Diagnostic outcomes of radial endobronchial ultrasound bronchoscopy guided by manual navigation in the evaluation of peripheral pulmonary lesions: An observational study.

BACKGROUND AND AIMS: Manual navigation (MN), drawing a bronchoscopic road map simply by looking at the consecutive computed tomography (CT), is feasible and economical. However, scant data about the use of MN in radial endobronchial ultrasound (r-EBUS) bronchoscopy have been documented till now. We aimed to evaluate the diagnostic performance of r-EBUS bronchoscopy guided by MN for diagnosing peripheral pulmonary lesions (PPLs) and to determine clinical factors affecting the diagnostic yield. METHODS: We performed a retrospective, cohort study of consecutive patients with PPLs who underwent r-EBUS bronchoscopic biopsy via guidance of MN from May 2020 to June 2021 in our Respiratory Endoscopic Division. The overall diagnostic yield of MN-guided r-EBUS, the factors affecting the yield, and the diagnostic performance for malignancy were evaluated. RESULTS: A total of 102 patients (103 lesions) were evaluated. The overall diagnostic yield of MN-guided r-EBUS was 82.0%, and it ranged from 79.6% to 82.5%, assuming the undermined cases were all positive cases (79.6%) or negatives (82.5%). The sensitivity of MN-guided r-EBUS for malignancy was 71.4%, ranging from 68.2% to 71.4%, the specificity was 100%, the positive predictive value was 100%, and the negative predictive value was 67.3%, ranging from 63.8% to 69.0%. The multivariate logistic regression showed that "bronchus sign on CT" was the only predictor of the overall diagnostic yield (odds ratio = 11.5, 95% confidence interval: 1.9-70.9, P = 0.009). CONCLUSIONS: MN-guided r-EBUS is feasible in diagnosing PPLs, especially for lesions with bronchus sign on CT.

Surgical excision and radiotherapy for brain metastasis from colorectal cancer: How frailty and comorbidity indices influence outcome.

The incidence of brain metastasis (BM) from colorectal cancer (CRC) is increasing. This study aims to identify the clinical prognosticators and evaluate the prognostic validity of common comorbidity indices in patients with BM from CRC. This retrospective single-center study analyzed 93 patients with BM from CRC who received surgical excision and/or radiotherapy. The clinical characteristics and prognostic indices including the 5-item modified frailty index (mFI-5) and prognostic nutritional index (PNI) were calculated from the collected patient data and analyzed. In this study, 66 (71.0%), 10 (10.8%), and 17 (18.3%) patients received whole-brain radiotherapy (WBRT) alone, surgery alone, and surgery plus WBRT, respectively. The median survival of all patients was 3.98 months (IQR: 1.74-7.99). The 2- and 3-year survival rates were 7.4% and 3.7%, respectively. Controlled primary tumor (p = 0.048), solitary BM (p = 0.001), surgery + radiation (p < 0.001), and greater PNI (p = 0.001) were independent predictors of favorable survival. In surgically treated patients, uncontrolled primary tumor (p = 0.006), presence of multiple BM (p < 0.001), and MFI-5 ≥ 2 (p = 0.038) were independent prognosticators. For patients who received WBRT, the presence of two (p = 0.004) or multiple (p < 0.001) BM and PNI (p < 0.001) were independent survival predictors MFI-5, multiple BM, and the status of the primary tumor were independent prognosticators for patients who underwent surgery for CRCBM. For patients who received WBRT, the PNI and the number of BM were independent survival predictors.

Simple coiling of middle meningeal artery embolization for chronic subdural hematoma: An inverse probability of treatment weighting matched cohort study.

