Predicting the prognosis of glioma by pyroptosis-related signature.

Glioma is the most common malignant primary brain tumour. It is of great significance for the prognosis and personalized treatment of glioma patients to accurate identification of glioma based on biomarkers. Pyroptosis, a kind of programmed cell death, is closely related to tumour progression and tumour immune microenvironment. However, the role of pyroptosis in glioma remained unclear. Herein, we used glioma clinical and expression data from TCGA and CGGA to explore the relationship between pyroptosis and glioma. We first summarized the incidence of copy number variations and somatic mutations of 33 pyroptosis-related genes and explored prognostic correlation of these genes. Based on pyroptosis-related genes, three molecular subgroups of glioma related to prognosis were identified. We also found that each subgroup has unique immune and biological behaviours characteristics. Finally, based on 7 pyroptosis-related genes (CASP3, CASP4, CASP6, CASP8, CASP9, PRKACA and ELANE), we constructed a prognosis model by Lasso and Cox regression, which had a strong predictive power for the overall survival in CGGA test cohort (p < 0.05). In summary, we explored the role of pyroptosis-related genes in gliomas and the association of these genes with tumour immunity. We found the biomarkers valuable to diagnosis and prognosis, hence, provide reference to the development and treatment of tumorigenesis in glioma.

LIBRETTO-432, a phase III study of adjuvant selpercatinib or placebo in stage IB-IIIA RET fusion-positive non-small-cell lung cancer.

Selpercatinib, a first-in-class, highly selective and potent central nervous system-active RET kinase inhibitor demonstrated clinically meaningful activity with manageable toxicity in pretreated and treatment-naive advanced/metastatic RET fusion-positive non-small-cell lung cancer (NSCLC). LIBRETTO-432 is a global, randomized, double-blind, phase III trial evaluating selpercatinib versus placebo in stage IB-IIIA, RET fusion-positive NSCLC, previously treated with definitive surgery or radiation; participants must have undergone available anti-cancer therapy (including chemotherapy or durvalumab) or not be suitable for it, per investigator's discretion. The primary end point is investigator-assessed event-free survival (EFS) in the primary analysis population (stage II-IIIA RET fusion-positive NSCLC). Key secondary end points include EFS in the overall population, overall survival, and time to distant disease recurrence in the central nervous system.

Selpercatinib is approved in multiple countries for the treatment of advanced or metastatic RET-altered lung cancers. Selpercatinib has shown promising efficacy and safety results in patients with advanced/metastatic RET fusion-positive NSCLC. This is a summary of the LIBRETTO-432 study which compares selpercatinib with placebo in patients with earlier stages (stage IB-IIIA) of RET fusion-positive NSCLC, who have already undergone surgery or radiotherapy and applicable adjuvant chemotherapy. This study is active and currently recruiting new participants. This trial will evaluate how long people live without evidence of cancer recurrence, both during and after treatment. Side effects will also be evaluated in this study. Clinical Trial Registration: NCT04819100 (ClinicalTrials.gov).

Effect of starch-derived organic acids on the removal of polycyclic aromatic hydrocarbons in an aquaculture-sediment microbial fuel cell.

This study constructed sediment microbial fuel cells (SMFCs) for polycyclic aromatic hydrocarbons (PAHs) removal in contaminated aquaculture sediment. Starch, a waste deposited in aquaculture sediment, was employed as the co-substrate for electricity generation and PAHs removal, and the effect of starch-derived organic acids on SMFC performance was assessed. The results indicated that sufficient starch promoted PAHs removal (69.9% for naphthalene, 55.6% for acenaphthene, and 46.8% for pyrene) in dual-chamber SMFC, whereas excessive starch attenuated SMFC performance because the organic acids accumulation reduced anode pH, decreased species diversity, and changed the microbial communities. The electricity generation and PAHs removal were positively correlated (R > 0.96), and both of them were related to Macellibacteroides belonging to Bacteroidetes. However, a larger single-chamber SMFC device did not obtain enhanced PAHs removal owing to the restricted "effective range" of the anode. Hence, more challenges need to be addressed to realize the practical application of SMFC.

