Genetic and prognostic analysis of blastoid and pleomorphic mantle cell lymphoma: a multicenter analysis in China.

Blastoid or pleomorphic mantle cell lymphoma (B/P-MCL) is characterized by high invasiveness and unfavorable outcomes, which is still a challenge for treating MCL. This retrospective study was performed to comprehensively analyze the clinical, genomic characteristics and treatment options of patients with B/PMCL from multicenter in China. Data were obtained from 693 patients with B/PMCL from three centers in China between April 1999 and December 2019. Seventy-four patients with BMCL (n = 43) or PMCL (n = 31) were included in the analysis. The median age of the cohort was 60.0 years with a male-to-female ratio of 2.89:1. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 44.1% and 46.0%, respectively. Mutations of TP53, ATM, NOTCH1, NOTCH2, NSD2, SMARCA4, CREBBP, KMT2D, FAT1, and TRAF2 genes were the most common genetic changes in B/P-MCL. Progression of disease within 12 months (POD12) could independently predict the poor prognosis of patients with blastoid and pleomorphic variants. Patients with POD12 carried a distinct mutation profile (TP53, SMARCA4, NSD2, NOTCH2, KMT2D, PTPRD, CREBBP, and CDKN2A mutations) compared to patients with non-POD12. First-line high-dose cytosine arabinoside exposure obtained survival benefits in these populations, and BTKi combination therapy as the front-line treatment had somewhat improvement in survival with no significant difference in the statistic. In conclusion, B/P-MCL had inferior outcomes and a distinct genomic profile. Patients with POD12 displayed a distinct mutation profile and a poor prognosis. New therapeutic drugs and clinical trials for B/P-MCL need to be further explored.

CXCL12/CXCR4 facilitates perineural invasion via induction of the Twist/S100A4 axis in salivary adenoid cystic carcinoma.

The activation of CXCL12/CXCR4 axis participated in the progression of multiple cancers, but potential effect in terms of perineural invasion (PNI) in SACC remained ambiguous. In this study, we identified that CXCL12 substantially expressed in nerve cells. CXCR4 strikingly expressed in tumour cells, and CXCR4 expression was closely associated with the level of EMT-associated proteins and Schwann cell hallmarks at nerve invasion frontier in SACC. Activation of CXCL12/CXCR4 axis could promote PNI and up-regulate relative genes of EMT and Schwann cell hallmarks both in vitro and in vivo, which could be inhibited by Twist silence. After overexpressing S100A4, the impaired PNI ability of SACC cells induced by Twist knockdown was significantly reversed, and pseudo foot was visualized frequently. Collectively, the results indicated that CXCL12/CXCR4 might promote PNI by provoking the tumour cell to differentiate towards Schwann-like cell through Twist/S100A4 axis in SACC.

Fibroblasts in cancer dormancy: foe or friend?

Cancer dormancy is defined that the residual cancer cells could enter into a state of quiescence and patients remain asymptomatic for years or even decades after anti-tumor therapies. Fibroblasts, which represent a predominant cell type in tumor microenvironment, play a pivotal role in determining the ultimate fate of tumor cells. This review recapitulates the pleiotropic roles of fibroblasts which are divided into normal, senescent, cancer-associated fibroblasts (CAFs) and circulation CAFs in tumor dormancy, relapse, metastasis and resistance to therapy to help the treatment of cancer metastasis.

Fatty acid synthase contributes to epithelial-mesenchymal transition and invasion of salivary adenoid cystic carcinoma through PRRX1/Wnt/ß-catenin pathway.

Fatty acid synthase (FASN) has been shown to be selectively up-regulated in cancer cells to drive the development of cancer. However, the role and associated mechanism of FASN in regulating the malignant progression of salivary adenoid cystic carcinoma (SACC) still remains unclear. In this study, we demonstrated that FASN inhibition attenuated invasion, metastasis and EMT of SACC cells as well as the expression ofPRRX1, ZEB1, Twist, Slug and Snail, among which the level of PRRX1 changed the most obviously. Overexpression of PRRX1 restored migration and invasion in FASN knockdown cells, indicating that PRRX1 is an important downstream target of FASN signalling. Levels of cyclin D1 and c-Myc, targets of Wnt/ß-catenin pathway, were significantly decreased by FASN silencing and restored by PRRX1 overexpression. In addition, FASN expression was positively associated with metastasis and poor prognosis of SACC patients as well as with the expression of PRRX1, cyclin D1 and c-Myc in SACC tissues. Our findings revealed that FASN in SACC progression may induce EMT in a PRRX1/Wnt/ß-catenin dependent manner.