BACKGROUND: Middle meningeal artery embolization (MMAE) for chronic subdural hematoma (CSDH) has gained much attention in recent years. However, unintended embolization may occur when employing liquid embolic agents or particles. We present our clinical experience in simple coiling of MMAE to manage CSDH. METHODS: Patients underwent either surgical evacuation or MMAE with simple coiling for CSDH were reviewed. Clinical and radiographic outcomes were assessed at admission, 1-month, and 6-month intervals. Two treatment groups were matched with inverse probability of treatment weighting. RESULTS: One hundred twelve patients were included, with 27 patients in MMAE group and 87 patients in surgery group. In MMAE group, significant reductions were observed in hematoma width (admission vs. 1-month, 2.04 [1.44-2.60] cm vs. 0.62 [0.37-0.95] cm, p < 0.001). The adjusted odds ratio (aOR) of surgical rescue rate (0.77 95%CI 0.13-4.47, p = 0.77), hematoma reduction (>50%) (0.21 95%CI 0.04-1.07, p = 0.06), and midline shift improvement rate (3.22, 95%CI 0.84-12.4, p = 0.09) had no substantial disparities between two groups at 1-month follow-up. In addition, no significant difference was noted between two groups in terms of hematoma reduction (>50%) at 6-month follow-up (aOR 1.09 95%CI 0.32-3.70, p = 0.89). No procedure-related complications were found in MMA embolization group. CONCLUSION: Simple coiling for MMA had comparable outcomes with surgical evacuation for CSDH. Our findings suggest that simple coiling can be an alternative choice for liquid agents or particles in MMA embolization for CSDH with acceptable safety.

Inhibition of Bcl-6 Expression Ameliorates Asthmatic Characteristics in Mice.

OBJECTIVE: The function of Bcl-6 in T follicular helper (Tfh) cell maturation is indispensable, and Tfh cells play a pivotal role in asthma. This study investigated the impact of Bcl-6 on asthmatic traits. METHODS: The microscopic pathological alterations, airway resistance (AR), and lung compliance (LC) were determined in asthmatic mice and Bcl-6 interference mice. The surface molecular markers of Tfh cells and the Bcl-6 mRNA and protein expression were determined by flow cytometry, RT-qPCR, and Western blotting, respectively. The relationships between the Tfh cell ratio and the IgE and IgG1 concentrations in peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage fluid (BALF) were determined. RESULTS: Asthmatic inflammatory changes were observed in the lung tissue and were attenuated by Bcl-6 siRNA and dexamethasone (DXM). Asthmatic mice exhibited an increased AR and a decreased LC, while Bcl-6 siRNA or DXM mitigated these changes. The percentages of Tfh cells and eosinophils were significantly increased in the asthmatic mice, and they significantly decreased after Bcl-6 inhibition or DXM treatment. RT-qPCR and Western blotting analyses revealed that the Bcl-6 expression level in PBMCs was significantly higher in asthmatic mice, and it decreased following Bcl-6 inhibition or DXM treatment. The IgE expression in the serum and BALF and the B cell expression in PBMCs exhibited a similar trend. In asthmatic mice, the ratio of Tfh cells in the peripheral blood showed a strong positive correlation with the IgE levels in the serum and BALF, but not with the IgG1 levels. CONCLUSION: The amelioration of airway inflammation and airway hyper-responsiveness is achieved through Bcl-6 suppression, which effectively hinders Tfh cell differentiation, ultimately resulting in a concurrent reduction in IgE production.

Decompressive Craniectomy versus Craniotomy for Acute Subdural Hematoma: Updated meta-analysis of real-world clinical outcome after RESCUE-ASDH trial.