Impact of input field characteristics on vibrational femtosecond coherent anti-Stokes Raman scattering thermometry.

In this paper, three ultrashort-pulse coherent anti-Stokes Raman scattering (CARS) thermometry approaches are summarized with a theoretical time-domain model. The difference between the approaches can be attributed to variations in the input field characteristics of the time-domain model. That is, all three approaches of ultrashort-pulse (CARS) thermometry can be simulated with the unified model by only changing the input fields features. As a specific example, the hybrid femtosecond/picosecond CARS is assessed for its use in combustion flow diagnostics; thus, the examination of the input field has an impact on thermometry focuses on vibrational hybrid femtosecond/picosecond CARS. Beginning with the general model of ultrashort-pulse CARS, the spectra with different input field parameters are simulated. To analyze the temperature measurement error brought by the input field impacts, the spectra are fitted and compared to fits, with the model neglecting the influence introduced by the input fields. The results demonstrate that, however the input pulses are depicted, temperature errors still would be introduced during an experiment. With proper field characterization, however, the significance of the error can be reduced.

Design, synthesis and evaluation of antitumor acylated monoaminopyrroloquinazolines.

Pyrroloquinazoline is a privileged chemical scaffold with diverse biological activities. We recently described a series of N-3 acylated 1,3-diaminopyrroloquinazolines with potent anticancer activities. The N-1 primary amino group in 1,3-diaminopyrroloquinazoline is critical for its inhibitory activity against dihydrofolate reductase (DHFR). In order to design out this unnecessary DHFR inhibition activity and further expand the chemical space associated with pyrroloquinazoline, we removed the N-1 primary amino group. In this report, we describe our design and synthesis of a series of N-3 acylated monoaminopyrroloquinazolines. Biological evaluation of these compounds identified a naphthamide 4a as a potent anticancer agent (GI50=88-200nM), suggesting that removing the N-1 primary amino group in 1,3-diaminopyrroloquinazoline is a useful chemical modification that can be introduced to improve the anticancer activity.

Synthesis and in vitro cytotoxic evaluation of new 1H-benzo[d]imidazole derivatives of dehydroabietic acid.

A series of new 1H-benzo[d]imidazole derivatives of dehydroabietic acid were designed and synthesized as potent antitumor agents. Structures of the target molecules were characterized using MS, IR, 1H NMR, 13C NMR and elemental analyses. In the in vitro cytotoxic assay, most compounds showed significant cytotoxic activities against two hepatocarcinoma cells (SMMC-7721 and HepG2) and reduced cytotoxicity against noncancerous human hepatocyte (LO2). Among them, compound 7b exhibited the best cytotoxicity against SMMC-7721 cells (IC50: 0.36±0.13µM), while 7e was most potent to HepG2 cells (IC50: 0.12±0.03µM). The cell cycle analysis indicated that compound 7b caused cell cycle arrest of SMMC-7721 cells at G2/M phase. Further, compound 7b also induced the apoptosis of SMMC-7721 cells in Annexin V-APC/7-AAD binding assay.

Synthesis and cytotoxic activity of novel tetrahydrobenzodifuran-imidazolium salt derivatives.

