Gut microbiome has been increasingly recognized for its influence on a diverse array of human diseases including cancer, and may also influence the outcome of cancer therapies. A prime example is seen in immunotherapy, for which gut microbes determine the therapeutic responses associated with immune checkpoint inhibitors (ICIs) in preclinical models and patient cohorts. This evidence hints that inter-individual variations in the gut microbiota may account for the significant heterogeneity in immunotherapeutic responses to ICIs. Understanding the functional role of gut microbiome in regulating not only mucosal but also systemic immunity and cancer is critical to move forward in this era of precision medicine. What’s more, microbiota can be modified via several different strategies that are essential for the efforts in expanding immunotherapy efficacy. This review summarizes latest knowledge about the interactions between microbiome, host immunity and cancer, and strategies to modulate the microbiome with implications to be translated into clinic. FUNDING This study was supported by National Key R&D Program of China (No. 2020YFA0509200/2020YFA0509203), RGC Theme-based Res Scheme Hong Kong (T21-705/20-N).

To investigate the neuronal elements involved in the activation of corticospinal neurons in the primary motor cortex (M1).

We studied 10 healthy subjects. Cortical evoked potentials with different components induced by monophasic transcranial magnetic stimulation (TMS) in anterior-posterior and posterior-anterior currents recorded with electroencephalography (EEG) were analyzed.

EEG signatures with P25 and N45 components recorded at the C3 electrode with posterior-anterior current were larger than those with anterior-posterior current, while the signatures with P180 and N280 components recorded at the FC1 electrode with anterior-posterior current were larger than those with posterior-anterior current. The source localization analysis revealed that the cortical evoked potential with anterior-posterior current distributed both in the M1 and premotor cortex while that with posterior-anterior current only located in the M1.

We conclude that the activation of corticospinal pyramidal neurons in the M1 is affected by various neuronal elements including the local intracortical circuits in the M1 and inputs from premotor cortex with different sensitivities to TMS in opposite current directions.

Our finding helped answer a longstanding question about how the corticospinal pathway from the M1 is functionally organized and activated.

Our finding helped answer a longstanding question about how the corticospinal pathway from the M1 is functionally organized and activated.GATA3 has been reported to be positive in clear cell papillary renal cell carcinoma and papillary renal neoplasm with reverse polarity. However, its features in high-grade RCC remain unclear. Despite the emergence of novel renal entities, FH-deficient RCC remains one of the most aggressive renal neoplasms. The diagnosis is mainly based on the loss of FH at the protein level. Previous studies have shown that inclusion-like nuclei, multiple architectural patterns, FH loss, and 2SC positivity can differentiate FH-deficient RCC from other RCC. In some FH-deficient RCC cases, FH is normally expressed and is difficult to diagnose. This study included 11 FH-deficient RCC, and GATA3 showed different expression in seven cases. However, 147 papillary renal cell carcinomas were included, and GATA3 expression was negative. A comparison of clinicopathological aspects between 11 FH-deficient RCC and 30 high-grade PRCC showed statistical significance in age, size, multiple architectural patterns, inclusion-like nuclei, and prognosis. However, PRCC exhibited similar characteristics. CK7, GATA3, and FH profiles were also statistically significant. Different chromosomal alterations were found in FH-deficient RCC, and chromosomal alterations were not different between FH-deficient RCC and PRCC. GATA3 was positive in 33 % (7/21) of collecting duct carcinomas and negative in other high-grade renal neoplasms. GATA3 is negative in PRCC, but can be positive in FH-deficient RCC and collecting duct carcinoma. GATA3 expression may indicate a worse outcome in high-grade RCC with papillary architecture. We recommend GATA3 IHC for the differential diagnosis and prognostic assessment of high-grade RCC with papillary architecture.Myocarditis is an inflammatory cardiovascular disease which contributes to dilated cardiomyopathy (DCM) and heart failure. Canagliflozin (CANA) exerts anti-inflammatory and cardioprotective effects in heart failure besides its hypoglycemic effect. However, the role of CANA in myocarditis has not been elucidated. In this work, CANA treatment markedly alleviated cardiac inflammation and improved cardiac function in experimental autoimmune myocarditis (EAM) mice induced by α-myosin-heavy chain peptides. The expressions of NLRP3 inflammasome complexes (NLRP3, ASC, and Caspase-1) and their downstream molecules (IL-1β, IL-18) were significantly downregulated by CANA, accompanied with reduced Th17 cell infiltration in hearts. Furthermore, Bax/Bcl-2 ratio, Cleaved Caspase-3 protein level and the percentage of TUNEL-positive myocardial cells, which usually indicated apoptosis, were reduced by CANA treatment. These findings suggest CANA could be a valuable medication for myocarditis treatment.In recent years it has been increasingly appreciated that blood vessels are not simply suppliers of nutrients and oxygen, but actually play an exquisite regulatory role in bone development and repair. A specialized kind of endothelium, named type H because of its high expression of CD31 and Endomucin, constitutes anatomically defined vessels in proximity of the epiphyseal growth plate. Type H endothelium regulates the proliferation and differentiation of both osteoblasts and osteoclasts through the secretion of angiocrine signals and is a hub for the bidirectional molecular crosstalk between the different cell populations of the osteogenic microenvironment. Type H vessels are a key target for current translational approaches aiming at coupling angiogenesis and osteogenesis for bone repair. Open questions remain about their presence and features in notstereotyped tissues, like engineered osteogenic grafts, and the opportunities for their clinical stimulation by pharmacological treatments.Application of droplet-based methods enables (i) faster detection, (ii) increased sensitivity, (iii) characterization of the level of heterogeneity in response to antibiotics by bacterial populations, and (iv) expanded screening of the effectiveness of antibiotic combinations. Hereby, we discuss the key steps and parameters of droplet-based experiments to investigate antimicrobial resistance. We also review recent findings accomplished with these methods and highlight their advantages and capacity to yield new insights into the problem of antimicrobial resistance.

