The potential protective role of Parkinson's disease against hypothyroidism: co-localisation and bidirectional Mendelian randomization study.

Background: The association between hypothyroidism and Parkinson's disease (PD) has sparked intense debate in the medical community due to conflicting study results. A better understanding of this association is crucial because of its potential implications for both pathogenesis and treatment strategies. Methods: To elucidate this complex relationship, we used Bayesian co-localisation (COLOC) and bidirectional Mendelian randomization (MR) analysis. COLOC was first used to determine whether hypothyroidism and PD share a common genetic basis. Subsequently, genetic variants served as instrumental variables in a bidirectional MR to explore causal interactions between these conditions. Results: COLOC analysis revealed no shared genetic variants between hypothyroidism and PD, with a posteriori probability of hypothesis 4 (PPH4) = 0.025. Furthermore, MR analysis indicated that hypothyroidism does not have a substantial causal effect on PD (OR = 0.990, 95% CI = 0.925, 1.060, p = 0.774). Conversely, PD appears to have a negative causal effect on hypothyroidism (OR = 0.776, 95% CI = 0.649, 0.928, p = 0.005). Conclusion: Our findings suggest the absence of shared genetic variants between hypothyroidism and PD. Interestingly, PD may inversely influence the risk of developing hypothyroidism, a finding that may inform future research and clinical approaches.

HMGN1 loss sensitizes lung cancer cells to chemotherapy.

The high mobility group nucleosome binding (HMGN) family, constitutes a large family of non-histone protein family known to bind the acidic patch of the nucleosomes with various key cellular functions. Several studies have highlighted the pivotal roles of HMGNs in the pathogenic process of various cancer types. However, the roles of HMGN family in lung adenocarcinoma (LUAD) have not been fully elucidated. Herein, integrative analyses of multiple-omics data revealed that HMGNs frequently exhibit dysregulation in LUAD. Subsequent analysis of the clinical relevance of HMGN1 demonstrated its association with poor prognosis in LUAD and its potential as a diagnostic marker to differentiate LUAD from healthy controls. Additionally, functional enrichment analysis suggested that HMGN1 was mainly involved in DNA repair. To corroborate these findings, cellular experiments were conducted, confirming HMGN1's crucial involvement in homologous recombination repair and its potential to enhance the sensitivity of LUAD cells to standard chemotherapeutic drugs. This study proposes HMGN1 as a novel prognostic biomarker and a promising target for chemotherapy in lung adenocarcinoma.

Insights into the hydrogen generation and catalytic mechanism on Co-based nanocomposites derived from pyrolysis of organic metal precursor.

Hydrogen generation from boron hydride is important for the development of hydrogen economy. Cobalt (Co) element has been widely used in the hydrolysis of boron hydride. Pyrolysis is a common method for materials synthesis in catalytic fields. Herein, Co-based nanocomposites derived from the pyrolysis of organic metal precursors and used for hydrolysis of boron hydride are summarized and discussed. The different precursors consisting of MOF, supported, metal, and metal phosphide precursors are summarized. The catalytic mechanism consisting of dissociation mechanism based on oxidative addition-reduction elimination, pre-activation mechanism, SN2 mechanism, four-membered ring mechanism, and acid-base mechanism is intensively discussed. Finally, conclusions and outlooks are conveyed from the design of high-efficiency catalysts, the characterization of catalyst structure, the enhancement of catalytic activities, the investigation of the catalytic mechanism, and the catalytic stability of active structure. This review can provide guidance for designing high-efficiency catalysts and boosting development of hydrogen economy.

Chemical Compositions of Scutellaria baicalensis Georgi. (Huangqin) Extracts and Their Effects on ACE2 Binding of SARS-CoV-2 Spike Protein, ACE2 Activity, and Free Radicals.