Extracellular vesicle long non-coding RNA-mediated crosstalk in the tumor microenvironment: Tiny molecules, huge roles.

Emerging evidence has shown that dynamic crosstalk among cells in the tumor microenvironment modulates the progression and chemotherapeutic responses of cancer. Extracellular vesicles comprise a crucial form of intracellular communication through horizontal transfer of bioactive molecules, including long non-coding RNA (lncRNA), to neighboring cells. Three main types of extracellular vesicles are exosomes, microvesicles and apoptotic bodies, exhibiting a wide range of sizes and different biogenesis. Over the last decade, dysregulation of extracellular vesicle lncRNA has been revealed to remodel the tumor microenvironment and induce aggressive phenotypes of tumor cells, thereby facilitating tumor growth and development. This review will focus on extracellular vesicle lncRNA-mediated crosstalk between tumor cells and recipient cells, including tumor cells as well as stromal cells in the tumor microenvironment, and overview the mechanisms by which lncRNA are selectively sorted into extracellular vesicles, which may pave the way for their clinical application in cancer diagnosis and treatment.

Who is who in oral cancer?

Great attention has been attached to explore the association between oral bacteria and oral cancer. Recently, four common inhabitants of oral cavity, Porphyromonas gingivalis, Fusobacterium nucleatum, Treponema denticola and Streptococcus anginosus, have been identified as potential etiologic bacterial agents for oral carcinogenesis. They might promote the oncogenesis and progression of oral cancer by induction of chronic inflammation, enhancement of migration and invasiveness, inhibition of cell apoptosis, augment of cell proliferation, suppression of immune system and production of carcinogenic substances. Thus, this review will focus on the possible mechanisms of these oral bacteria contributing to occurrence and development of oral cancer, and the potential clinical implications of utilizing oral bacteria on the diagnosis, prevention and treatment of oral cancer will be discussed.

Ba10In6Zn7S26- nZnS: An Inorganic Composite System with Interface Phase-Matching Tuned for High-Performance Infrared Nonlinear Optical Materials.

Mid- and far-infrared nonlinear optical (MFIR NLO) materials are important in modern laser technologies. However, it is very challenging to develop materials that can achieve a subtle balance between the key requirements, such as large NLO response, high laser-induced damage threshold (LIDT), wide IR transparency, and phase-matching. In this work, a new wide IR transparency (0.38-15.3 µm) NLO crystal Ba10In6Zn7S26 (SS26) is synthesized. Further, its composite system Ba10In6Zn7S26- nZnS is synthesized by eutectic reaction. In particular, Ba10In6Zn7S26-14ZnS (SS40) shows excellent balanced NLO performance that includes a large band gap of 3.05 eV, high LIDT (13.3 × AgGaS2), large second harmonic generation (SHG) response (2.1 × AgGaS2 at 2050 nm, 5.2 × KDP at 1064 nm), and wide optical transmission window (0.37-15.4 µm). Importantly, the phase-matching condition is realized for SS40 by interfaces formed between the crystal face (112) of matrix SS26 and the crystal face (111) of reinforcement cubic ZnS by topological chemical reaction, and the NLO performance can be tuned by different concentrations of ZnS. First-principles simulations are employed to study NLO properties of SS26 and the interfaces. This work demonstrates that SS40 is a promising MFIR NLO material, and tuning components of the composite material system is a useful way to develop new MFIR NLO materials with excellent comprehensive performance.

Specific phosphorylation of histone demethylase KDM3A determines target gene expression in response to heat shock.

