.89, P=0.004) had better prognostic value over CD56+ NK cells (HR=0.69, 95%CI 0.38-1.25, P=0.224), and intratumor NK cells had better prognostic value (HR=0.71, 95%CI 0.55-0.90, P=0.005) over peripheral NK cells (HR=0.66, 95%CI 0.41-1.06, P=0.088). In addition, high level of NK cell inhibitory receptors predicted increased recurrence of HCC, while the prognostic role of NK cell activating receptors remained unclear.ConclusionNK cells and their inhibitory receptors have prognostic value for HCC. The prognostic role of NK cell activating receptors is unclear and more high-quality prospective studies are essential to evaluate the prognostic value of NK cells and their receptors/ligands for HCC.

As interference waves in deep reflection data processing, surface waves are often suppressed as noise, but surface waves carry considerable underground media information, including structural information and the physical properties of rocks. Reasonable extraction and use of surface wave signals are of great significance for studying the underground structure, regional velocity characteristics, and physical properties of rocks. The deep reflection data are collected using large offsets, trail spacing, and explosive sources. The surface wave energy tends to be stronger, and the high-frequency surface wave signal is abundant. After extraction and inversion, the shallow high-precision shear wave velocity structure can be obtained. Near the Cuonadong dome in the southern Tibet detachment system (STDS), a large number of leucogranites are developed in the core, containing important rare metal minerals and high metallogenic potential. However, the research degree is relatively low, especially for the shallow part. In this paper, we use deep reflection data from a profile through the Cuonadong dome to obtain the S-wave velocity structure of the shallow 0-1.5 km layer by extracting the surface wave fundamental-order dispersion curve and inversion. Combined with the regional geological and geomagnetic data, we explained the variation in the sedimentary layer thickness of the Cuonadong dome; speculate that there may be several hidden faults in the Cuonadong dome that extend shallowly; revealed the high-velocity anomaly and its characteristics under the Cuonadong dome. These understandings of the structure and velocity field of the Cuonadong dome can provide a powerful geophysical basis for establishing the dome structure model and searching for hidden ore bodies.

BackgroundThe relationship between baseline C-reactive protein (CRP) level and the prognosis of cancer patients receiving immune checkpoint inhibitor (ICI) treatment remains controversial. The aim of this meta-analysis was to clarify whether baseline CRP level can serve as a biomarker to predict the efficiency of ICI therapy.MethodsAll associated articles published in the Cochrane Library, EMBASE, and PubMed databases from the inception of the database to December 30, 2021, were retrieved. Progression-free survival (PFS) and overall survival (OS) outcomes were meta-analyzed using the random-effects model and adjusted using the trim-and-fill method because of publication bias.ResultsThirty-three studies (6,124 patients) conducted between 2013 and 2021 were identified. The pooled outcomes implied that high baseline CRP level patients had significantly worse OS (adjusted pooled value for univariate and multivariate analysis outcomes: HR = 1.48, 95% CI = 1.41–1.56; HR = 1.46, 95% CI = 1.34–1.59) and PFS (adjusted pooled value for univariate and multivariate analysis outcomes: HR = 1.29, 95% CI = 1.15–1.45; HR = 1.20, 95% CI = 1.02–1.40) than low baseline CRP level patients, irrespective of cancer or ICI type. Further analysis indicated that 1 mg/dl was appropriate as a cutoff value for determining the low or high level of baseline CRP to predict the OS or PFS of cancer patients receiving ICI treatment (univariate analysis: HR = 1.56, 95% CI = 1.24–1.97, P = 0.909; multivariate analysis: HR = 1.58, 95% CI = 1.23–2.03, P = 0.521).ConclusionsHigh baseline CRP level (>1 mg/dl) may be an indicator for worse OS and PFS of cancer patients treated with ICIs. More high-quality prospective studies are warranted to assess the predictive value of CRP for ICI treatment.