The role of alternative splicing in lung cancer.

Aberrant alternative splicing (AS) events are frequently observed in lung cancer, which can be attributed to aberrant gene AS, alterations in splicing regulatory factors, or changes in splicing regulatory mechanisms. Consequently, the dysregulation of alternative RNA splicing is the fundamental cause of lung cancer. In this review, we have summarized the pivotal role of AS in the development, progression, invasion, metastasis, angiogenesis, and drug resistance of lung cancer. Ultimately, this review emphasizes the potential of AS as biomarkers in lung cancer prognosis and diagnosis, and introduces some applications of AS isoform in the treatment of lung cancer. The comprehension of the AS may provide a glimmer of hope for the eradication of lung cancer.

Metabolic Engineering of Saccharomyces cerevisiae for Vitamin B5 Production.

Vitamin B5, also called d-pantothenic acid, is an essential vitamin in the human body and is widely used in pharmaceuticals, nutritional supplements, food, and cosmetics. However, few studies have investigated the microbial production of d-pantothenic acid, especially in Saccharomyces cerevisiae. By employing a systematic optimization strategy, we screened seven key genes in d-pantothenic acid biosynthesis from diverse species, including bacteria, yeast, fungi, algae, plants, animals, etc., and constructed an efficient heterologous d-pantothenic acid pathway in S. cerevisiae. By adjusting the copy number of the pathway modules, knocking out the endogenous bypass gene, balancing NADPH utilization, and regulating the GAL inducible system, a high-yield d-pantothenic acid-producing strain, DPA171, which can regulate gene expression using glucose, was constructed. By optimizing fed-batch fermentation, DPA171 produced 4.1 g/L d-pantothenic acid, which is the highest titer in S. cerevisiae to date. This study provides guidance for the development of vitamin B5 microbial cell factories.

A Novel Strategy for Excellent Piezocatalytic Activity in Lead-Free BaTiO3-Based Materials via Manipulating the Multiphase Coexistence.

Piezocatalysis is regarded as a fascinating technology for water remediation and possible disease treatment. A high piezoelectric coefficient (d33) is one of the most important parameters to determine piezocatalytic performance, which can be manipulated via phase boundary design. Herein, a novel strategy for excellent piezocatalytic activity in lead-free BaTiO3-based materials via manipulating the multiphase coexistence is proposed. The piezocatalyst of 0.82Ba(Ti0.89Sn0.11)O3-0.18(Ba0.7Ca0.3)TiO3 (0.82BTS-0.18BCT) with multiphase coexistence is prepared, and a large d33 can be obtained. As a result, 0.82BTS-0.18BCT exhibits excellent piezocatalytic performance for the degradation of Rhodamine B (RhB). Furthermore, the removal rate of RhB could reach more than 90% after vibration for 30 min, and the reaction rate constant (k) could reach 0.0706 min-1, which is much superior to that of most other representative perovskite-structured piezoelectric materials. Excellent piezocatalytic performance can be attributed to the strong local ferro-/piezoelectric response induced by the multiphase coexistence, as confirmed by the in situ piezoresponse force microscopy (PFM). Finally, the piezocatalytic degradation mechanism is analyzed systemically and proposed. This work not only provides a high-efficiency piezocatalyst but also sheds light on developing efficient BT-based piezocatalysts by manipulating the multiphase coexistence.

Metabolic pathway assembly using docking domains from type I cis-AT polyketide synthases.

Engineered metabolic pathways in microbial cell factories often have no natural organization and have challenging flux imbalances, leading to low biocatalytic efficiency. Modular polyketide synthases (PKSs) are multienzyme complexes that synthesize polyketide products via an assembly line thiotemplate mechanism. Here, we develop a strategy named mimic PKS enzyme assembly line (mPKSeal) that assembles key cascade enzymes to enhance biocatalytic efficiency and increase target production by recruiting cascade enzymes tagged with docking domains from type I cis-AT PKS. We apply this strategy to the astaxanthin biosynthetic pathway in engineered Escherichia coli for multienzyme assembly to increase astaxanthin production by 2.4-fold. The docking pairs, from the same PKSs or those from different cis-AT PKSs evidently belonging to distinct classes, are effective enzyme assembly tools for increasing astaxanthin production. This study addresses the challenge of cascade catalytic efficiency and highlights the potential for engineering enzyme assembly.

Osteoporosis, fracture and survival: Application of machine learning in breast cancer prediction models.