INTRODUCTION: The RESCUE-ASDH trial found that disability and quality-of-life outcomes were similar between craniotomy and decompressive craniectomy for traumatic acute subdural hematoma, contrasting previous literature. This meta-analysis aims to validate the applicability of RESCUE-ASDH results using real-world data in acute subdural hematoma patients. METHODS: We searched Chocrane, Embase, and MEDLINE for relevant articles reporting clinical outcomes of craniotomy and decompressive craniectomy. Meta-analysis utilized R software with the restricted maximum likelihood method for random-effects meta-analyses, presenting odds ratios and 95% confidence intervals with Hartung-Knapp-Sidik-Jonkman adjustment for heterogeneity. RESULTS: Besides RESCUE-ASDH, 5 retrospective studies were included, spanning 2006-2016. A total of 961 patients with traumatic ASDH were included in this study (Craniotomy = 467; Decompressive craniotomy = 494). The pooled analysis of retrospective studies showed no significant difference in poor clinical outcomes between the two groups (OR 0.59, 95% CI, 0.32 to 1.10). These findings align with the RESCUE-ASDH trial (OR 0.84, 95% CI, 0.58 to 1.23). Mortality rate was significant higher in patients undergoing craniectomy in pooled result of retrospective studies (OR 0.59, 95% CI, 0.32 to 1.10). In RESCUE-ASDH trial, reoperation rate was higher in the craniotomy group, but the pooled result of retrospective did not show significant difference between the craniotomy and craniectomy group. CONCLUSIONS: This real-world evidence confirms the RESCUE-ASDH trial results. Both craniotomy and decompressive craniectomy yielded similar disability and quality-of-life outcomes for traumatic acute subdural hematoma patients. LEVEL OF EVIDENCE: Level 2, Systematic and meta-analysis.

Systematic Review and Meta-analysis of Radial or Femoral Access for Carotid Stenting.

PURPOSE: There is a growing interest in performing coronary artery and neurovascular interventions via the radial artery; however, few studies have examined the outcomes of transradial carotid stenting. Therefore, our study aimed to compare cerebrovascular outcomes and crossover rates in carotid stenting between transradial and traditional transfemoral approaches. METHODS: A systematic review was performed by searching three electronic databases from inception to June 2022 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. In addition, random effect meta-analysis was used to pool the odds ratios (ORs) for stroke, transient ischemic attack, major adverse cardiac events, death, major vascular access site complications, and procedure crossover rates between the transradial and transfemoral approaches. RESULTS: A total of 6 studies were included involving a total of n = 567 transradial and n = 6176 transfemoral procedures. The ORs for stroke, transient ischemic attack, and major adverse cardiac events were 1.43 (95% confidence interval, CI 0.72-2.86, I2 = 0), 0.51 (95% CI 0.17-1.54, I2 = 0), and 1.08 (95% CI 0.62-1.86, I2 = 0), respectively. Neither the major vascular access site complication rate (OR 1.11, 95% CI 0.32-3.87, I2 = 0) nor crossover rate (OR 3.94, 95% CI 0.62-25.11, I2 = 57%) showed statistically significant differences between the two approaches. CONCLUSION: The modest quality of the data suggested comparable procedural outcomes between the transradial and transfemoral approaches when performing carotid stenting; however, high level evidence regarding postoperative brain images and risk of stroke in transradial carotid stenting are lacking. Therefore, it is reasonable for interventionists to weigh up the risks of neurological events and potential benefits, including fewer access site complications, before choosing the radial or femoral arteries as access sites. Future large-scale randomized controlled trials are imperative.

Outcomes of surgery and subsequent therapy for central nervous system oligoprogression in EGFR-mutated NSCLC patients.

BACKGROUND: Oligoprogression is an emerging issue in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). However, the surgical treatment for central nervous system (CNS) oligoprogression is not widely discussed. We investigated the outcomes of craniotomy with adjuvant whole-brain radiotherapy (WBRT) and subsequent therapies for CNS oligoprogression in patients with EGFR-mutated NSCLC. METHODS: NSCLC patients with CNS oligoprogression were identified from a tertiary medical center. The outcomes of surgery with adjuvant WBRT or WBRT alone were analyzed, along with other variables. Overall survival and progression-free survival were analyzed using the log-rank test as the primary and secondary endpoints. A COX regression model was used to identify the possible prognostic factors. RESULTS: Thirty-seven patients with CNS oligoprogression who underwent surgery or WBRT were included in the study after reviewing 728 patients. Twenty-one patients underwent surgery with adjuvant WBRT, and 16 received WBRT alone. The median overall survival for surgery and WBRT alone groups was 43 (95% CI 17-69) and 22 (95% CI 15-29) months, respectively. Female sex was a positive prognostic factor for overall survival (OR 0.19, 95% CI 0.06-0.57). Patients who continued previous tyrosine kinase inhibitors (OR 3.48, 95% CI 1.06-11.4) and induced oligoprogression (OR 3.35, 95% CI 1.18-9.52) were associated with worse overall survival. Smoking history (OR 4.27, 95% CI 1.54-11.8) and induced oligoprogression (OR 5.53, 95% CI 2.1-14.7) were associated with worse progression-free survival. CONCLUSIONS: Surgery combined with adjuvant WBRT is a feasible treatment modality for CNS oligoprogression in patients with EGFR-mutated NSCLC. Changing the systemic-targeted therapy after local treatments may be associated with improved overall survival.