Patients with intracranial aneurysms treated with stent-assisted coil embolization (SACE) require radiological and clinical follow-up in view of in-stent stenosis (ISS). The aim of the study was to evaluate transcranial Doppler (TCD) as an alternative to more invasive digital subtraction angiography (DSA) in monitoring patients with SACE.

Over the course of 72 months, from January 2016 to December 2021, we analyzed 49 patients treated with SACE because of internal carotid artery (ICA) aneurysms (C6 ophthalmic segment or C7 communicating segment). DSA was performed in all patients at 24-months and TCD was examined preoperatively and at 3, 6, 12, and 24-months postoperatively. The degree of stenosis found on TCD was compared with the results of DSA. Preoperative and postoperative blood flow velocities, including peak systolic blood flow velocity (Vs), end diastolic velocity (Vd), and mean velocity (Vm), were compared and the optimal cutoff velocities for detecting stenosis were calculated.

Pre-embolization middle cerebral artery (MCA) and intracranial terminal internal cerebral arteries (TICA) velocities and pulsatility index (PI) did not significantly differ between the ipsilateral and contralateral sides. The blood flow velocities, Vs, Vd, and Vm, on the operation side significantly increased after SACE (P<0.05). Over the 24-month study period, 7 of the 49 patients (14.3%) exhibited angiographic ISS. find more ISS of TCD and DSA results at 24-months were compared and found to correlate well; the Cohen’s κ coefficient was 0.851 (95% CI 0.651-1.051). The optimal cutoff velocity for detecting ISS was MCA Vs =173.5cm/s.

TCD is a potentially useful adjunct for evaluating ISS after SACE.

TCD is a potentially useful adjunct for evaluating ISS after SACE.

To examine the association between positive psychological factors and the risk of pneumonia-associated mortality in a large prospective Japanese cohort.

The Japan Collaborative Cohort Study assessed 64,231 participants (26,293 men and 37,938 women), aged 40-79years, without a history of stroke, myocardial infarction, cancer or tubercules at baseline (1988-1990). We used self-administered questionnaires about lifestyle, medical history, and mental states, including three positive psychological factors, and followed-up for mortality outcomes until the end of 2009. The Cox proportional hazard model was used to calculate the multivariable hazard ratios (HRs) with 95% confidence intervals (CIs) of pneumonia-associated mortality after adjustment for potential confounding factors, mutually positive psychological factors, and consideration for the competing risk.

Having Ikigai (in Japanese) was inversely associated with the risk of pneumonia-associated mortality in both men and women; the multivariable HRs (95% CIs) for high versus low levels were 0.68 (0.48-0.97), P trend =0.090 and 0.66 (0.43-1.00), P trend=0.146, respectively. Such inverse associations were more pronounced in working men and non-working women; the multivariable HRs (95% CIs) for high versus low levels were 0.52 (0.32-0.85), P trend =0.010 and 0.59 (0.37-0.94), P trend=0.079, respectively. Being relied upon by others and Enjoyment of life was not associated with the risk in both genders.

Having Ikigai was associated with a lower risk of pneumonia-associated mortality in both genders, especially in working men and non-working women.

Having Ikigai was associated with a lower risk of pneumonia-associated mortality in both genders, especially in working men and non-working women.Antivenom is the only safe and effective treatment to neutralize snake venom. Specific anti-venom used to treat snake bite is usually obtained from horses after hyperimmunization with crude snake venom in combination with Freund’s Adjuvant. Freund’s complete and incomplete adjuvant can cause severe local and systemic acute and chronic inflammation, its potentially severe inflammatory effects have led many researchers to seek alternative immunological adjuvants. CpG-ODN formulated in a 6-O-ascorbyl palmitate nanostructure (Coa-ASC16) was more efficient as adjuvant than CpG-ODN alone using ovalbumin (OVA) as an antigen model. Particularly, immunization of mice with OVA/CpG-ODN/Coa-ASC16 resulted in high OVA specific antibody titers and IFN-γ and IL-17 secretion compared to immunization with OVA/CpG-ODN. First of all, we estimated the effect of Coa-ASC16 nanostructure preparation on venom activity. Additionally, in order to evaluate the immune response induced by this adjuvant strategy using Crotalus durissus terrificus (C.