The synthesis of a series of novel 4-substituted 2,3,6,7-tetrahydrobenzo [1,2-b;4,5-b']difuran-1H-imidazolium salts is presented. The biological properties of the compounds were evaluated in vitro against a panel of human tumor cell lines. Results suggest that the 5,6-dimethyl-benzimidazole or 2-methyl-benzimidazole ring, and substitution of the imidazolyl-3-position with a 2-naphthylmethyl substituent or 2-naphthylacyl substituent, were important to the cytotoxic activity. Notably, 3-(2-Naphthylmethyl)-1-((2,3,6,7-tetrahydrobenzo[1,2-b;4,5-b']difuran-4-yl)methyl)-1H-5,6-dimethyl-benzimidazol-3-ium bromide (42) was found to be the most potent derivative against five human tumor cell lines with IC50 values of 1.06-4.34µM and more selective towards SMMC-7721, A549 and SW480 cell lines. 3-(2-Naphthylacyl)-1-((2,3,6,7-tetrahydrobenzo[1,2-b;4,5-b']difuran-4-yl)methyl)-1H-2-methyl-benzimidazol-3-ium bromide (37) showed higher selectivity to SMMC-7721 and MCF-7 cell lines with IC50 values 2.7-fold and 8.4-fold lower than DDP. Study regarding to the antitumor mechanism of action showed that compound 37 could induce cell cycle G1 phase arrest and apoptosis in SMMC-7721 cells.

Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: a single-group, multicentre, phase 2 trial.

BACKGROUND: Alectinib--a highly selective, CNS-active, ALK inhibitor-showed promising clinical activity in crizotinib-naive and crizotinib-resistant patients with ALK-rearranged (ALK-positive) non-small-cell lung cancer (NSCLC). We aimed to assess the safety and efficacy of alectinib in patients with ALK-positive NSCLC who progressed on previous crizotinib. METHODS: We did a phase 2 study at 27 centres in the USA and Canada. We enrolled patients aged 18 years or older with stage IIIB-IV, ALK-positive NSCLC who had progressed after crizotinib. Patients were treated with oral alectinib 600 mg twice daily until progression, death, or withdrawal. The primary endpoint was the proportion of patients achieving an objective response by an independent review committee using Response Evaluation Criteria in Solid Tumors, version 1.1. Response endpoints were assessed in the response-evaluable population (ie, patients with measurable disease at baseline who received at least one dose of study drug), and efficacy and safety analyses were done in the intention-to-treat population (all enrolled patients). This study is registered with ClinicalTrials.gov, number NCT01871805. The study is ongoing and patients are still receiving treatment. FINDINGS: Between Sept 4, 2013, and Aug 4, 2014, 87 patients were enrolled into the study (intention-to-treat population). At the time of the primary analysis (median follow-up 4·8 months [IQR 3·3-7·1]), 33 of 69 patients with measurable disease at baseline had a confirmed partial response; thus, the proportion of patients achieving an objective response by the independent review committee was 48% (95% CI 36-60). Adverse events were predominantly grade 1 or 2, most commonly constipation (31 [36%]), fatigue (29 [33%]), myalgia 21 [24%]), and peripheral oedema 20 [23%]). The most common grade 3 and 4 adverse events were changes in laboratory values, including increased blood creatine phosphokinase (seven [8%]), increased alanine aminotransferase (five [6%]), and increased aspartate aminotransferase (four [5%]). Two patients died: one had a haemorrhage (judged related to study treatment), and one had disease progression and a history of stroke (judged unrelated to treatment). INTERPRETATION: Alectinib showed clinical activity and was well tolerated in patients with ALK-positive NSCLC who had progressed on crizotinib. Therefore, alectinib could be a suitable treatment for patients with ALK-positive disease who have progressed on crizotinib. FUNDING: F Hoffmann-La Roche.

Oncolytic reovirus in combination with chemotherapy in metastatic or recurrent non-small cell lung cancer patients with KRAS-activated tumors.

