Synergistic Adsorption and In Situ Catalytic Conversion of SO2 by Transformed Bimetal-Phenolic Functionalized Biomass.

SO2 removal is critical to flue gas purification. However, based on performance and cost, materials under development are hardly adequate substitutes for active carbon-based materials. Here, we engineered biomass-derived nanostructured carbon nanofibers integrated with highly dispersed bimetallic Ti/CoOx nanoparticles through the thermal transition of metal-phenolic functionalized industrial leather wastes for synergistic SO2 adsorption and in situ catalytic conversion. The generation of surface-SO32- and peroxide species (O22-) by Ti/CoOx achieved catalytic conversion of adsorbed SO2 into value-added liquid H2SO4, which can be discharged from porous nanofibers. This approach can also avoid the accumulation of the adsorbed SO2, thereby achieving high desulfurization activity and a long operating life over 6000 min, preceding current state-of-the-art active carbon-based desulfurization materials. Combined with the techno-economic and carbon footprint analysis from 36 areas in China, we demonstrated an economically viable and scalable solution for real-world SO2 removal on the industrial scale.

Emerging roles of circular RNAs in thyroid cancer.

As the most common endocrine-related malignant tumor, the prevalence of thyroid cancer (TC) has soared strikingly over the past thirty years then verged to stabilization or even descension temporally. Distributed in a cell-specific manner, circular RNAs (circRNAs) is a novel class of non-coding RNAs characterized by its covalently closed loop without 5'-terminal cap and 3'-terminal poly A tail, which guarantee its distinctive evolutionary conservation and exonucleases resistance. Emerging evidence indicates that circRNA participates in the pathogenesis and carcinogenesis of several cancers including thyroid cancer. In this review, we concentrated on the connection between circRNAs and thyroid cancer so as to obtain a more profound understanding. We aim to discuss this relationship between TC and circRNAs by summarizing the effect of various circRNAs on tumor biological behaviors and clinical application, and systematically outlook the conceivable application of circRNAs in TC diagnosis and therapy.

Safety of central compartment neck dissection for transoral endoscopic thyroid surgery in papillary thyroid carcinoma.

BACKGROUND: Remote access and endoscopic thyroid surgery has been gaining popularity because it allows patients to avoid a visible scar in the neck. There is limited data on transoral endoscopic thyroidectomy when it relates to patients with papillary thyroid carcinoma. We aim to evaluate the safety of ipsilateral central compartment dissection for patients who undergo transoral thyroidectomy (thyroidectomy vestibular approach-compartment lymph node dissection). PATIENTS AND METHODS: A total of 80 patients who underwent thyroidectomy vestibular approach-compartment lymph node dissection for papillary thyroid carcinoma from June 2015 to September 2016 were identified. Over the same period, a matched cohort of 80 patients who underwent open thyroidectomy with routine ipsilateral central compartment dissection was also identified (Open-compartment lymph node dissection). The two groups were analyzed in terms of patient characteristics, perioperative clinical results and post-operative outcomes. RESULTS: All patients were female with a mean age of 32-year. There was no difference in mean maximum tumor size and number of lymph nodes dissected. Moreover, there was no difference in average positive lymph nodes between thyroidectomy vestibular approach-compartment lymph node dissection and Open-compartment lymph node dissection (1.48 vs 1.08, P = 0.647). Operative time was longer in the thyroidectomy vestibular approach-compartment lymph node dissection group (193 vs 102 min, P < 0.001). Thyroidectomy specific complications were similar with rates of temporary recurrent laryngeal nerve palsy of 6.3 vs 8.8% and temporary hypocalcemia rates of 2.5 vs 5% in the thyroidectomy vestibular approach-compartment lymph node dissection and Open-compartment lymph node dissection groups, respectively. CONCLUSIONS: Thyroidectomy vestibular approach-compartment lymph node dissection is a feasible and safe option for select patients with papillary thyroid carcinoma who require central node dissection compared with Open-compartment lymph node dissection, and can be a viable alternative for patients wishing to avoid a visible scar.

Defining a New Tumor Dimension in Staging of Papillary Thyroid Carcinoma.