Endovascular treatment in bilateral cavernous sinus dural arteriovenous fistulas: a systematic review and meta-analysis.

Few studies have discussed the disease nature and treatment outcomes for bilateral cavernous sinus dural arteriovenous fistula (CSDAVF). This study aimed to investigate the clinical features and treatment outcomes of bilateral CSDAVF. Embase, Medline, and Cochrane library were searched for studies that specified the outcomes of bilateral CSDAVF from inception to April 2022. The classification, clinical presentation, angiographic feature, surgical approach, and treatment outcomes were collected. Meta-analysis was performed using the random effects model. Eight studies reporting 97 patients were included. The clinical presentation was mainly orbital (n = 80), cavernous (n = 52) and cerebral (n = 5) symptoms. The most approached surgical route was inferior petrosal sinus (n = 80), followed by superior orbital vein (n = 10), and alternative approach (n = 7). Clinical symptoms of 88% of the patients (95% CI 80-93%, I2 = 0%) were cured, and 82% (95% CI 70-90%, I2 = 7%) had angiographic complete obliteration of fistulas during follow up. The overall complication rate was 18% (95% CI 11-27%, I2 = 0%). Therefore, endovascular treatment is an effective treatment for bilateral CSDAVF regarding clinical or angiographic outcomes. However, detailed evaluation of preoperative images and comprehensive surgical planning of the approach route are mandatory owing to complexity of the lesions.

Evaluation of the safety, radiographic and resident training results of thoracic pedicle screws placement using resection of the transverse process.

OBJECTIVE: This study aimed at the evaluation and assessment of a simple method, the transverse process resection (TPR) technique, for freehand thoracic pedicle screw placement and the learning curve for trainee surgeons. METHODS: In the TPR technique, the tip of the thoracic transverse process (TP) is removed to create an entry point in the cancellous bone of the TP, and the thoracic pedicle is cannulated from the TP. We retrospectively evaluated the safety and radiographic results of the TPR technique and compared with that of conventional pedicle screws. The training performance of seven neurosurgical residents with TPR techniques were evaluated. RESULTS: Among 46 patients, a total of 322 thoracic screws were analyzed, including 178 screws placed using the TPR technique and 144 screws using the conventional straight-forward (SF) technique. TPR screws had greater medial angulations in all levels from T2 to T12 compared to SF screws (p < 0.001). The incidence of pedicle breach was lower in the TPR screws compared to SF screws (6.2% vs. 21.5%, p < 0.001), especially for screws placed by residents (6.7% vs. 29.6%, p < 0.001). Residents had improved performance following a cadaveric training course on the TPR technique (p = 0.001). CONCLUSION: This study demonstrated the safety of the TPR technique for thoracic pedicle screw placement and its short learning curve for trainee surgeons.

Quantification of vessel separation using the carotid-jugular angle to predict the nerve origin of neck peripheral nerve sheath tumours: a pooled analysis of cases from the literature and a single-center cohort.