BACKGROUND: The type 3 Dearing reovirus (Reolysin) is a naturally occurring virus that preferentially infects and causes oncolysis in tumor cells with a Ras-activated pathway. It induces host immunity and cell cycle arrest and acts synergistically with cytotoxic agents. METHODS: This study evaluated Reolysin combined with paclitaxel and carboplatin in patients with metastatic/recurrent KRAS-mutated or epidermal growth factor receptor (EGFR)-mutated/amplified non-small cell lung cancer. RESULTS: Thirty-seven patients were treated. Molecular alterations included 20 KRAS mutations, 10 EGFR amplifications, 3 EGFR mutations, and 4 BRAF-V600E mutations. In total, 242 cycles (median, 4; range, 1-47) were completed. The initial doses were area under the curve (AUC) 6 mg/mL/min for carboplatin, 200 mg/m(2) for paclitaxel on day 1, and 3 × 10(10) 50% tissue culture infective dose for Reolysin on days 1 to 5 of each 21-day cycle. Because of diarrhea and febrile neutropenia (in the first 2 patients), subsequent doses were reduced to 175 mg/m(2) for paclitaxel and AUC 5 mg/mL/min for carboplatin. Toxicities included fatigue, diarrhea, nausea/vomiting, neutropenia, arthralgia/myalgia, anorexia, and electrolyte abnormalities. Response Evaluation Criteria in Solid Tumors 1.0 responses included the following: partial response for 11 patients, stable disease (SD) for 20 patients, progressive disease for 4 patients, and not evaluable for 2 patients (objective response rate, 31%; 90% 1-sided lower confidence interval, 21%). Four SD patients had >40% positron emission tomography standardized uptake value reductions. The median progression-free survival, median overall survival, and 12-month overall survival rate were 4 months, 13.1 months, and 57%, respectively. Seven patients were alive after a median follow-up of 34.2 months; they included 2 patients without disease progression at 37 and 50 months. CONCLUSIONS: Reolysin in combination with paclitaxel and carboplatin was well tolerated. The observed response rate suggests a benefit of the reovirus for chemotherapy. A follow-up randomized study is recommended. The proportion of patients surviving longer than 2 years (30%) suggests a second/third-line treatment effect or possibly the triggering of an immune response after tumor reovirus infiltration.

Novel CHOP activator LGH00168 induces necroptosis in A549 human lung cancer cells via ROS-mediated ER stress and NF-κB inhibition.

AIM: C/EBP homologous protein (CHOP) is a transcription factor that is activated at multiple levels during ER stress and plays an important role in ER stress-induced apoptosis. In this study we identified a novel CHOP activator, and further investigated its potential to be a therapeutic agent for human lung cancer. METHODS: HEK293-CHOP-luc reporter cells were used in high-throughput screening (HTS) to identify CHOP activators. The cytotoxicity against cancer cells in vitro was measured with MTT assay. The anticancer effects were further examined in A549 human non-small cell lung cancer xenograft mice. The mechanisms underlying CHOP activation were analyzed using luciferase assays, and the anticancer mechanisms were elucidated in A549 cells. RESULTS: From chemical libraries of 50 000 compounds, LGH00168 was identified as a CHOP activator, which showed cytotoxic activities against a panel of 9 cancer cell lines with an average IC50 value of 3.26 µmol/L. Moreover, administration of LGH00168 significantly suppressed tumor growth in A549 xenograft bearing mice. LGH00168 activated CHOP promoter via AARE1 and AP1 elements, increased DR5 expression, decreased Bcl-2 expression, and inhibited the NF-κB pathway. Treatment of A549 cells with LGH00168 (10 µmol/L) did not induce apoptosis, but lead to RIP1-dependent necroptosis, accompanied by cell swelling, plasma membrane rupture, lysosomal membrane permeabilization, MMP collapse and caspase 8 inhibition. Furthermore, LGH00168 (10 and 20 µmol/L) dose-dependently induced mito-ROS production in A549 cells, which was reversed by the ROS scavenger N-acetyl-L-cysteine (NAC, 10 mmol/L). Moreover, NAC significantly diminished LGH00168-induced CHOP activation, NF-κB inhibition and necroptosis in A549 cells. CONCLUSION: LGH00168 is a CHOP activator that inhibits A549 cell growth in vitro and lung tumor growth in vivo.

[Temperature Measurement of CH4/Air Premix Flat Flame Based on the Absorption Spectroscopy Technology of UV Tunable Laser].