The water and ethanol extracts of huangqin, the roots of Scutellaria baicalensis Georgi. with potential antiviral properties and antioxidant activities, were investigated for their chemical profiles and their abilities to interfere with the interaction between SARS-CoV-2 spike protein and ACE2, inhibiting ACE2 activity and scavenging free radicals. A total of 76 compounds were tentatively identified from the extracts. The water extract showed a greater inhibition on the interaction between SARS-CoV-2 spike protein and ACE2, but less inhibition on ACE2 activity than that of the ethanol extract on a per botanical weight concentration basis. The total phenolic content was 65.27 mg gallic acid equivalent (GAE)/g dry botanical and the scavenging capacities against HO●, DPPH●, and ABTS●+ were 1369.39, 334.37, and 533.66 µmol trolox equivalent (TE)/g dry botanical for the water extract, respectively. These values were greater than those of the ethanol extract, with a TPC of 20.34 mg GAE/g, and 217.17, 10.93, and 50.21 µmol TE/g against HO●, DPPH●, and ABTS●+, respectively. The results suggested the potential use of huangqin as a functional food ingredient in preventing COVID-19.

Review and perspectives on TS-1 catalyzed propylene epoxidation.

Titanium silicate zeolite (TS-1) is widely used in the research on selective oxidations of organic substrates by H2O2. Compared with the chlorohydrin process and the hydroperoxidation process, the TS-1 catalyzed hydroperoxide epoxidation of propylene oxide (HPPO) has advantages in terms of by-products and environmental friendliness. This article reviews the latest progress in propylene epoxidation catalyzed by TS-1, including the HPPO process and gas phase epoxidation. The preparation and modification of TS-1 for green and sustainable production are summarized, including the use of low-cost feedstocks, the development of synthetic routes, strategies to enhance mass transfer in TS-1 crystal and the enhancement of catalytic performance after modification. In particular, this article summarizes the catalytic mechanisms and advanced characterization techniques for propylene epoxidation in recent years. Finally, the present situation, development prospect and challenge of propylene epoxidation catalyzed by TS-1 were prospected.

Biomass-Derived Catalytically Active Carbon Materials for the Air Electrode of Zn-air Batteries.

Given the growing environmental and energy problems, developing clean, renewable electrochemical energy storage devices is of great interest. Zn-air batteries (ZABs) have broad prospects in energy storage because of their high specific capacity and environmental friendliness. The unavailability of cheap air electrode materials and effective and stable oxygen electrocatalysts to catalyze air electrodes are main barriers to large-scale implementation of ZABs. Due to the abundant biomass resources, self-doped heteroatoms, and unique pore structure, biomass-derived catalytically active carbon materials (CACs) have great potential to prepare carbon-based catalysts and porous electrodes with excellent performance for ZABs. This paper reviews the research progress of biomass-derived CACs applied to ZABs air electrodes. Specifically, the principle of ZABs and the source and preparation method of biomass-derived CACs are introduced. To prepare efficient biomass-based oxygen electrocatalysts, heteroatom doping and metal modification were introduced to improve the efficiency and stability of carbon materials. Finally, the effects of electron transfer number and H2 O2 yield in ORR on the performance of ZABs were evaluated. This review aims to deepen the understanding of the advantages and challenges of biomass-derived CACs in the air electrodes of ZABs, promote more comprehensive research on biomass resources, and accelerate the commercial application of ZABs.

CoP/Co heterojunction on porous g-C3N4 nanosheets as a highly efficient catalyst for hydrogen generation.