Histone lysine (K) residues, which are modified by methyl- and acetyl-transferases, diversely regulate RNA synthesis. Unlike the ubiquitously activating effect of histone K acetylation, the effects of histone K methylation vary with the number of methyl groups added and with the position of these groups in the histone tails. Histone K demethylases (KDMs) counteract the activity of methyl-transferases and remove methyl group(s) from specific K residues in histones. KDM3A (also known as JHDM2A or JMJD1A) is an H3K9me2/1 demethylase. KDM3A performs diverse functions via the regulation of its associated genes, which are involved in spermatogenesis, metabolism, and cell differentiation. However, the mechanism by which the activity of KDM3A is regulated is largely unknown. Here, we demonstrated that mitogen- and stress-activated protein kinase 1 (MSK1) specifically phosphorylates KDM3A at Ser264 (p-KDM3A), which is enriched in the regulatory regions of gene loci in the human genome. p-KDM3A directly interacts with and is recruited by the transcription factor Stat1 to activate p-KDM3A target genes under heat shock conditions. The demethylation of H3K9me2 at the Stat1 binding site specifically depends on the co-expression of p-KDM3A in the heat-shocked cells. In contrast to heat shock, IFN-γ treatment does not phosphorylate KDM3A via MSK1, thereby abrogating its downstream effects. To our knowledge, this is the first evidence that a KDM can be modified via phosphorylation to determine its specific binding to target genes in response to thermal stress.

Identification of serum microRNAs as diagnostic and prognostic biomarkers for acute pancreatitis.

BACKGROUND/OBJECTIVES: To identify serum microRNA (miRNA) as diagnostic and prognostic biomarkers for acute pancreatitis (AP). MATERIALS AND METHODS: Sera microRNA expression was profiled from 12 AP patients with varying disease severity and three healthy controls. Differentially expressed miRNAs were validated in a larger cohort of patients and controls. The diagnostic and prognostic potentials of differentially expressed miRNAs were evaluated using receiver operating characteristic (ROC) curve analysis and compared to that of classic prognostic markers for AP. RESULTS: miRNA microarray analyses identified 205 differentially expressed miRNAs between sera from AP patients and that from controls. Nine miRNAs were differentially expressed between severe and mild AP patients. Further validation confirmed the down-regulation of miR-92b, miR-10a, and miR-7 in AP patients, and ROC analysis revealed that these miRNAs can differentiate AP from health cases. Furthermore, the serum miR-551b-5p level was significantly higher in patients with disease complications or a low plasma calcium level. ROC analysis showed that the serum miR-551b-5p level can distinguish between severe and mild AP. CONCLUSION: The expressions of miR-92b, miR-10a, and miR-7 in AP might be used for the early diagnosis of AP and miR-551b-5p may be used for predicting AP severity.

Syntheses, characterization, and optical properties of ternary Ba-Sn-S system compounds: acentric Ba7Sn5S15, centric BaSn2S5, and centric Ba6Sn7S20.

Three new ternary Ba-Sn-S system compounds, acentric Ba(7)Sn(5)S(15), centric BaSn(2)S(5), and centric Ba(6)Sn(7)S(20) have been designed and synthesized by a conventional high-temperature solid-state reaction method using the evacuated silica tubes. The crystal structure of Ba(7)Sn(5)S(15) shows the coexistence of a SnS(4) tetrahedral and a Sn(2)S(3) trigonal bipyramid. Importantly, the larger dipole moment of the [Sn(2)S(3)](2-) trigonal bipyramid group and the polarity enhancement of the bipyramidal arrangements result in a strong SHG effect at 2.05 µm, which is 10 times of the SHG intensity of the benchmark AgGaS(2) with the particle size of 30-46 µm and twice as much as that with the particle size of 150-212 µm. Evidently, the acentric Ba(7)Sn(5)S(15) is a novel IR NLO crystal material with a wide mid-IR window and a strong SHG effect, which is the first reported among the Ba-Sn-S ternary system. Moreover, Ba(7)Sn(5)S(15) can achieve type-I phase-matching that can be used for practical applications. In the centric BaSn(2)S(5,) all Sn atoms are coordinated by five S atoms to form novel SnS(5) trigonal bipyramid polyhedrons. In the other centric Ba(6)Sn(7)S(20), there is the coexistence of the two coordination patterns with a SnS(5) trigonal bipyramid and SnS(4) tetrahedral polyhedrons, featuring a special crystal structure in the Ba-Sn-S system.