The physics of combusting flows consists of a complex interaction between chemical reactions, fluid mechanics and radiation. Temperature is one of the most important parameters for the processes. Laser-based imaging techniques are frequently used to assess temperature information from reactive systems without perturbing the system under study. To verify the feasibility of the temperature measurement of UV tunable absorption spectroscopy technology the methane/air premix flat flame was selected as the target of test because of the combustion stability of this kind of flame. Before the temperature measurement the distribution of OH radical in the premix flat flame under different operating conditions were obtained by using planar laser induced fluorescence (PLIF). At the low equivalence ratio the OH radicals distribute uniformly in the flame for the adequate oxygen in the premix gas. The condition with uniform distribution of OH in the flame was selected for the UV tunable absorption spectroscopy measurement. For the selection of absorption lines of the measurement the spectrum of OH A-X(0,0) band have been simulated by LIFBASE. Considering the slope sensitivity and SNR of the test the transitions P1(2) and Q1(8) were suitable for the temperature measurement of the flame. A dye laser pumped by a frequency doubled Nd:YAG laser was used to generated the UV laser. The dye laser was operated with the mixed dye of DCM and PM580 for high conversion efficiency at 310 nm. To investigate the transitions of Q1(8) and P1(2) of OH A-X(0,0) the laser was tuned from 309.225~309.255 and 308.625~308.655 nm separately with the step of 0.4 pm, 30 pulses were recorded at each step. The laser pulses reflected by the beam splitter were collected by detector A, and the pulses passed the flame were collected by detector B. The signal of these two detectors were recorded by the oscilloscope and acquired by the computer automatically. The line shape of these transitions can be obtained after fitting the experimental data with the Voigt function. The integral ratio between the fitting results of these two lines was calculated. Then temperature of the flame could be deduced by the integral ratio. The temperatures of different positions above the surface of burner and varied heights of the flame center were obtained by measuring the integrated absorption ratio of these two transitions. The test results of this method are compared with the report in reference, in which temperature of the burner with the same structure was measured by other ways. The results of these two tests agree well. It shows that this method has the potential to be a calibration for the two-dimension thermometry in flame such as two-line PLIF.

Cholelithiasis and the risk of intrahepatic cholangiocarcinoma: a meta-analysis of observational studies.

BACKGROUND: The etiological factor for intrahepatic cholangiocarcinoma (ICC) is not clear. Although it has been widely accepted that intrahepatic biliary tree stone is associated with increased risk of ICC, the role of extrahepatic biliary tree stone in the incidence of ICC is controversial. In the present study we aim to evaluate the association between pre-existing choledocholithiasis and cholecystolithiasis and the risk of ICC. METHODS: PubMed, Embase, and Web of Science were searched to identify cohort and case-control studies on the association between choledocholithiasis or cholecystolithiasis and the risk of ICC. Studies that met the inclusion criteria were subjected to a meta-analysis performed with Stata statistical software. Either a fixed or random effect model was used, depending on the heterogeneity within the studies. Egger's test was performed to assess publication bias. RESULTS: Seven case-control studies met our inclusion criteria. Of the 123,771 participants, 4763 (3.85 %) were patients with ICC, and 119,008 were tumor-free controls. The presence of pre-existing bile duct stones (choledocholithiasis alone or choledocholithiasis accompanied by hepatolithiasis) was associated with the risk of ICC (odds ratio [OR] 17.64, 95 % confidence interval [CI] 11.14-27.95). Even the presence of choledocholithiasis alone (in the absence of hepatolithiasis) was associated with a high risk of ICC (OR 11.79, 95 % CI 4.17-33.35). Cholecystolithiasis may possibly contributed to the incidence of ICC (OR 2.00, 95 % CI 1.16-3.42), with large heterogeneity within studies (I (2) = 78.5 %). CONCLUSIONS: Bile duct stones including choledocholithiasis are important risk factors for ICC. Careful surveillance of patients with extrahepatic biliary tree stone should be considered.

[Research on Real-Time Trace Gas Detection System Based on QEPAS].