BACKGROUND: Postoperative nerve palsy is a major complication following resection of neck peripheral nerve sheath tumours (PNSTs). Accurate preoperative identification of the nerve origin (NO) can improve surgical outcomes and patient counselling. MATERIAL AND METHODS: This study was a retrospective cohort and quantitative analysis of the literature. The authors introduced a parameter, the carotid-jugular angle (CJA), to differentiate the NO. A literature review of neck PNST cases from 2010 to 2022 was conducted. The CJA was measured from eligible imaging data, and quantitative analysis was performed to evaluate the ability of the CJA to predict the NO. External validation was performed using a single-centre cohort from 2008 to 2021. RESULTS: In total, 17 patients from our single-centre cohort and 88 patients from the literature were analyzed. Among them, 53, 45, and 7 patients had sympathetic, vagus, and cervical nerve PNSTs, respectively. Vagus nerve tumours had the largest CJA, followed by sympathetic tumours, whereas cervical nerve tumours had the smallest CJA ( P <0.001). Multivariate logistic regression identified a larger CJA as a predictor of vagus NO ( P <0.001), and receiver operating characteristic (ROC) analysis showed an area under the curve (AUC) of 0.907 (0.831-0.951) for the CJA to predict vagus NO ( P <0.001). External validation showed an AUC of 0.928 (0.727-0.988) ( P <0.001). Compared with the AUC of the previously proposed qualitative method (AUC=0.764, 0.673-0.839), that of the CJA was greater ( P =0.011). The cut-off value identified to predict vagus NO was greater than or equal to 100°. Receiver operating characteristic analysis showed an AUC of 0.909 (0.837-0.956) for the CJA to predict cervical NO ( P <0.001), with a cut-off value less than 38.5°. CONCLUSIONS: A CJA greater than or equal to 100° predicted a vagus NO and a CJA less than 100° predicted a non-vagus NO. Moreover, a CJA less than 38.5 was associated with an increased likelihood of cervical NO.

Iodine-125 seed brachytherapy combined with pembrolizumab for advanced non-small-cell lung cancer after failure of first-line chemotherapy: A report of two cases and literature review.

Although immunotherapy regimens for advanced non-small-cell lung cancer (NSCLC) improve survival in selected sub-populations, their efficacy remains far from ideal due to underlying resistance; therefore, multimodal combination strategies are needed to optimize their efficacy. In our report, two patients with advanced NSCLC with negative targetable mutations, who had failed first-line chemotherapy were treated with combined therapy of computed tomography (CT)-guided percutaneous iodine-125 seed implantation and pembrolizumab. After combination treatment, both patients achieved partial response (PR), and sustained a long progression-free survival (PFS) without obvious therapy-related adverse reactions. Iodine-125 seeds bring no long-term adverse events and effectively amplify anti-tumor immune response induced by immunotherapy; thus, this combined therapy might be a promising alternative for NSCLC.

Transthyretin attenuates TDP-43 proteinopathy by autophagy activation via ATF4 in FTLD-TDP.

TAR DNA-binding protein-43 (TDP-43) proteinopathies are accompanied by the pathological hallmark of cytoplasmic inclusions in the neurodegenerative diseases, including frontal temporal lobar degeneration-TDP and amyotrophic lateral sclerosis. We found that transthyretin accumulates with TDP-43 cytoplasmic inclusions in frontal temporal lobar degeneration-TDP human patients and transgenic mice, in which transthyretin exhibits dramatic expression decline in elderly mice. The upregulation of transthyretin expression was demonstrated to facilitate the clearance of cytoplasmic TDP-43 inclusions through autophagy, in which transthyretin induces autophagy upregulation via ATF4. Of interest, transthyretin upregulated ATF4 expression and promoted ATF4 nuclear import, presenting physical interaction. Neuronal expression of transthyretin in frontal temporal lobar degeneration-TDP mice restored autophagy function and facilitated early soluble TDP-43 aggregates for autophagosome targeting, ameliorating neuropathology and behavioural deficits. Thus, transthyretin conducted two-way regulations by either inducing autophagy activation or escorting TDP-43 aggregates targeted autophagosomes, suggesting that transthyretin is a potential modulator therapy for neurological disorders caused by TDP-43 proteinopathy.