[Sterol regulatory element binding protein 1 and its target gene networks].

Sterol regulatory element binding protein 1 (SREBP-1) is one of the important nuclear transcription factors. SREBP-1 can maintain lipids dynamic equilibrium by regulating the expression of enzymes required for synthesis of endogenous cholesterol, fatty acids, triglycerides and phospholipids. Anomalies of SREBP-1 and its target genes can cause a series of metabolic diseases such as insulin resistance, type Ⅱ diabetes, heart dysfunction, vascular complications and hepatic steatosis. In these years, the development of high-throughput technologies has greatly expanded our knowledge about SREBP-1 target genes and the pattern of transcriptional regulation. Here we reviewed recent research progress of SREBP-1, with a focus on the protein structure, activation process, DNA binding sites and target genes. Most importantly, we showed the transcriptional regulatory networks based on omics datasets, which will contribute to a better understanding of the role of SREBP-1 in lipid metabolism and provide new clues for the treatment of lipid metabolism disorders.

Mechanical behavior and reloading reinforcement characteristics of fractured coal under low confining pressure.

To study the basic mechanical behavior and the reloading reinforcement characteristics of fractured coal, conventional triaxial loading tests with different fissure angle were first carried out. On this basis, conventional triaxial loading and unloading tests were conducted to investigate the reloading reinforcement characteristics of fractured coal. The results reveal that when the fissure angle was small, the stress-strain curve exhibited the multi-peak phenomena. As the fissure angle increased, the stress drop phenomenon in the peak region was weakened. With the increase of the fissure angle, the peak stress of the specimens increased and then decreased, while the elastic modulus showed an overall increasing trend, demonstrating the controlling effect of the crack angle. Meanwhile, the cyclic loading exhibited a certain enhancement effect on the strength of the fractured coals when the specimens was unloaded near the crack closure stress. The findings can provide a better understanding of the failure mechanism and reloading reinforcement characteristics of fractured coal.

Syntheses and magnetic properties study of isostructural BiM2BP2O10 (M = Co, Ni) containing a quasi-1D linear chain structure.

We present here the structures and magnetism of two quasi-1D linear chain compounds of BiM(2)BP(2)O(10) (M = Co, Ni), which were synthesized by traditional solid-state reactions for the first time. Two title compounds crystallize in the monoclinic system with space group P2(1)/c and feature novel 3D structures with a linear chain structure of {MO(6)}(n) further connected by [BP(2)O(10)](7-) anionic groups. The results of magnetic property measurements evidence the antiferromagnetic properties of both compounds in low magnetic field and a field-dependent metamagnetic transition from the antiferromagnetic to ferromagnetic ground state of the BiCo(2)BP(2)O(10) complex.

Syntheses, crystal and electronic structures, and characterizations of quaternary antiferromagnetic sulfides: Ba2MFeS5 (M = Sb, Bi).

Two new quaternary sulfides, Ba(2)SbFeS(5) and Ba(2)BiFeS(5), were synthesized by using a conventional high-temperature solid-state reaction method in closed silica tubes at 1123 K. The two compounds both crystallize in the orthorhombic space group Pnma with a = 12.128(6) Å, b = 8.852(4) Å, c = 8.917(4) Å, and Z = 4 for Ba(2)SbFeS(5) and a = 12.121(5) Å, b = 8.913(4) Å, c = 8.837(4) Å, and Z = 4 for Ba(2)BiFeS(5). The crystal structure unit can be viewed as an infinite one-dimensional edge-shared MS(5) (M = Sb, Bi) tetragonal-pyramid chain with FeS(4) tetrahedra alternately arranged on two sides of the MS(5) polyhedral chain via edge-sharing (so the chain can also be written as (1)(∞)[MFeS(5)](4-)). Interestingly, the compounds have the structural type of a Ba(3)FeS(5) high-pressure phase considering one Ba(2+) is replaced by one Sb(3+)/Bi(3+), with Fe(4+) reduced to Fe(3+) for in order to maintain the electroneutrality of the system. As a result, the isolated iron ions in Ba(3)FeS(5) are bridged by intermediate MS polyhedra in Ba(2)MFeS(5) (M = Sb, Bi) compounds and form the (1)(∞)[MFeS(5)](4-) chain structure. This atom substitution of Ba(2+) by one Sb(3+)/Bi(3+) leads to a magnetic transition from paramagnetic Ba(3)FeS(5) to antiferromagnetic Ba(2)MFeS(5), resulting from an electron-exchange interaction of the iron ions between inter- or intrachains. Magnetic property measurements indicate that the two compounds are both antiferromagnetic materials with Néel temperatures of 13 and 35 K for Ba(2)SbFeS(5) and Ba(2)BiFeS(5), respectively. First-principles electronic structure calculations based on density functional theory show that the two compounds are both indirect-band semiconductors with band gaps of 0.93 and 1.22 eV for Ba(2)SbFeS(5) and Ba(2)BiFeS(5), respectively.