BACKGROUND: Cervical lymph node metastasis is a vital factor associated with local recurrence in papillary thyroid carcinoma (PTC). Tumor size is used in the staging of PTC because it represents the tumor load. This study compared two methods of tumor size assessment to predict tumor behavior in the relationship between size and cervical node involvement for patients with PTC. METHODS: The study enrolled 1084 patients who underwent initial thyroid surgery and had a pathologic diagnosis of PTC between 2012 and 2014 at The Second Affiliated Hospital Zhejiang University School of Medicine. Cervical lymph node metastasis (LNM) risk was analyzed according to the clinicopathologic features. For each patient with multifocal disease, two tumor size estimates were used: (1) the dominant focus size and (2) the aggregate size, calculated as the sum of the maximal diameters of all tumor foci. RESULTS: Of the 1084 patients, 294 (27.1%) had multifocal cancer lesions, and 49% of these patients had cervical LNM, compared with 38.1% who had unifocal disease (P = 0.001). The use of aggregate dimension significantly increased the tumor size and reclassified significant numbers of multifocal PTCs to a more advanced T stage. This aggregate dimension took account of all tumor foci and predicted LNM risk at a proportion identical with that for size-matched, unifocal tumors. CONCLUSION: Multifocality together with aggregate tumor size is a more accurate predictor of node status and, by inference, tumor behavior in the relationship between tumor size and cervical node involvement.

"Scarless" (in the neck) endoscopic thyroidectomy (SET) with ipsilateral levels II, III, and IV dissection via breast approach for papillary thyroid carcinoma: a preliminary report.

BACKGROUND: Endoscopic thyroidectomy with level II dissection has previously been reported to be performed endoscopically via various approaches. However, very few reports were available regarding level II dissection performed via the breast approach. In this article, we reported a series of 12 papillary thyroid carcinoma (PTC) patients with scarless (in the neck) endoscopic thyroidectomy (SET) via breast approach to level II dissection and evaluated its feasibility and safety. METHODS: Between January 2011 and March 2013, 12 PTC female patients with suspected lymph node metastasis at level II, III, or IV were selected for this procedure. After completing thyroidectomy and central compartment dissection, dissection of ipsilateral levels II, III, and IV was performed. The steps of endoscopic lateral neck dissection were similar to those of conventional surgery except that the lateral cervical compartment was exposed by splitting the sternocleidomastoid muscle (SCM) longitudinally and dividing between the strap muscles and the anterior margin of the SCM. RESULTS: This procedure was carried out in all of the 12 patients (Table 1). Mean operative time was 243 min (range 165-355 min). Nine patients (75 %) had lymph node metastasis in the lateral compartment confirmed on the final pathological report. Mean lymph node yield (LNY) in the lateral compartment (including ipsilateral level II, III, and IV dissection) was 21.8 (range 5-42). Five patients (41.6 %) had lymph node metastasis in the ipsilateral level II. The mean LNY in the ipsilateral level II was 6.7 (range 1-14). In 1 of the 12 patients, bleeding from injury to the internal jugular vein in level II was encountered intraoperatively, and a 4-cm upper neck transverse incision was made to stop the bleeding. Average postoperative hospital stay was 5.0 days (range 3-7 days). Table 1 Original article on endoscopic lateral neck dissection (including level II) by other authors Author (Ref.) Year Mean age (years) Tumor size (cm) No. of patients M:F Tech. Type of operation Mean LNY in lateral zone Mean operative time (min) Postoperative bleeding Chyle leakage Mean PHS (days) Wu et al. [13] 2013 43.2 1.88 26 6:20 VAT SLND 8.3 137.7 None None 3.6 Lee et al. [8] 2013 40.2 1.39 62 5:57 Robot MRND 32.8 271.8 None None 6.9 Kang et al. [5] 2012 35.8 1.14 56 10:46 Robot MRND 31.1 277.4 1 5 6 Kang et al. [6] 2011 NA NA 36 NA Robot MRND 27.7 280.91 1 3 NA Kang et al. [4] 2009 NA NA 13 NA AP MRND/SLND 18.8 286 NA NA 5.3 Current article 31.2 1.67 12 0:12 SET SLND 21.8 243 None None 5 Ref. references, No. number, M male, F female, Tech. technique, LNY lymph node yield, PHS postoperative hospital stay, VAT video-assisted thyroidectomy, SLND selective lateral neck dissection, MRND modified radical neck dissection, AP axillary approach, NA not available CONCLUSIONS: According to the present SET data, level II dissection by SET was a feasible and safe procedure. With reasonable costs and satisfactory cosmetic results, oncoplastic SET via breast approach might gain wider acceptance in the near future.