Short-Term Cortical Electrical Stimulation during the Acute Stage of Traumatic Brain Injury Improves Functional Recovery.

Functional restoration is an important issue in the treatment of traumatic brain injury (TBI). Various electrical stimulation devices and protocols have been applied in preclinical studies and have shown therapeutic potential for brain trauma. Short-term invasive cortical electrical stimulation during the acute stage of TBI might be a feasible adjuvant therapy for patients with moderate-to-severe brain injury receiving neurosurgical treatment in the intensive care unit. However, the therapeutic effects of short-term multisession cortical electrical stimulation for brain trauma are not clear. This study explored the therapeutic effects of acute-stage short-term cortical electrical stimulation on TBI. We conducted seven sessions of one-hour cortical electrical stimulation from day 0 to day 6 in rats after brain trauma by controlled cortical impact and then evaluated the functional outcome and histopathological changes. Our data showed that short-term cortical electrical stimulation improved motor coordination, short-term memory, and learning ability and attenuated neurological severity after brain trauma. Lesion volume, apoptosis, and gliosis after brain trauma were reduced, and trauma-induced neurogenesis in the hippocampus for the innate neural reparative response was increased. Our study demonstrated that short-term cortical electrical stimulation applied in the acute stage of traumatic brain injury is a potential adjuvant therapy to improve the recovery of neurological deficits.

Somatosensory Cortical Electrical Stimulation After Reperfusion Attenuates Ischemia/Reperfusion Injury of Rat Brain.

Objective: Ischemic stroke is an important cause of death and disability worldwide. Early reperfusion by thrombolysis or thrombectomy has improved the outcome of acute ischemic stroke. However, the therapeutic window for reperfusion therapy is narrow, and adjuvant therapy for neuroprotection is demanded. Electrical stimulation (ES) has been reported to be neuroprotective in many neurological diseases. In this study, the neuroprotective effect of early somatosensory cortical ES in the acute stage of ischemia/reperfusion injury was evaluated. Methods: In this study, the rat model of transient middle cerebral artery occlusion was used to explore the neuroprotective effect and underlying mechanisms of direct primary somatosensory (S1) cortex ES with an electric current of 20 Hz, 2 ms biphasic pulse, 100 µA for 30 min, starting at 30 min after reperfusion. Results: These results showed that S1 cortical ES after reperfusion decreased infarction volume and improved functional outcome. The number of activated microglia, astrocytes, and cleaved caspase-3 positive neurons after ischemia/reperfusion injury were reduced, demonstrating that S1 cortical ES alleviates inflammation and apoptosis. Brain-derived neurotrophic factor (BDNF) and phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway were upregulated in the penumbra area, suggesting that BDNF/TrkB signals and their downstream PI3K/Akt signaling pathway play roles in ES-related neuroprotection. Conclusion: This study demonstrates that somatosensory cortical ES soon after reperfusion can attenuate ischemia/reperfusion injury and is a promising adjuvant therapy for thrombolytic treatment after acute ischemic stroke. Advanced techniques and devices for high-definition transcranial direct current stimulation still deserve further development in this regard.

Outcome of Wingspan Stent Using Aggressive Post-stent Balloon Dilation for Intracranial Atherosclerosis Stenosis.