Syntheses and characterization of new mid-infrared transparency compounds: centric Ba2BiGaS5 and acentric Ba2BiInS5.

Two new mid-infrared transparency compounds, centric Ba(2)BiGaS(5) (1) and acentric Ba(2)BiInS(5) (2), were synthesized from a high-temperature solid-state reaction in evacuated closed silica tubes. Their crystal structures were determined by a single crystal X-ray diffraction method at 293 K. The results of crystal structure solution indicate that compound 1 crystallizes in the centrosymmetric space group Pnma with trans- (1)(∞)[BiGaS(5)](4-) chain structure, while compound 2 crystallizes in the noncentrosymmetric polar space group Cmc2(1) with cis- (1)(∞)[BiInS(5)](4-) chain structure. Two types of lone-pair electrons alignment fashions within (1)(∞)[BiMS(5)](4-) chains result in destructive (for 1) or constructive (for 2) dipole moments, as illustrated in the crystal structures and the partial electron density maps based on the first-principles electronic structure computations. Powder second-harmonic generation (SHG) experiments with a 2.05 µm pumping laser show that the SHG efficiency of the polar compound 2 is approximately 0.8 times that of KTiOPO(4) (KTP) reference. Furthermore, SHG signal intensity measurements using different size particles of powder samples indicate that compound 2 can also achieve type I phase-matching, which makes the compound promising for practical applications.

Inhibition of DEC2 is necessary for exiting cell dormancy in salivary adenoid cystic carcinoma.

BACKGROUND: Patients were prone to have poor prognosis once dormant tumor cells being reactivated. However, the molecular mechanism of tumor cell dormancy remains poorly understood. This study aimed to investigate the function of DEC2 in the dormancy of salivary adenoid cystic carcinoma (SACC) in vitro and vivo. METHODS: The function of DEC2 in tumor dormancy of SACC was investigated in nude mice by establishing primary and lung metastasis model. Meanwhile, the interaction between hypoxia and SACC dormancy and the role of DEC2 were demonstrated through CoCl2 induced hypoxia-mimicking microenvironments. Furthermore, the expression of DEC2 was detected by immunohistochemical staining in primary SACC samples with and without recurrence. RESULTS: In the primary SACC, DEC2 overexpression inhibited cell proliferation, increased cell population arrested in G0/G1 phase, and participated in dormancy regulation, which limited tumor growth. Intriguingly, in the model of lung metastasis, the level of DEC2 was reduced significantly and resulted in dormancy exit and growth resumption of SACC cells. Then, we found that DEC2 may associate with hypoxia in contributing to tumor dormancy, which might provide a possible cue to explain the different roles of DEC2 in primary and metastasis lesions. And overexpression of DEC2 induced dormancy and promoted migration and invasion through activating EMT program. Finally, DEC2 positive expression was shown to be significantly correlated with recurrence and dormancy of SACC patients. CONCLUSIONS: These findings provide a novel insight into the role of DEC2 gene in tumor dormancy and metastasis.

5-Hydroxymethylcytosine profiles of cfDNA are highly predictive of R-CHOP treatment response in diffuse large B cell lymphoma patients.