The risk of osteoporosis in breast cancer patients is higher than that in healthy populations. The fracture and death rates increase after patients are diagnosed with osteoporosis. We aimed to develop machine learning-based models to predict the risk of osteoporosis as well as the relative fracture occurrence and prognosis. We selected 749 breast cancer patients from two independent Chinese centers and applied six different methods of machine learning to develop osteoporosis, fracture and survival risk assessment models. The performance of the models was compared with that of current models, such as FRAX, OSTA and TNM, by applying ROC, DCA curve analysis, and the calculation of accuracy and sensitivity in both internal and independent external cohorts. Three models were developed. The XGB model demonstrated the best discriminatory performance among the models. Internal and external validation revealed that the AUCs of the osteoporosis model were 0.86 and 0.87, compared with the FRAX model (0.84 and 0.72)/OSTA model (0.77 and 0.66), respectively. The fracture model had high AUCs in the internal and external cohorts of 0.93 and 0.92, which were higher than those of the FRAX model (0.89 and 0.86). The survival model was also assessed and showed high reliability via internal and external validation (AUC of 0.96 and 0.95), which was better than that of the TNM model (AUCs of 0.87 and 0.87). Our models offer a solid approach to help improve decision making.

Focal IgG4-related autoimmune pancreatitis with distal choledochal adenocarcinoma: a rare case report.

BACKGROUND: Autoimmune pancreatitis (AIP) is a rare disease that manifests as pancreatic involvement in systemic IgG4-related disease (IgG4-RD), a special type of chronic pancreatitis caused by autoimmune abnormalities. The main imaging manifestations of IgG4-related AIP consist of diffuse or localized pancreatic enlargement and irregular pancreatic duct narrowing. The diagnosis of AIP is challenging because it can present with focal lesions, similar to radiologically bile duct cancer or pancreatic cancer. CASE PRESENTATION: A 55-year-old male patient was admitted with painless jaundice and multiple radiographic findings of pancreatic head mass, as well as intrahepatic and extrahepatic bile duct dilatation. Various imaging methods indicated pancreatic cancer. However, the endoscopic ultrasonography guided fine needle aspiration (EUS-FNA) and a laparoscopic pancreatic biopsy suggested an IgG4-related AIP. After one month, magnetic resonance imaging showed that the lesion had slightly grown. Combined with CA19-9 and other indexes, the possibility of malignancy was high and there were still surgical indications. The pathological analysis following a pancreaticoduodenectomy revealed poorly differentiated adenocarcinoma in the distal common bile duct. CONCLUSION: To date, few reports have described pancreatic or extrapancreatic malignancies in AIP patients, and no association between AIP and bile duct adenocarcinoma has been previously confirmed. This case discuss the differentiation between AIP and malignancy, recent research progress, and the correlation between the two diseases, highlights the importance of carefully evaluating patients with AIP to rule out potential tumors, as well as the critical need for follow up treatment.

Widowhood and Life Satisfaction Among Chinese Elderly Adults: The Influences of Lifestyles and Number of Children.

Our study examined how lifestyle and number of children influence the relationship between widowhood and life satisfaction based on self-regulation theory. A sample of 2,968 elderly respondents (male = 1,515, female = 1,453, mean age = 69.12 years, SD = 7.24) participated in Chinese General Social Survey. Our findings suggest that lifestyle is positively related to life satisfaction, and number of children is positively associated with life satisfaction but negatively related to lifestyle. The moderated mediation model demonstrated that lifestyle partly mediated the relationship between widowhood and life satisfaction. Moreover, number of children moderated the relationship between widowhood and lifestyle and between lifestyle and satisfaction with life. Widowed elderly individuals who have more children are likely to show a higher level of satisfaction with life. The present study has significance in practice because it provides empirical implications obtained from a national survey on the universal two-child policy in China as two children might decrease the negative impacts of widowhood on life satisfaction.

Application of curved ablation in liver cancer with special morphology or location: Report of two cases.

BACKGROUND: Liver cancer is one of the most common malignant tumors with a high incidence and mortality. Hepatitis-liver cirrhosis-liver cancer is known as the trilogy of liver cancer. At present, due to significant development of imaging interventions, they occupy an irreplaceable position in the field of liver cancer treatment, especially ultrasound-guided ablation. Because patients with liver cancer often present with liver cirrhosis, which leads to morphological deformation of the liver, it is difficult to perform a linear ablation of liver cancer in the areas near the phrenic top and within large blood vessels, among others. The present study reports on two cases of liver cancer that have been subjected to curvilinear ablation. After 1 mo, magnetic resonance imaging showed complete ablation, demonstrating that ultrasound-guided curved ablation is feasible and effective in the treatment of liver cancer. CASE SUMMARY: Two patients were treated at the Liver Disease Department of the Xixi Hospital Affiliated to Zhejiang University of Chinese Medicine in 2019. Because the first liver cancer patient's tumor was located close to the diaphragm, it was difficult to complete a straight needle ablation procedure in one session. In order to achieve accurate and minimally invasive treatment of this tumor, a curved needle ablation procedure was designed. The second patient presented with a hepatic cyst in front of the tumor. In order not to damage the hepatic cyst, a looper needle ablation technique was used. The procedure was successfully completed in both cases. CONCLUSION: Curved ablation is a new technique that can be used to treat tumors situated in a variety of locations, providing new ideas for interventional techniques. Its operation difficulty is higher and further animal experiments are necessary to improve the operation procedure.