Background: Wingspan stent has gained interest for better long-term outcomes for intracranial atherosclerosis disease (ICAD). However, in-stent restenosis still presents as a problem and may cause postoperative neurological events. We aimed to find a way to prevent in-stent restenosis. Method: Patients with stenosis >70% ICAD were treated with wingspan stent and were retrospectively reviewed. The patients were separated into two groups: one with post-dilation and the other without post-dilation. The outcomes of wingspan stenting were compared immediately after the surgery and at a 1-year follow-up. Results: Overall, 28 patients were included for analysis, with 15 patients undergoing post-dilation and 13 patients not undergoing the procedure. The extent of stenosis was significantly lower in the post-dilation group than in the no post-dilation group, both immediately after the surgery (14.8 ± 10.2 vs. 28.5 ± 14.5%, p < 0.01) and at 1-year follow-up (25.8 ± 18.0 vs. 50.1 ± 23.2%, p < 0.01). The post-dilation method immediately expanded the stent diameter (2.89 ± 0.48 vs. 3.05 ± 0.44 mm, p < 0.001), and the diameter still increased at 1-year follow-up (3.05 ± 0.44 vs. 3.12 ± 0.43 mm, p < 0.01) due to the self-expandable property of the wingspan. Similarly, in the no post-dilation group, the stent size was also increased (2.70 ± 0.67 vs. 2.80 ± 0.64 mm, p < 0.01). However, at 1-year follow up, the luminal diameter was stationary in the post-dilation group (2.36 ± 0.73 vs. 2.46 ± 0.82 mm, p = 0.88) and decreased in the no post-dilation group (2.24 ± 0.56 vs. 1.60 ± 0.79 mm, p < 0.01). The periprocedural complication rate was similar between the groups. Conclusion: The post-dilation method can be feasibly performed and can offer better stent expansion and apposition in the wingspan system. By applying this technique, we might prevent in-stent restenosis and improve neurological outcomes.

Electroactive polymer-based inner vessel-wall pressure transducer capable of integration with a PTA balloon catheter for examining blood vessel health.

This study presents a state-of-the-art soft and biocompatible transducer capable of detecting vessel inner-wall pressure for biomedical applications. The device includes a 3D electroactive polymer core element encapsulated by polydimethylsiloxane with an ellipsoidal structure. The device produces a voltage output when its sensing mechanism experiences different pressures, resulting in deformation at different orientations. Thus, it can be employed to detect the pressure exerted by inner vessel walls of different stiffness values. The output voltage is induced by the strain experienced by the sensing mechanism of the device without the need for any external electrical power source. The core element, which is made of an ionic polymer-metal composite, possesses a unique hollow design; this allows a catheter to pass through, and the core element can be anchored at an arbitrary position on the catheter. We also demonstrate that the fabricated device can be integrated with a medically used percutaneous transluminal angioplasty balloon catheter to form a smart sensing module. This module can detect different levels of fat accumulation around the inner wall of a blood vessel phantom. Evaluating vessel blockage and stiffness using the signals acquired from the developed device is discussed.

Multivalence-Actuated DNA Nanomachines Enable Bicolor Exosomal Phenotyping and PD-L1-Guided Therapy Monitoring.

Exosome-associated liquid biopsies are hampered by challenges in the exosomal quantification and phenotyping. Here, we present a bioinspired exosome-activated DNA molecular machine (ExoADM) with multivalent cyclic amplification that enables highly sensitive detection and phenotyping of circulating exosomes. ExoADM harbors two (an exposed and a hidden) DNA toehold domains that actuate sequential branch migration and multivalent recycling in response to exosomal surface markers. Importantly, this self-powered ExoADM achieves a high sensitivity (33 particles/µL) and is compatible with another DNA nanomachine targeting different exosomal surface markers for dual-color phenotyping. Using this strategy, we can simultaneously track the dynamic changes of ExoPD-L1 and ExoCD63 expression induced by signaling molecules. Further, we found that their expression levels on circulating exosomes could well differentiate cancer patients from the normal individuals. More importantly, ExoPD-L1 levels could reflect the efficacy of different treatments and guide anti-PD-1 immunotherapy, suggesting the potential of ExoPD-L1 in clinical diagnosis and targeted therapy monitoring.

High temperature inhibits the accumulation of storage materials by inducing alternative splicing of OsbZIP58 during filling stage in rice.