[Three-dimensional total endoscopic thyroidectomy for thyroid carcinoma: a series of 32 cases].

OBJECTIVE: To summarize the experiences of applying three-dimensional (3D) technique in scarless endoscopic thyroidectomy (SET) via anterior chest approach. METHODS: Medical records of patients who undenvent SET using 3D technique from December 2013 to May 2014 were retrospectively reviewed. A total of 32 patients who had a preoperative ultrasound-guided fine-needle aspiration cytology diagnosis of unilateral papillary thyroid carcinoma and underwent lobectomy associated with central lymph node dissection were included in this study. All patients were female with a mean age of (37 ± 10) years at diagnosis. In addition, 45 female patients who underwent traditional endoscopic thyroidectomy at the same period were randomly selected as control. RESULTS: All surgical procedures were successfully finished. The mean surgical time in 3D group was (91. 7 ± 11. 4) minutes, and mean hospitalization time was (3. 2 ± 0. 5) days. Contemporary hoarseness was observed in one patient, and no bleeding, infection, hypocalcemia and other postsurgical complications were observed. Compared to the traditional endoscopic surgery group, 3 D group had significantly shorter surgical time of lobectomy ((23. 2 ± 5. 1) minutes vs. (28. 0 ± 5. 0) minutes, t = 4. 156, P = 0. 000). Negative results were seen in the time taking of creating surgical space ((14. 6 ± 3. 3) minutes vs. (15. 6 ± 2. 5) minutes), central lymph node dissection ((25. 1 ± 5. 4) minutes vs. (24. 4 ± 6. 3) minutes) and total surgical time ((91.7 ± 11. 4) minutes vs. (96. 1 ± 13. 0) minutes). CONCLUSION: Application of 3D technique in endoscopic surgery can offer 3D vision of the surgical field, thus significantly shorten lobectomy time and more easily to achieve fine dissection and functional protection of recurrent laryngeal nerves, parathyroids and other vital anatomic structures.

Genetic variation in the major mitotic checkpoint genes and risk of breast cancer: a multigenic study on cancer susceptibility.

The mitotic checkpoint system is a mechanism essential for maintaining genomic stability and defects which have been linked to cancer development. We conducted this hospital-based case-control study to investigate whether genetic variants in three major spindle checkpoint genes (BUB3, MAD2L1, and BUB1) had any bearing on an individual risk of breast cancer (BC). A total of 462 incident BC patients and 529 cancer-free controls were enrolled in this study. Results showed that neither variants in BUB3 nor variants in MAD2L1 caused any significant effect on the risk of BC. However, the variant rs12623473 in BUB1 was significantly associated with increased BC risk with the odds ratio (OR) of 1.30 (95 % confidence interval (CI) 1.03-1.64) under the allelic model. The estimated population attributable risk of one copy of the risk allele for developing BC was 10.3 %. The bioinformatics analysis suggested that this variant may regulate the transcriptional ability of BUB1.

Effects of Stir-Frying and Heat-Moisture Treatment on the Physicochemical Quality of Glutinous Rice Flour for Making Taopian, a Traditional Chinese Pastry.

Taopian is a traditional Chinese pastry made from cooked glutinous rice flour. The effects of heat-moisture treatment (110 °C, 4 h; moisture contents 12-36%, w/w) on the preparation of cooked glutinous rice flour and taopian made from it were compared with the traditional method of stir-frying (180 °C, 30 s). The color of heat-moisture-treated (HMT) flours was darker. HMT flours exhibited a larger mean particle size (89.5-124 µm) and a greater relative crystallinity of starch (23.08-42.92%) and mass fractal dimension (1.77-2.28). The flours exhibited water activity in the range of 0.589-0.631. Although the oil-binding capacity of HMT flours was largely comparable to that of stir-fried flours, HMT flours exhibited a lower water absorption index. Accordingly, the taopian produced with HMT flours exhibited a lower brightness, accompanied by a stronger reddening and yellowing. In addition, more firmly bound water was observed in the taopian produced with HMT flour. The taopian made with HMT flour with a moisture content of 24% exhibited moderate hardness, adhesiveness and cohesiveness and received the highest score for overall acceptability (6.80). These results may be helpful to improve the quality of taopian by applying heat-moisture treatment in the preparation of cooked glutinous rice flour.