Quartz-enhanced photoacoustic spectroscopy (QEPAS) technology was invented lately. Therefore it's an innovative method for trace gas detection compared with other existed technologies. In this paper, we studied the trace gas detection system based on QEPAS, and the atmospheric H2O was selected as the target analyte. In theory, the principles of laser wavelength modulation and signal harmonic detection were analyzed firstly, and the realizing solutions for the gas concentration retrieving and laser wavelength locking were obtained. Furthermore, the selection principle of absorption line for high sensitivity gas detection was discussed. In experiments, a continuous-wave distributed feedback(DFB) single mode diode laser emitting at 1.39 µm was used as the exciting source for the H2O vapor measurement. Using wavelength modulation spectroscopy and 2nd harmonic detection, the influence of laser wavelength modulation depth on QEPAS signal level was investigated, and the acoustic wave enhancement of the addition of micro-resonator in the acoustic detection module was analyzed as well. After optimization of the QEPAS system, a detection limit of 5.9 ppm for H2O vapor was obtained. We measured the H2O vapor with different concentrations, and the R-Square of 0.98 was achieved after the experimental data was linear fitted, indicated that the QEPAS system had an excellent linear response ability. Finally, continuous monitoring of atmospheric H2O concentration levels for a period of 12 hours was performed when the line locking mode was employed with the help of 3rd harmonic detection. The experimental results showed that this QEPAS scheme had a stable performance and outstanding continuous measuring capacity, and it can be widely used in high sensitivity on-line measurement for other trace gases detection fields.

[3-D fluorescence properties of river with great flow rate].

In the present study, the three-dimensional fluorescence spectra of River A with great flow rate were investigated. The results showed that there existed three unambiguous peaks in the excitation-emission matrix of River A at lambda(ex)/lambda(em) of around 230/340, 280/320 and 250/450 nm respectively. The fluorescence intensity varied significantly and had sharp fluctuation sometimes. But the COD(Mn) of the samples remained quite stable. This study indicated that fluorescence technique could demonstrate the pollution in the water bodies with great flow rate and furthermore make up for the deficiency of the conventional parameters related to organic pollution, i. e. invalidation to exhibit the components of pollutants. It is a good tool for the early-warning of the water quality.

CG-SLENP: A Chemical Genetics Strategy To Selectively Label Existing Proteins and Newly Synthesized Proteins.

Protein synthesis and subsequent delivery to the target locations in cells are essential for their proper functions. Methods to label and distinguish newly synthesized proteins from existing ones are critical to assess their differential properties, but such methods are lacking. We describe the first chemical genetics-based approach for selective labeling of existing and newly synthesized proteins that we termed as CG-SLENP. Using HaloTag in-frame fusion with lamin A (LA), we demonstrate that the two pools of proteins can be selectively labeled using CG-SLENP in living cells. We further employ our recently developed selective small molecule ligand LBL1 for LA to probe the potential differences between newly synthesized and existing LA. Our results show that LBL1 can differentially modulate these two pools of LA. These results indicate that the assembly states of newly synthesized LA are distinct from existing LA in living cells. The CG-SLENP method is potentially generalizable to study any cellular proteins.

Epidemiology and survival of patients with spinal meningiomas: a large retrospective cohort study.