High temperature (HT) has an adverse effect on rice grain filling by inhibiting the accumulation of storage materials. However, the regulatory mechanism of this inhibition remains unknown. Here, we report that Opaque2 like transcription factor OsbZIP58 is a key factor regulating storage material accumulation under HT. The OsbZIP58 gene promotes expression of many seed storage protein genes and starch synthesis genes while inhibits expression of some starch hydrolyzing α-amylase genes under HT. The loss of OsbZIP58 function leads to floury and shrunken endosperms and dramatically reduced storage materials in the seeds under HT. HT is found to affect alternative splicing of OsbZIP58, promoting the formation of the truncated OsbZIP58ß protein form over the full-length OsbZIP58α protein form. The OsbZIP58ß form has a lower transcriptional activity than the OsbZIP58α form, especially under HT condition. Interestingly, rice varieties with less heat sensitivity have reduced alternative splicing of OsbZIP58. Therefore, OsbZIP58 is a crucial gene in regulating storage material accumulation under HT and lower alternative splicing of OsbZIP58 may contribute to heat tolerance during grain filling.

The qSAC3 locus from indica rice effectively increases amylose content under a variety of conditions.

BACKGROUND: Amylose content (AC) is a critical factor for the quality of rice. It is determined by the biosynthesis gene Waxy (Wx) and a variety of quantitative trait loci (QTLs). Although many QTLs have been reported to affect rice AC, few of them have been investigated under varying growth conditions, especially various temperatures, which are known to greatly influence the AC. RESULTS: We analyzed the AC at different temperatures and planting seasons in a set of chromosome segment substitution lines (CSSLs) which were derived from a cross between the indica variety 9311 and the japonica variety Nipponbare carrying the same Wxb allele. A joint analysis detected a single locus, qSAC3, with a high logarithm of odds (LOD) score in four different conditions. The qSAC3 from indica 9311 (qSAC3ind) substantially increased the AC in japonica Nipponbare under all tested growth conditions. Furthermore, introducing the qSAC3ind into the soft rice variety Nangeng9108 with Wxmq, a mutant allele of Wxb, also moderately increased its AC and improved its appearance quality significantly by reducing the chalkiness of the polished rice. CONCLUSIONS: Our results indicate that the qSAC3ind could increase the AC of japonica rice in different environments as well as in the background of different Wx alleles and that qSAC3 is a valuable locus for fine-tuning the rice AC and ameliorating the dull endosperm in rice varieties with the Wxmq allele.

Significant effects of late evening snack on liver functions in patients with liver cirrhosis: A meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: Reducing post-absorptive (fasting) phase by eating late evening snacks (LESs) is a potential intervention to improve substrate utilization and reverse sarcopenia. This study analyzed the results of published randomized controlled trials and controlled clinical trials to evaluate the effects of LES on liver function of patients with cirrhosis. METHODS: A meta-analysis was conducted. The search strategy included electronic database searches, and 300 articles were searched. Eight of these articles provided qualified data for pooling and analysis. Outcomes assessments included serum albumin, total bilirubin, alanine aminotransferase, prothrombin time, and aspartate aminotransferase, complications of cirrhosis, severity of liver disease, and blood glucose levels. RESULTS: Our analysis included eight studies comprising 341 patients (167 in LES groups and 174 in control groups). The results showed that LES intervention helped to maintain liver reserves. These eight studies demonstrated that LES intervention had significant effects for liver biochemical parameters on albumin, ammonia, and prothrombin time, with respective effect sizes of 0.233, -0.425, and -0.589; liver enzymes include aspartate aminotransferase and alanine aminotransferase, with respective effect sizes of -0.320 and -0.284. Studies on clinical signs of liver dysfunction showed lower occurrence rates of ascites and hepatic encephalopathy than in the control group. LES had no significant effect on Child-Pugh score. CONCLUSIONS: The overall results of the meta-analysis indicated that having LES can improve liver function reserve for patients with liver cirrhosis, with or without hepatocellular carcinoma. LES is a promising intervention for reversing anabolic resistance and the sarcopenia of cirrhosis, resulting in an improved quality of life for patients with cirrhosis.