Controlled Self-Assembly of Natural Polyphenols Driven by Multiple Molecular Interactions.

Nature has exhibited a high degree of control over the structures and functions. Supramolecules have been utilized to mimic the subtle assembly in nature. However, sophisticated synthesis of molecular skeletons or programmable design of the driving forces raises great challenges in fabricating high-level superstructures in a controlled manner. Natural polyphenols show great promises as building blocks for a diverse of assemblies with controlled structures and functionalities. The intrinsically embedded phenolic groups (i. e., catechol and galloyl groups) are readily forming multiple molecular interactions, including coordination, hydrogen bonding, and π-π interactions with various materials of inorganic particles, organic compounds, synthetic polymers, and biomacromolecules, providing the self-assembled structures or nanocoating on surfaces. Subsequent assembly occurred by further bonding of polyphenols to construct supraparticles. To gain control over the self-assembly, the key lies in the interplay among the molecular interactions with one or two being dominant. In this Perspective, we introduce the representative polyphenol-based assemblies and their derived supraparticles to exhibit the effective harness of the controlled self-assembly by polyphenols.

Feasibility and safety of modified en-bloc resection in endoscopic thyroid surgery via bilateral areolar approach - long-term institutional analysis ten years after surgery.

Purpose: This study aimed to introduce a new modified en-bloc resection method and evaluate its feasibility and safety in endoscopic thyroid surgery via bilateral areolar approach (BAA). Methods: Papillary thyroid carcinoma (PTC) patients who underwent lobectomy and ipsilateral central node dissection (CND) via the BAA approach were retrospectively reviewed. Their clinical characteristics and outcomes were evaluated, including operative duration, lymph node yield (LNY), surgical complications, recurrence rate, and metastasis rate, over a ten-year follow-up period. Simultaneous lobectomy and CND were performed in the modified en-bloc group, whereas lobectomy was performed first, followed by CND in the conventional group. Results: The study included 108 patients in the modified en-bloc group and 213 in the conventional group. There were no significant differences in gender, age, tumor locations, tumor dominant nodule size, or the incidence of concomitant Hashimoto thyroiditis when comparing clinicopathologic characteristics. The comparison of operative duration (P = 0.14), blood loss (P = 0.13), postoperative hospital stay (P = 0.58), incidence of transient vocal cord paralysis (P = 0.90) and hypocalcemia (P = 0.60) did not show any differences. The mean LNY achieved in the central compartment of the modified en-bloc group (7.5 ± 4.5) was significantly higher than that in the conventional group (5.6 ± 3.6). Two patients in the modified en-bloc group and two in the conventional group experienced metastasis after surgery during the ten-year follow-up (1.8% vs. 0.9%, P = 0.60). The learning curve analysis showed a significant decrease in operative duration after the 25-35th cases for modified en-bloc resection. Conclusions: The modified en-bloc resection method in endoscopic thyroid surgery via BAA is a technically feasible and safe procedure with excellent cosmetic outcomes for selective PTC patients.

Hydrogen-bonded supramolecular biohybrid frameworks for protein biomineralization constructed from natural phenolic building blocks.

Hydrogen bond-mediated supramolecular crystalline materials, such as hydrogen-bonded organic frameworks, offer a promising strategy for protein biomineralization, yet the intricate design and multi-step synthesis of specific orthogonal units in molecular building blocks pose a significant synthetic challenge. Identifying new classes of natural building blocks capable of facilitating supramolecular framework construction while enabling stable protein binding has remained an elusive goal. Here, we introduce a versatile assembly strategy enabling the organization of diverse proteins and phenolic building blocks into highly crystalline hydrogen-bonded supramolecular phenolic frameworks (ProteinX@SPF). The natural ellagic acid (EA) exhibits a centrosymmetric structure with catechol groups on each molecular side, facilitating hydrogen bonding with protein amino acid residues for primary nucleation. Subsequently, EA self-assembles into ProteinX@SPF through hydrogen bonding and π-π interactions. The multiple hydrogen-bonding interactions impart structural rigidity and directional integrity, conferring ProteinX@SPF biohybrids with remarkable resistance to harsh conditions while preserving protein bioactivity. Additionally, the supramolecular stacking induced by π-π interactions endows ProteinX@SPF with long-range ordered nanochannels, which can serve as the gating to sieve the catalytic substrate and thus enhance the biocatalytic specificity. This work sheds light on biomineralization with natural building blocks for functional biohybrids, showing enormous potential in biocatalysis, sensing, and nanomedicine.