Peutz-Jeghers syndrome with mesenteric fibromatosis: A case report and review of literature.

BACKGROUND: Peutz-Jeghers syndrome (PJS) and mesenteric fibromatosis (MF) are rare diseases, and PJS accompanying MF has not been previously reported. Here, we report a case of a 36-year-old man with both PJS and MF, who underwent total colectomy and MF surgical excision without regular follow-up. Two years later, he sought treatment for recurrent acute abdominal pain. Emergency computed tomography showed multiple soft tissue masses in the abdominal and pelvic cavity, and adhesions in the small bowel and peritoneum. Partial intestinal resection and excision of the recurrent MF were performed to relieve the symptoms. CASE SUMMARY: A 36-year-old male patient underwent total colectomy for PJS with MF. No regular reexamination was performed after the operation. Two years later, due to intestinal obstruction caused by MF enveloping part of the small intestine and peritoneum, the patient came to our hospital for treatment. Extensive recurrence was observed in the abdomen and pelvic cavity. The MF had invaded the small intestine and could not be relieved intraoperatively. Finally, partial bowel resection, proximal stoma, and intravenous nutrition were performed to maintain life. CONCLUSION: Regular detection is the primary way to prevent deterioration from PJS. Although MF is a benign tumor, it has characteristics of invasive growth and ready recurrence. Therefore, close follow-up of both the history of MF and gastrointestinal surgery are advisable. Early detection and early treatment are the main means of improving patient prognosis.

Dermatofibrosarcoma metastases to the pancreas: A case report.

BACKGROUND: In general, malignant tumors metastasize to the pancreas in < 1% of cases. Most patients miss the opportunity for further surgery due to distant metastases; however, for fibrosarcomas, aggressive surgery may be helpful even if distant metastases occur. Hence, we report such a case and share some valuable information about the disease. CASE SUMMARY: A 45-year-old man was admitted with recurrent epigastric pain for 10 days. The abdominal pain was mainly related to bloating with nausea, but no other associated symptoms. No particular signs were found on abdominal examination or laboratory testing. In 2003, a local distal expanded resection of the primary fibrosarcoma in the left chest wall was performed. Then, a left pneumonectomy was performed in 2017 due to diffuse metastases from the fibrosarcoma to the left lung. Enhanced computed tomography (CT) and magnetic resonance imaging of the upper abdomen suggested multiple masses of different sizes involving the head and tail of the pancreas; no local lymph node enlargement was noted. The postoperative pathologic diagnosis revealed a fibrosarcoma of the pancreas. A CT re-examination 6 mo postoperatively showed no local recurrence or distant metastases. CONCLUSION: A fibrosarcoma is a rare low-grade malignant tumor, and metastases to the pancreas are even rarer. Patients with a history of a fibrosarcoma should consider the possibility of metastasis when a pancreatic neoplasm is demonstrated. Surgical resection is the preferred treatment.

Primary renal synovial sarcoma: A case report.

BACKGROUND: Synovial sarcoma, a rare mesenchymal tumor type with unclear histological origin and direction of differentiation, accounts for 6%-10% of soft tissue tumors. It is mainly located near the joints and tendons of the limbs, and occurs primarily in children or young adults. Primary renal synovial sarcoma (PRSS) is very rare, accounting for approximately 1% of synovial sarcomas. It is a spindle cell tumor type affecting mesenchymal tissue, and has morphological, genetic, and clinical characteristics, and a certain degree of epithelial differentiation. It is highly malignant and has the fourth highest incidence among soft tissue sarcomas. Here, we report a case of PRSS and share some valuable information about the disease. CASE SUMMARY: A 54-year-old male patient was admitted to the hospital for a space-occupying lesion in the right kidney for 2 d upon ultrasound examination. The patient had no cold or fever; no frequency, urgency or pain of urination; and no other discomfort. The results of a hemogram, blood biochemistry, and tumor markers were in the normal range. The patient was examined by computed tomography (CT), which indicated the presence of a soft tissue density shadow with a diameter of approximately 6.8 cm in the right renal pelvis area, showing uneven enhancement. Ultrasound indicated a cystic solid mass of approximately 6.8 cm × 6.5 cm in the right kidney, with an unclear boundary and irregular shape. Meanwhile, color Doppler flow imaging showed dotted blood flow signals in the periphery and interior. Contrast-enhanced ultrasound (CEUS) showed "slow in and fast out" hyperenhancement of the right renal mass after contrast agent injection. The postoperative pathological diagnosis was (right kidney) synovial sarcoma. Despite postoperative adjuvant chemotherapy, tumor recurrence was detected two years later. CONCLUSION: PRSS is a rare malignant tumor. To date, no characteristic imaging findings have been observed. The diagnosis is confirmed primarily through postoperative pathological immunohistochemistry and SS18 (SYT) gene detection. In this case, CEUS was used preoperatively. We found that PRSS has the characteristic of "slow in and fast out" hyperenhancement, and its particular characteristics have diagnostic value. Postoperative adjuvant chemotherapy is not very effective.