Designing non-precious catalysts to synergistically achieve a facilitated exposure of abundant active sites is highly desired but remains a significant challenge. Herein, a hetero-structured catalyst CoP-Co supported on porous g-C3N4 nanosheets (CoP-Co/CN-I) was prepared by pyrolysis and P-inducing strategy. The optimal catalyst achieves a turnover frequency (TOF) of 26 min-1 at room temperature and the apparent activation energy (Ea) is 35.5 kJ·mol-1. The catalytic activity is ranked top among the non-precious metal phosphides or the other supports. Meanwhile, the catalytic activity has no significant decrease even after 5 cycles. The CoP/Co interfaces provide richly exposed active sites, optimize hydrogen/water absorption free energy via electronic coupling, and thus improve the catalytic activity. The experimental results reveal that the CoP/Co heterojunction improves the catalytic activity due to the construction of dual-active sites. This research facilitates the innovative construction of non-noble metal catalysts to meet industrial demand for heterogeneous catalysis.

Precise Design and Modification Engineering of Single-Atom Catalytic Materials for Oxygen Reduction.

Due to their unique electronic and structural properties, single-atom catalytic materials (SACMs) hold great promise for the oxygen reduction reaction (ORR). Coordinating environmental and engineering strategies is the key to improving the ORR performance of SACMs. This review summarizes the latest research progress and breakthroughs of SACMs in the field of ORR catalysis. First, the research progress on the catalytic mechanism of SACMs acting on ORR is reviewed, including the latest research results on the origin of SACMs activity and the analysis of pre-adsorption mechanism. The study of the pre-adsorption mechanism is an important breakthrough direction to explore the origin of the high activity of SACMs and the practical and theoretical understanding of the catalytic process. Precise coordination environment modification, including in-plane, axial, and adjacent site modifications, can enhance the intrinsic catalytic activity of SACMs and promote the ORR process. Additionally, several engineering strategies are discussed, including multiple SACMs, high loading, and atomic site confinement. Multiple SACMs synergistically enhance catalytic activity and selectivity, while high loading can provide more active sites for catalytic reactions. Overall, this review provides important insights into the design of advanced catalysts for ORR.

Co-Adjusting d-Band Center of Fe to Accelerate Proton Coupling for Efficient Oxygen Electrocatalysis.

The problem in d-band center modulation of transition metal-based catalysts for the rate-determining steps of oxygen conversion is an obstacle to boost the electrocatalytic activity by accelerating proton coupling. Herein, the Co doping to FeP is adopted to modify the d-band center of Fe. Optimized Fe sites accelerate the proton coupling of oxygen reduction reaction (ORR) on N-doped wood-derived carbon through promoting water dissociation. In situ generated Fe sites optimize the adsorption of oxygen-related intermediates of oxygen evolution reaction (OER) on CoFeP NPs. Superior catalytic activity toward ORR (half-wave potential of 0.88 V) and OER (overpotential of 300 mV at 10 mA cm-2 ) express an unprecedented level in carbon-based transition metal-phosphide catalysts. The liquid zinc-air battery presents an outstanding cycling stability of 800 h (2400 cycles). This research offers a newfangled perception on designing highly efficient carbon-based bifunctional catalysts for ORR and OER.

Heterogeneous Catalysis in Production and Utilization of Formic Acid for Renewable Energy.

As the cleanest energy source, hydrogen has been followed with interest by researchers around the world. However, due to the internal low density of hydrogen, it cannot be stored and used efficiently which limits the hydrogen application on a huge scale. Chemical hydrogen storage is considered as a useful method for efficient handling and storage. Due to its excellent safety, formic acid stands out. It is worth noting that the matter and energy conversion is established based on formic acid, which is not referred to in the previous documentation. In this review, the latest development of research on heterogeneous catalysis via production and application of formic acid for energy application is reported. The matter and energy conversion based on formic acid are both discussed systematically. More importantly, with formic acid as the node, biomass energy shows potential to be in a dominant position in the energy conversion process. In addition, the catalytic mechanism is also mentioned. This review can provide the current state in this field and the new inspirations for developing superior catalytic systems.

Chemical Composition of Thyme (Thymus vulgaris) Extracts, Potential Inhibition of SARS-CoV-2 Spike Protein-ACE2 Binding and ACE2 Activity, and Radical Scavenging Capacity.