Ten cancer associated genes identified in peripheral blood mononuclear cells from patients with pancreatic adenocarcinoma.

BACKGROUND/AIMS: Identification of biomarkers for pancreatic cancer may help diagnosis and treatment of patients. METHODOLOGY: This pilot study evaluated potential markers for pancreatic adenocarcinoma (PAC) in peripheral blood mononuclear cells (PBMC). RNA samples were isolated from PBMCs and hybridized to oligonucleotide arrays. RESULTS: Twenty five-fold leave-two-out analysis identified 10 cancer-associated genes (CAGs). The PAC patients could be identified by the expression profiles of their PBMC with a specificity of 96% and a sensitivity of 80%. CONCLUSIONS: Ten CAGs were potential new markers in PBMC for patients with PAC.

A novel microRNA panel exhibited significant potential in evaluating the progression of laryngeal squamous cell carcinoma.

Background: Laryngeal squamous cell carcinoma (LSCC) is a common cancer of the head and neck in humans. The 5-years survival rate of patients with LSCC have declined in the past four decades. microRNAs (miRNAs) has been reported to be capable of predicting the prognosis outcomes of patients with different cancers. However, there are no reports on the usage of multi-miRNAs model as signature for the diagnosis or prognosis of LSCC. Methods: To establish the miRNAs expression-associated model for diagnosis, prognosis prediction and aided therapy of patients with LSCC, the present study enrolled 107 patients with LSCC in clinic and obtained 117 LSCC samples data from TCGA database for evaluation, respectively. Next generation sequencing (NGS), raw data processing, the least absolute shrinkage and selection operator algorithm, Cox regression analysis, construction of nomogram and cell function assays (including proliferation, migration and invasion assays) were sequentially performed. Results: There were massively dysregulated miRNAs in the LSCC compared to normal tissues. A six-miRNAs signature consists of miR-137-3p, miR-3934-5p, miR-1276, miR-129-5p, miR-7-5p and miR-105-5p was built for prognosis prediction of LSCC patients. The six-miRNAs signature is strongly associated with the poor overall survival (OS, p = 2.5e-05, HR: 4.30 [2.20-8.50]), progression free interval (PFI, p = 0.025, HR: 1.94 [1.08-3.46]) and disease specific survival (DSS, p = 1.1e-05, HR: 5.00 [2.50-10.00]). A nomogram for prediction of 2-, 3- and 5-years OS was also developed based on the six-miRNAs signature and clinical features. Furthermore, blocking the function of each of the six miRNAs inhibited proliferation, invasion and migration of LSCC cells. Conclusions: The performance of six-miRNAs signature described in the current study demonstrated remarkable potential for progression assessment of LSCC. Moreover, the six-miRNAs signature may serve as predictive tool for prognosis and therapeutic targets of LSCC in clinic.

The divergent protective effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on clinical outcomes of coronavirus disease 2019 (COVID-19): a systematic review and meta-analysis.

BACKGROUND: Some studies have speculated that patients on angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) are more susceptible to adverse outcomes of coronavirus disease 2019 (COVID-19). Here, we performed a systematic review and meta-analysis to evaluate the safety and efficacy of administering ACEIs and ARBs to patients with COVID-19. METHODS: Studies of COVID-19 were collected from the PubMed, Embase, medRxiv and BioRxiv databases. The pooled relative risk odds ratio (OR) and 95% confidence interval (95% CI) were calculated. Subgroup analyses were conducted by medication (ACEIs and ARBs) and geographical location (China and outside China). Inter-study heterogeneity was assessed using meta-regression. Begg's test, Egger's test and funnel plots were adopted to evaluate possible publication bias. RESULTS: Thirty studies containing 10,434 adult patients were included in our meta-analysis. The pooled result indicated that the administration of ACEIs or ARBs reduced the risk of severe/death outcomes for COVID-19 patients. Meanwhile, a significant reduction in the risk of severe/death outcomes was observed to be associated with the administration of ACEIs or ARBs among COVID-19 patients in China, but this association was weaker for studies outside China. Furthermore, ACEI therapy was found to carry a significantly lower risk of an adverse clinical outcome. DISCUSSION: Our systematic review and meta-analysis found that neither ACEIs nor ARBs worsen the clinical outcomes of COVID-19 patients. On the contrary, we found that patients treated with ACEIs or ARBs have a reduced risk of severe/death outcomes, especially in Asia. Furthermore, ACEIs may reduce the risk of severe/death outcomes. Therefore, treatment interruption of ACEI or ARB therapy during COVID-19 infection is not recommended.