INTRODUCTION: Spinal meningiomas (SMs) are relatively rare central nervous system tumors that usually trigger neurological symptoms. The prevalence of SMs is increasing with the aging of the global population. This study aimed to perform a systematic epidemiologic and survival prognostic analysis of SMs to evaluate their public health impact and to develop a novel method to estimate the overall survival at 3-year, 5-year, and 10-year in patients with SMs. METHODS: Five thousand one hundred fifty eight patients with SMs were recruited from the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2019. Firstly, descriptive analysis was performed on the epidemiology of SMs. Secondly, these individuals were randomly allocated to the training and validation sets in a ratio of 7:3. Kaplan-Meier method and Cox regression analysis were utilized in the training set to identify independent prognostic factors and to construct a nomogram for survival prognosis. Subsequently, the discriminative power, predictive performance, and clinical utility of the nomogram were evaluated by receiver operating characteristic curve and decision curve analysis. Finally, a mortality risk stratification system and a web-based dynamic nomogram were constructed to quantify the risk of mortality in patients with SMs. RESULTS: The annual age-adjusted incidence rates of SMs increased steadily since 2004, reaching a rate of 0.40 cases per 100 000 population in 2019, with a female-to-male ratio of ~4:1. The age groups of 50-59, 60-69, and 70-79 years old were the most prevalent ages for SMs, accounting for 19.08, 24.93, and 23.32%, respectively. In addition, seven independent prognostic factors were identified to establish a prognostic nomogram for patients with SMs. The decision curve analysis and receiver operating characteristic curve indicated that the nomogram had high clinical utility and favorable accuracy. Moreover, the mortality risk stratification system effectively divided patients into low-risk, middle-risk, and high-risk subgroups. CONCLUSIONS: SMs are relatively rare benign spinal tumors prevalent in the white elderly female population. Clinicians could use the nomogram to personalize the prediction of the overall survival probability of patients with SMs, categorize these patients into different mortality risk subgroups, and develop personalized decision-making plans. Moreover, the web-based dynamic nomogram could help to further promote clinical application and assist clinicians in providing personalized counseling, timely monitoring, and clinical assessment for patients.

Advanced tumor organoid bioprinting strategy for oncology research.

Bioprinting is a groundbreaking technology that enables precise distribution of cell-containing bioinks to construct organoid models that accurately reflect the characteristics of tumors in vivo. By incorporating different types of tumor cells into the bioink, the heterogeneity of tumors can be replicated, enabling studies to simulate real-life situations closely. Precise reproduction of the arrangement and interactions of tumor cells using bioprinting methods provides a more realistic representation of the tumor microenvironment. By mimicking the complexity of the tumor microenvironment, the growth patterns and diffusion of tumors can be demonstrated. This approach can also be used to evaluate the response of tumors to drugs, including drug permeability and cytotoxicity, and other characteristics. Therefore, organoid models can provide a more accurate oncology research and treatment simulation platform. This review summarizes the latest advancements in bioprinting to construct tumor organoid models. First, we describe the bioink used for tumor organoid model construction, followed by an introduction to various bioprinting methods for tumor model formation. Subsequently, we provide an overview of existing bioprinted tumor organoid models.

Advanced topology of triply periodic minimal surface structure for osteogenic improvement within orthopedic metallic screw.

Metallic screws are one of the most common implants in orthopedics. However, the solid design of the screw has often resulted in stress shielding and postoperative loosening, substantially impacting its long-term fixation effect after surgery. Four additive manufacturing porous structures (Fischer-Koch S, Octet, Diamond, and Double Gyroid) are now introduced into the screw to fix those issues. Upon applying the four porous structures, elastic modulus in the screw decreased about 2∼15 times to reduce the occurrence of stress shielding, and bone regeneration effect on the screw surface increased about 1∼50 times to improve bone tissue regrowing. With more bone tissue regrowing on the inner surface of porous screw, a stiffer integration between screw and bone tissue will be achieved, which improves the long-term fixation of the screw tremendously. The biofunctions of the four topologies on osteogenesis have been fully explored, which provides an advanced topology optimization scheme for the screw utilized in orthopedic fixation.