Water and ethanol extracts of dried thyme (Thymus vulgaris) were analyzed for chemical composition, inhibition of the SARS-CoV-2 spike protein-ACE2 interaction, inhibition of ACE2 activity, and free radical scavenging capacity. Thirty-two compounds were identified in water extract (WE) and 27 were identified in ethanol extract (EE) of thyme through HPLC-MS. The WE (33.3 mg/mL) and EE (3.3 mg/mL) of thyme inhibited the spike protein-ACE2 interaction by 82.6 and 86.4%, respectively. The thyme WE at 5 mg/mL inhibited ACE2 activity by 99%, and the EE at 5 mg/mL inhibited ACE2 by 65.8%. Total phenolics were determined to be 38.9 and 8.8 mg of GAE/g in WE and EE, respectively. The HO• scavenging capacities were 1121.1 and 284.4 µmol of TE/g in WE and EE, respectively. The relative DPPH• scavenging capacities were 126.3 µmol TE/g in WE and 28.2 µmol TE/g in EE. The ABTS•+ scavenging capacities were 267.1 µmol TE/g in WE and 96.7 µmol TE/g in EE. The results suggested that the thyme extract could be potentially used to prevent SARS-CoV-2 infection and mitigate the complications from the infection.

Chemical Composition of Rosemary (Rosmarinus officinalis L.) Extract and Its Inhibitory Effects on SARS-CoV-2 Spike Protein-ACE2 Interaction and ACE2 Activity and Free Radical Scavenging Capacities.

This study evaluated the chemical composition of rosemary water extract (RWE) and its influence on mechanisms by which the SARS-CoV-2 virus enters into cells as a potential route for reducing the risk of COVID-19 disease. Compounds in RWE were identified using UHPLC-MS/MS. The inhibitory effect of RWE was then evaluated on binding between the SARS-CoV-2 spike protein (S-protein) and ACE2 and separately on ACE2 activity/availability. Additionally, total phenolic content (TPC) and free radical scavenging capacities of RWE against HO•, ABTS•+, and DPPH• were assessed. Twenty-one compounds were tentatively identified in RWE, of which tuberonic acid hexoside was identified for the first time in rosemary. RWE dose of 33.3 mg of rosemary equivalents (RE)/mL suppressed the interaction between S-protein and ACE2 by 72.9%, while rosmarinic and caffeic acids at 3.3 µmol/mL suppressed the interaction by 36 and 55%, respectively. RWE at 5.0, 2.5, and 0.5 mg of RE/mL inhibited ACE2 activity by 99.5, 94.5, and 68.6%, respectively, while rosmarinic acid at 0.05 and 0.01 µmol/mL reduced ACE2 activity by 31 and 8%, respectively. RWE had a TPC value of 72.5 mg GAE/g. The results provide a mechanistic basis on which rosemary may reduce the risk of SARS-CoV-2 infection and the development of COVID-19.

Effects of Blanching, Freezing and Canning on the Carbohydrates in Sweet Corn.

Sweet corn is frequently consumed in the US and contains carbohydrates as major macronutrients. This study examined the effects of blanching, freezing, and canning on carbohydrates in sweet corn. Fresh bi-color sweet corn was picked in the field and processed immediately into frozen and canned samples. Simple sugars, starch, and dietary fiber (DF) (including total DF (TDF), insoluble DF (IDF) and two fractions of soluble DF (SDF)) were measured according to the AOAC methods. Additional glycomic analysis including oligosaccharides, monosaccharide composition of total polysaccharides (MCTP) and glycosidic linkage of total polysaccharides (GLTP) were analyzed using UHPLC-MS. Sucrose is the major simple sugar, and IDF is the main contributor to TDF. Sucrose and total simple sugar concentrations were not altered after blanching or freezing but were significantly reduced in canned samples. Kestose was the only oligosaccharide identified in sweet corn and decreased in all heat-treated or frozen samples. Starch content decreased in frozen samples but increased in canned samples. While two SDF fractions did not differ across all samples, blanching, freezing and canning resulted in increases in TDF and IDF. Six monosaccharides were identified as major building blocks of the total polysaccharides from MCTP analysis. Glucose and total monosaccharide concentrations increased in two canned samples. GLTP was also profoundly altered by different food processing methods. This study provided insights into the changes in the content and quality of carbohydrates in sweet corn after food processing. The data are important for accurate assessment of the carbohydrate intake from different sweet corn products.