BACKGROUND: Although R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) remains the standard chemotherapy regimen for diffuse large B cell lymphoma (DLBCL) patients, not all patients are responsive to the scheme, and there is no effective method to predict treatment response. METHODS: We utilized 5hmC-Seal to generate genome-wide 5hmC profiles in plasma cell-free DNA (cfDNA) from 86 DLBCL patients before they received R-CHOP chemotherapy. To investigate the correlation between 5hmC modifications and curative effectiveness, we separated patients into training (n = 56) and validation (n = 30) cohorts and developed a 5hmC-based logistic regression model from the training cohort to predict the treatment response in the validation cohort. RESULTS: In this study, we identified thirteen 5hmC markers associated with treatment response. The prediction performance of the logistic regression model, achieving 0.82 sensitivity and 0.75 specificity (AUC = 0.78), was superior to existing clinical indicators, such as LDH and stage. CONCLUSIONS: Our findings suggest that the 5hmC modifications in cfDNA at the time before R-CHOP treatment are associated with treatment response and that 5hmC-Seal may potentially serve as a clinical-applicable, minimally invasive approach to predict R-CHOP treatment response for DLBCL patients.

A strong second-harmonic generation material Cd4BiO(BO3)3 originating from 3-chromophore asymmetric structures.

In this communication, the novel nonlinear optical crystal material Cd(4)BiO(BO(3))(3) with 3-chromophore asymmetric structures of CdO(n), BiO(6), and BO(3) groups has been prepared by a flux method, and the single crystal structure has been determined with the space group Cm. It is the largest NLO coefficient for Cd(4)BiO(BO(3))(3) among borate systems, and the strong NLO response originates from cooperation effects of the 3-chromophore asymmetric structures composed of the polar displacement of d(10) Cd(2+) ion, stereochemically active lone pair of Bi(3+), and pi-delocalization of BO(3). These evidence are provided in view of evaluations of calculated density of states and electron-density difference maps. The experimental measurements show that the features of a large SHG effect, phase-match, and high thermal stability will be favorable in industrial production and applications for Cd(4)BiO(BO(3))(3).

BaM(BS(3))S (M = Sb, Bi): two new thioborate compounds with one-dimensional polymeric chain structure.

Two new quaternary thioborate compounds with strongly one-dimensional growth, BaSb(BS(3))S and BaBi(BS(3))S, have been synthesized using the conventional solid state reaction method in closed tubes at 1100 K. The single crystal X-ray diffraction analysis has shown that compound BaSb(BS(3))S crystallizes in space group Pnma of the orthorhombic system with unit cell parameters of a = 9.6898(15) A, b = 6.2293(13) A, c = 11.670(2) A, V = 704.4(2) A(3), and Z = 4, while compound BaBi(BS(3))S crystallizes in space group C2/m with unit cell parameters of a = 14.9890(17) A, b = 6.2457(6) A, c = 7.5591(9) A, beta = 101.604(5) degrees , V = 693.19(13) A(3), and Z = 4. The two compounds both crystallize in the structure of infinite one-dimensional chains with [BS(3)](3-) trigonal plane coordination alternately bridged by [MS(3)](3-) (M = Sb, Bi) trigonal pyramids through sharing two sulfur atoms along the crystallographic b axis. First-principles electronic structure calculations performed with the density functional theory (DFT) method show that the calculated band gaps of BaSb(BS(3))S and BaBi(BS(3))S are 2.29 and 2.16 eV, respectively, which are in good agreement with the experimental values estimated from UV-vis absorption spectra using the Kubelka-Munk equation, and the observed absorption peak is assigned as charge transfers from S-3p states to Sb-5p (Bi6p) states.

Light stimulus responsive nanomedicine in the treatment of oral squamous cell carcinoma.

Light stimulus responsive therapies are based on a variety of low-toxic therapeutic agents and produce anti-tumor effects only under external light stimulation, thus greatly reducing system toxicity and improving the specificity of treatment. Moreover, light stimulus responsive drug delivery system (DDS) can combine various theranostics molecules to exert synergistic therapeutic effects of various treatments, which has played an important role in cancer treatment. In this review, we introduced the light stimulus responsive cancer therapies including photodynamic therapy (PDT), photothermal therapy (PTT) and light-triggered DDS applied in the treatment of OSCC, described considerable photosensitizers (PSs) and nanomaterials used for oral cancers, which will hope to better the clinic outcome of OSCC patients.