Identification and Validation of a Novel Tertiary Lymphoid Structures-Related Prognostic Gene Signature in Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors originating from the digestive system. Tertiary lymphoid structures (TLS), non-lymphoid tissues outside of the lymphoid organs, are closely connected to chronic inflammation and tumorigenesis. However, the detailed relationship between TLS and HCC prognosis remained unclear. In this study, we aimed to construct a TLS-related gene signature for predicting the prognosis of HCC patients. Methods: The Cancer Genome Atlas (TCGA) clinical data from 369 HCC tissues and 50 normal liver tissues were utilized to examine the differential expression of TLS-related genes. Based on least absolute shrinkage and selection operator (LASSO) Cox regression analysis, the prognostic model was constructed using the TCGA cohort and validated in the GSE14520 cohort and International Cancer Genome Consortium (ICGC) cohort. The Kaplan-Meier (KM) and receiver operating characteristic (ROC) curves were employed to validate the predictive ability of the prognostic model. Furthermore, Cox regression analysis was applied to identify whether the TLS score could be employed as an independent prognosis factor. A nomogram was developed to predict the survival probability of HCC patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed for TLS-related genes. Genetic mutation analysis, the CIBERSORT algorithm, and single-sample gene set enrichment analysis (ssGSEA) were used to assess the tumor mutation landscape and immune infiltration. Finally, the role of the TLS score in HCC therapy was investigated. Results: Six genes were included in the construction of our prognostic model (CETP, DNASE1L3, PLAC8, SKAP1, C7, and VNN2), and we validated its accuracy. Survival analysis showed that patients in the high-TLS score group had a significantly better overall survival than those in the low-TLS score group. Univariate, multivariate Cox regression analysis and the establishment of a nomogram indicated that the TLS score could independently function as a potential prognostic marker. A significant association between TLS score and immunity was revealed by an analysis of gene alterations and immune cell infiltration. In addition, two subtypes of the TLS score could accurately predict the effectiveness of sorafenib, transcatheter arterial chemoembolization (TACE), and immunotherapy in HCC patients. Conclusion: In this research, we conducted and validated a prognostic model associated with TLS that may be helpful for predicting clinical outcomes and treatment responsiveness for HCC patients.

Genetic diversity and prevalence of emerging Rickettsiales in Yunnan Province: a large-scale study.

BACKGROUND: Rickettsia and related diseases have been identified as significant global public health threats. This study involved comprehensive field and systematic investigations of various rickettsial organisms in Yunnan Province. METHODS: Between May 18, 2011 and November 23, 2020, field investigations were conducted across 42 counties in Yunnan Province, China, encompassing small mammals, livestock, and ticks. Preliminary screenings for Rickettsiales involved amplifying the 16S rRNA genes, along with additional genus- or species-specific genes, which were subsequently confirmed through sequencing results. Sequence comparisons were carried out using the Basic Local Alignment Search Tool (BLAST). Phylogenetic relationships were analyzed using the default parameters in the Molecular Evolutionary Genetics Analysis (MEGA) program. The chi-squared test was used to assess the diversities and component ratios of rickettsial agents across various parameters. RESULTS: A total of 7964 samples were collected from small mammals, livestock, and ticks through Yunnan Province and submitted for screening for rickettsial organisms. Sixteen rickettsial species from the genera Rickettsia, Anaplasma, Ehrlichia, Neoehrlichia, and Wolbachia were detected, with an overall prevalence of 14.72%. Among these, 11 species were identified as pathogens or potential pathogens to humans and livestock. Specifically, 10 rickettsial organisms were widely found in 42.11% (24 out of 57) of small mammal species. High prevalence was observed in Dremomys samples at 5.60%, in samples from regions with latitudes above 4000 m or alpine meadows, and in those obtained from Yuanmou County. Anaplasma phagocytophilum and Candidatus Neoehrlichia mikurensis were broadly infecting multiple genera of animal hosts. In contrast, the small mammal genera Neodon, Dremomys, Ochotona, Anourosorex, and Mus were carrying individually specific rickettsial agents, indicating host tropism. There were 13 rickettsial species detected in 57.14% (8 out of 14) of tick species, with the highest prevalence (37.07%) observed in the genus Rhipicephalus. Eight rickettsial species were identified in 2375 livestock samples. Notably, six new Rickettsiales variants/strains were discovered, and Candidatus Rickettsia longicornii was unambiguously identified. CONCLUSIONS: This large-scale survey provided further insight into the high genetic diversity and overall prevalence of emerging Rickettsiales within endemic hotspots in Yunnan Province. The potential threats posed by these emerging tick-borne Rickettsiales to public health warrant attention, underscoring the need for effective strategies to guide the prevention and control of emerging zoonotic diseases in China.