Function of TRP channels in monocytes/macrophages.

The transient receptor potential channel (TRP channel) family is a kind of non- specific cation channel widely distributed in various tissues and organs of the human body, including the respiratory system, cardiovascular system, immune system, etc. It has been reported that various TRP channels are expressed in mammalian macrophages. TRP channels may be involved in various signaling pathways in the development of various systemic diseases through changes in intracellular concentrations of cations such as calcium and magnesium. These TRP channels may also intermingle with macrophage activation signals to jointly regulate the occurrence and development of diseases. Here, we summarize recent findings on the expression and function of TRP channels in macrophages and discuss their role as modulators of macrophage activation and function. As research on TRP channels in health and disease progresses, it is anticipated that positive or negative modulators of TRP channels for treating specific diseases may be promising therapeutic options for the prevention and/or treatment of disease.

Bimetallic Nanoalloy Catalysts for Green Energy Production: Advances in Synthesis Routes and Characterization Techniques.

Bimetallic Nanoalloy catalysts have diverse uses in clean energy, sensing, catalysis, biomedicine, and energy storage, with some supported and unsupported catalysts. Conventional synthetic methods for producing bimetallic alloy nanoparticles often produce unalloyed and bulky particles that do not exhibit desired characteristics. Alloys, when prepared with advanced nanoscale methods, give higher surface area, activity, and selectivity than individual metals due to changes in their electronic properties and reduced size. This review demonstrates the synthesis methods and principles to produce and characterize highly dispersed, well-alloyed bimetallic nanoalloy particles in relatively simple, effective, and generalized approaches and the overall existence of conventional synthetic methods with modifications to prepare bimetallic alloy catalysts. The basic concepts and mechanistic understanding are represented with purposely selected examples. Herein, the enthralling properties with widespread applications of nanoalloy catalysts in heterogeneous catalysis are also presented, especially for Hydrogen Evolution Reaction (HER), Oxidation Reduction Reaction (ORR), Oxygen Evolution Reaction (OER), and alcohol oxidation with a particular focus on Pt and Pd-based bimetallic nanoalloys and their numerous fields of applications. The high entropy alloy is described as a complicated subject with an emphasis on laser-based green synthesis of nanoparticles and, in conclusion, the forecasts and contemporary challenges for the controlled synthesis of nanoalloys are addressed.

Chemical Composition of Honeysuckle (Lonicerae japonicae) Extracts and Their Potential in Inhibiting the SARS-CoV-2 Spike Protein and ACE2 Binding, Suppressing ACE2, and Scavenging Radicals.

Honeysuckle (Lonicerae japonicae) has been used in functional tea products. The chemical compositions of the water and ethanol extracts of honeysuckle were examined in the present study, along with their potential in inhibiting SARS-CoV-2 spike protein binding to ACE2, suppressing ACE2 activity, and scavenging reactive free radicals. Thirty-six compounds were tentatively identified from the honeysuckle extracts using HPLC-MS/MS, with ten reported for the first time in honeysuckle. Both honeysuckle extracts inhibited the binding of SARS-CoV-2 spike protein to ACE2, as well as ACE2 activity. The ethanol extract exhibited a 100% inhibition on binding of the SARS-CoV-2 spike protein to ACE2 at 100 mg botanical equivalent/mL, whereas the water extract had a 65% binding inhibition at the same concentration. Furthermore, the water extract exhibited 90% ACE2 activity inhibition, which was stronger than that of the ethanol extract (62% inhibition) at the same botanical weight concentration. In addition, higher total phenolic contents and greater scavenging activities against hydroxyl (HO•), DPPH•, and ABTS•+ radicals were observed in the water extract than the ethanol extract counterpart on a dry botanical weight concentration basis. These findings suggest honeysuckle has the potential to reduce the risk of SARS-CoV-2 infection and the development of severe COVID-19 symptoms.