Increased expression level of Olfactomedin4 in peripheral blood mononuclear cells of pancreatic adenocarcinoma patients.

BACKGROUND/AIMS: To identify potential new tumor markers in peripheral blood mononuclear cells for pancreatic adenocarcinoma screening. METHODOLOGY: The total mRNA was extracted from the peripheral blood mononuclear cell samples of both pancreatic adenocarcinoma patients (n=5) and healthy donors (n=5). Having the RNA expression profiling of over 38500 genes via the Human Genome U133 Plus 2.0 Array performed in order to identify differentially expressed genes, the study underwent real-time Reverse Transcriptase PCR (RT-PCR) for validation. RESULTS: The mRNA expression profiles identified the Olfactomedin4 gene, which was significantly overexpressed (4.46-fold) versus the control group (p<0.01). Afterwards, this result was validated by quantitative RT-PCR, with the same expression trend (4.80-fold) as well as statistical significance (p<0.05). CONCLUSIONS: Homo sapiens olfactomedin4 was revealed to be up-regulated as a cancer associated gene in peripheral blood mononuclear cells from pancreatic adenocarcinoma patients. Thus, Olfactomedin4, as well as its expression products, might promisingly prove to be the ideal screening tool and new tumor marker available in blood samples.

Percutaneous coronary intervention versus coronary artery bypass grafting in patients with coronary heart disease and type 2 diabetes mellitus: Cumulative meta-analysis.

Previous meta-analyses showed that coronary artery bypass grafting (CABG) has lower all-cause mortality than percutaneous coronary intervention (PCI) for the management of coronary heart disease (CHD), but the long-term outcomes were not analyzed thoroughly in patients with type 2 diabetes mellitus (T2DM). To perform a meta-analysis of randomized controlled trials (RCTs) to explore the long-term effectiveness between CABG and PCI in patients with T2DM and study the temporal trends using a cumulative meta-analysis. PubMed, Embase, Cochrane library, and Clinical Trials Registry for eligible RCTs published up to September 2020. The outcomes were all-cause death, cardiac death, myocardial infarction, repeat revascularization, and stroke. Nine RCTs and 4566 patients were included. CABG resulted in better outcomes than PCI in terms of all-cause death (RR = 1.41, 95%CI: 1.22-1.63, p < 0.001), cardiac death (RR = 1.56, 95%CI: 1.25-1.95, p < 0.001), and repeat revascularization (RR = 2.68, 95%CI: 1.86-3.85, p < 0.001), but with difference regarding the occurrence of myocardial infarction (RR = 1.20, 95%CI: 0.78-1.85, p = 0.414), while PCI was associated with better outcomes in terms of stroke occurrence (RR = 0.51, 95%CI: 0.34-0.77, p = 0.001). The cumulative meta-analysis for all-cause death showed that the differences between CABG and PCI started to be significant at 3 years of follow-up, while the difference became significant at 5 years for cardiac death. In patients with CHD and T2DM, CABG results in better outcomes than PCI in terms of all-cause death, cardiac mortality, and repeat revascularization, while PCI had better outcomes in terms of stroke. The differences are mainly observed over the long-term follow-up.

Human bone marrow mesenchymal stem cells differentiate into insulin-producing cells upon microenvironmental manipulation in vitro.