Suppression of c­FLIPL promotes JNK activation in malignant melanoma cells.

The up­regulation of cellular Fas­associated death domain­like interleukin­1ß­converting enzyme (FLICE)­like inhibitory protein (c­FLIP) has been reported in various tumor types, and has been previously shown to be associated with the clinicopathological features of melanoma. To assess its potential role in cancer therapy, the present study evaluated the effects of short hairpin (sh)RNAs of different c­FLIP isoforms on cellular proliferation and c­Jun N­terminal kinase (JNK) signaling. Human c­FLIP shRNA plasmids were constructed and transfected into the A875 melanoma cell line. It was observed that c­FLIP shRNA exhibited strong inhibitory effects against the levels of phosphorylated­JNK and inhibited cellular proliferation in A875 cells. Thus, this indicated that c­FLIP long form shRNA serves a specific inhibitory role in cellular proliferation through inducing the activation of the JNK pathway in A875 cells. The present study provided insight into the development of RNAi based therapies for melanoma.

Weaving of organic threads into a crystalline covalent organic framework.

A three-dimensional covalent organic framework (COF-505) constructed from helical organic threads, designed to be mutually weaving at regular intervals, has been synthesized by imine condensation reactions of aldehyde functionalized copper(I)-bisphenanthroline tetrafluoroborate, Cu(PDB)2(BF4), and benzidine (BZ). The copper centers are topologically independent of the weaving within the COF structure and serve as templates for bringing the threads into a woven pattern rather than the more commonly observed parallel arrangement. The copper(I) ions can be reversibly removed and added without loss of the COF structure, for which a tenfold increase in elasticity accompanies its demetalation. The threads in COF-505 have many degrees of freedom for enormous deviations to take place between them, throughout the material, without undoing the weaving of the overall structure.

Synthesis of 5'-O-DMT-2'-O-TBS Mononucleosides Using an Organic Catalyst.

This unit describes a highly effective method to produce 5'-O-DMT-2'-O-TBS mononucleosides selectively using a small organic catalyst. This methodology avoids the tedious protection/deprotection strategy necessary to differentiate the 2'- and 3'-hydroxyl groups in a ribonucleoside. The catalyst was synthesized in two steps, starting from the condensation of valinol and cyclopentyl aldehyde, followed by anionic addition of N-methylimidazole. Ring closure of the amino alcohol with N,N-dimethylformamide dimethyl acetal in methanol furnishes the catalyst. All four 2'-O-TBS protected mono-nucleosides, U, A(Bz), G(Ib), and C(Ac), were produced in a single step using 10 to 20 mol% of the catalyst at room temperature with excellent yields and selectivity. Further transformation to phosphoramidite demonstrates the utility of this protocol in the preparation of monomers useful for automated synthesis of RNA.

Resolution of terminal 1,2-diols via silyl transfer.

Through kinetic analysis and optimization, we report an improved resolution of terminal 1,2-diols via asymmetric silyl transfer. Because the reaction is a regiodivergent resolution, the monoprotected product could be isolated in excess of 95:5 er and 40% yield. The described method offers a means of chemically differentiating a terminal 1,2-diol with concomitant resolution of the enantiomers.

Practical silyl protection of ribonucleosides.

Herein we report the site-selective silylation of the ribonucelosides. The method enables a simple and efficient procedure for accessing suitably protected monomers for automated RNA synthesis. Switching to the opposite enantiomer of the catalyst allows for the selective silylation of the 3'-hydroxyl, which could be used in the synthesis of unnatural RNA or for the analoging of ribonucelosides. Lastly, the procedure was extended to ribavirin a potent antiviral therapeutic.