Bioactive Compositions of Cinnamon (Cinnamomum verum J. Presl) Extracts and Their Capacities in Suppressing SARS-CoV-2 Spike Protein Binding to ACE2, Inhibiting ACE2, and Scavenging Free Radicals.

Cinnamon (Cinnamomum verum J. Presl) bark and its extracts are popular ingredients added to food and supplement products. It has various health effects, including potentially reducing the risk of coronavirus disease-2019 (COVID-19). In our study, the bioactives in cinnamon water and ethanol extracts were chemically identified, and their potential in suppressing SARS-CoV-2 spike protein-angiotensin-converting enzyme 2 (ACE2) binding, reducing ACE2 availability, and scavenging free radicals was investigated. Twenty-seven and twenty-three compounds were tentatively identified in cinnamon water and ethanol extracts, respectively. Seven compounds, including saccharumoside C, two emodin-glucuronide isomers, two physcion-glucuronide isomers, and two type-A proanthocyanidin hexamers, were first reported in cinnamon. Cinnamon water and ethanol extracts suppressed the binding of SARS-CoV-2 spike protein to ACE2 and inhibited ACE2 activity in a dose-dependent manner. Cinnamon ethanol extract had total phenolic content of 36.67 mg gallic acid equivalents (GAE)/g and free radical scavenging activities against HO• and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS•+) of 1688.85 and 882.88 µmol Trolox equivalents (TE)/g, which were significantly higher than those of the water extract at 24.12 mg GAE/g and 583.12 and 210.36 µmol TE/g. The free radical scavenging activity against 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•) of cinnamon ethanol extract was lower than that of the water extract. The present study provides new evidence that cinnamon reduces the risk of SARS-CoV-2 infection and COVID-19 development.

The role of ion channels in immune-related diseases.

Ion channel is an integral membrane protein that allows the permeation of charge ions across hydrophobic phospholipid membranes, including plasma membranes and organelle membranes (such as mitochondria, endoplasmic reticulum and vacuoles), which are widely distributed in various cells and tissues, such as cardiomyocytes, smooth muscle cells, and nerve cells. Ion channels establish membrane potential by regulating ion concentration and membrane potential. Membrane potential plays an important role in cells. Studies have shown that ion channels play a role in a number of immune-related diseases caused by functional defects in ion channels on immune or non-immune cells in major human organs, usually affecting specific organs or multiple organs. The present review discusses the relationship between ion channels and immune diseases in major organs of the human body.

The role of Nod-like receptor protein 3 inflammasome activated by ion channels in multiple diseases.

The inflammasome is a multimeric protein complex located in the cytoplasm that is activated by many factors and subsequently promotes the release of proinflammatory factors such as interleukin (IL)-1ß and IL-18, resulting in a series of inflammatory responses that ultimately lead to the occurrence of various diseases. The Nod-like receptor protein 3 (NLRP3) inflammasome is the most characteristic type and the most widely studied among many inflammasomes. Activation of the NLRP3 inflammasome is closely related to the occurrence of many diseases, such as Alzheimer's disease. At present, a large number of studies have focused on the mechanisms underlying the activation of the NLRP3 inflammasome. Plenty of articles have reported the activation of the NLRP3 inflammasome by various ions, such as K+ and Na+ reflux and Ca2+ influx. However, few articles have reviewed the effects of various ion channels on the activation of the NLRP3 inflammasome and the relationship between the diseases caused by these proteins. This article mainly summarizes the relationship between intracellular and extracellular ion activities and ion channels and the activation of the NLRP3 inflammasome. We also provide a general summary of the diseases of each system caused by NLRP3 activation. We hope that more research will provide options for the treatment of diseases driven by the NLRP3 inflammasome.