It was recently reported that pluripotent mesenchymal stem cells (MSCs) in rodent bone marrow (BM) have the capacity to generate insulin-producing cells (IPCs) in vitro. However, little is known about this capacity in human BM-MSCs. We developed a nongenetic method to induce human BM-MSCs to transdifferentiate into IPCs both phenotypically and functionally. BM-MSCs from 12 human donors were sequentially cultured in specially defined conditions. Their differentiation extent toward beta-cell phenotype was evaluated systemically. Specifically, after induction human BM-MSCs formed spheroid islet-like clusters containing IPCs, which was further confirmed by dithizone (DTZ) staining and electron microscopy. These IPCs expressed multiple genes related to the development or function of pancreatic beta cells (including NKX6.1, ISL-1, Beta2/Neurod, Glut2, Pax6, nestin, PDX-1, ngn3, insulin and glucagon). The coexpression of insulin and c-peptide was observed in IPCs by immunofluorescence. Moreover, they were able to release insulin in a glucose-dependent manner and ameliorate the diabetic conditions of streptozotocin (STZ)-treated nude mice. These results indicate that human BM-MSCs might be an available candidate to overcome limitations of islet transplantation.

Beyond temperature: controlling collagen fibrillogenesis under physiological conditions via interaction with cucurbit[7]uril.

Under physiological ionic strength and pH, temperature has long been appreciated as the only stimulus that can be applied to induce in vitro self-assembly of tropocollagen. Here, we report a second, mechanistically new control strategy that uses non-covalent and selective binding of cucurbit[7]uril, a macrocyclic cavitand, with midchain aromatic residues on the tropocollagen surface. This strategy directly demonstrates the decisive role hydrophobic interactions play in collagen fibrillogenesis. It also points the way to the temporally-controllable formation of collagen fibrils in vivo that is highly desirable, yet challenging, in some biomedical scenarios.

Thyroid paraganglioma accompanied by lymph node metastasis or trachea invasion: A case report.

Thyroid paraganglioma (TP) is an uncommon neuroendocrine tumor with potential for misdiagnosis. Case 1 (male; 44 years old) presented with hoarseness for 3 months. A 2.5-cm gray nodule in the left thyroid was diagnosed as TP by immunohistochemistry. Lymph node metastasis was confirmed by H&E staining and immunohistochemistry. The patient was followed-up for 3 years without any signs of recurrence or metastasis. Case 2 (female; 39 years old) presented with an asymptomatic but rapidly growing thyroid nodule. The patient underwent thyroidectomy 8 years ago (2008) and was diagnosed with TP postoperatively. The patient was diagnosed with recurrence and exhibited trachea invasion. Thyroidectomy and partial trachea resection were performed. A literature review revealed that 62 other cases of TP have been reported, and most of them exhibited low malignant potential. However, the two cases presented in the current case report exhibited a high malignant potential, accompanied by lymph node metastasis or trachea invasion, and these features imply that the choice of treatment for patients should be based on their different degrees of malignancy.

CRISPR/Cas9-Based Genome Editing in the Filamentous Fungus Glarea lozoyensis and Its Application in Manipulating gloF.

Glarea lozoyensis is an important industrial fungus that produces the pneumocandin B0, which is used for the synthesis of antifungal drug caspofungin. However, because of the limitations and complications of traditional genetic tools, G. lozoyensis strain engineering has been hindered. In this study, we established an efficient CRISPR/Cas9-based gene editing tool in G. lozoyensis SIPI1208. With this method, gene mutagenesis efficiency in the target locus can be up to 80%, which enables the rapid gene knockout. According to the reports, GloF and Ap-HtyE, proline hydroxylases involved in pneumocandin and Echinocandin B biosynthesis, respectively, can catalyze the proline to generate different ratios of trans-3-hydroxy-l-proline to trans-4-hydroxy-l-proline. Heterologous expression of Ap-HtyE in G. lozoyensis decreased the ratio of pneumocandin C0 to (pneumocandin B0 + pneumocandin C0) from 33.5% to 11% without the addition of proline to the fermentation medium. Furthermore, the gloF was replaced by ap-htyE to study the production of pneumocandin C0. However, the gene replacement has been hampered by traditional gene tools since gloF and gloG, two contiguous genes indispensable in the biosynthesis of pneumocandins, are cotranscribed into one mRNA. With the CRISPR/Cas9 strategy, ap-htyE was knocked in and successfully replaced gloF, and results showed that the knock-in strain retained the ability to produce pneumocandin B0, but the production of pneumocandin C0 was abolished. Thus, this strain displayed a competitive advantage in the industrial production of pneumocandin B0. In summary, this study showed that the CRISPR/Cas9-based gene editing tool is efficient for manipulating genes in G. lozoyensis.