Transbronchial needle aspiration combined with cryobiopsy in the diagnosis of mediastinal diseases: a multicentre, open-label, randomised trial.

BACKGROUND: Transbronchial mediastinal cryobiopsy is a novel sampling technique for mediastinal disease. Despite the possibility of lung cancer misdiagnosis, the improved diagnostic yield of this approach for non-lung-cancer lesions compared with standard endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) highlights its diagnostic potential as a complementary technique to conventional biopsy. We aimed to evaluate the safety profile and added value of the combined use of transbronchial mediastinal cryobiopsy and standard EBUS-TBNA for the diagnosis of mediastinal diseases. METHODS: We conducted an open-label, randomised trial at three hospital sites in Europe and Asia. Eligible patients were aged 15 years or older, with at least one mediastinal lesion of 1 cm or longer in the short axis that required diagnostic bronchoscopy. Participants were randomly assigned (1:1) using a block randomisation scheme generated by a computer (block size of four participants based on a random table from an independent statistician) to the combined use of EBUS-TBNA and transbronchial mediastinal cryobiopsy (combined group) or EBUS-TBNA alone (control group). Because of the nature of the intervention, neither participants nor investigators were masked to group assignment. The coprimary outcomes were differences in procedure-related complications and diagnostic yield (defined as the proportion of participants for whom mediastinal biopsy led to a definitive diagnosis), assessed in the full analysis set, including all the patients who met the eligibility criteria and had a biopsy. A fully paired, intraindividual diagnostic analysis in participants who had both needle aspiration and mediastinal cryobiopsy was conducted, in addition to interindividual comparisons. This trial is now complete and is registered with ClinicalTrials.gov, NCT04572984. FINDINGS: Between Oct 12, 2020, and Sept 9, 2021, 297 consecutive patients were assessed for eligibility and 271 were enrolled and randomly assigned to the combined group (n=136) or the control group (n=135). The addition of cryobiopsy to standard sampling significantly increased the overall diagnostic yield for mediastinal lesions, as shown by both interindividual (126 [93%] of 136 participants in the combined group vs 109 [81%] of 135 in the control group; risk ratio [RR] 1·15 [95% CI 1·04-1·26]; p=0·0039) and intraindividual (126 [94%] of 134 vs 110 [82%] of 134; RR 1·15 [95% CI 1·05-1·25]; p=0·0026) analyses. In subgroup analyses in the intraindividual population, diagnostic yields were similar for mediastinal metastasis (68 [99%] of 69 participants in the combined group vs 68 [99%] of 69 in the control group; RR 1·00 [95% CI 0·96-1·04]; p=1·00), whereas the combined approach was more sensitive than standard needle aspiration in benign disorders (45 [94%] of 48 vs 32 [67%] of 48; RR 1·41 [95% CI 1·14-1·74]; p=0·0009). The combined approach also resulted in an improved suitability of tissue samples for molecular and immunological analyses of non-small-cell lung cancer. The incidence of adverse events related to the biopsy procedure did not differ between trial groups, as grade 3-4 airway bleeding occurred in three (2%) patients in the combined group and two (1%) in the control group (RR 0·67 [95% CI 0·11-3·96]; p=1·00). There were no severe complications causing death or disability. INTERPRETATION: The addition of mediastinal cryobiopsy to standard EBUS-TBNA resulted in a significant improvement in diagnostic yield for mediastinal lesions, with a good safety profile. These data suggest that this combined approach is a valid first-line diagnostic tool for mediastinal diseases. FUNDING: National Natural Science Foundation of China.