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Purpose: Cluster I pheochromocytomas and paragangliomas (PCPGs) tend to develop malignant transformation, tumor recurrence, and multiplicity. Transcriptomic profiling suggests that cluster I PCPGs and other related tumors exhibit distinctive changes in the tricarboxylic acid (TCA) cycle, the hypoxia signaling pathway, mitochondrial electron transport chain, and methylation status, suggesting that therapeutic regimen might be optimized by targeting these signature molecular pathways.Experimental Design: In the present study, we investigated the molecular signatures in clinical specimens from cluster I PCPGs in comparison with cluster II PCPGs that are related to kinase signaling and often present as benign tumors.Results: We found that cluster I PCPGs develop a dependency to mitochondrial complex I, evidenced by the upregulation of complex I components and enhanced NADH dehydrogenation. Alteration in mitochondrial function resulted in strengthened NAD+ metabolism, here considered as a key mechanism of chemoresistance, particularly, of succinate dehydrogenase subunit B (SDHB)-mutated cluster I PCPGs via the PARP1/BER DNA repair pathway. Combining a PARP inhibitor with temozolomide, a conventional chemotherapeutic agent, not only improved cytotoxicity but also reduced metastatic lesions, with prolonged overall survival of mice with SDHB knockdown PCPG allograft.Conclusions: In summary, our findings provide novel insights into an effective strategy for targeting cluster I PCPGs, especially those with SDHB mutations. Clin Cancer Res; 24(14); 3423–32. ©2018 AACR.

Supplementary Figures S1 A. Quantitative PCR showed CA9, PNMT, and VEGFA expression in MTT cells. Higher expressions of hypoxia related genes were detected in SDHBKD cells. B. NAD+ quantification confirmed depletion of NAD+ by Nampt inhibitors FK866 and CHS828. C. Blue native gel analysis on mitochondrial complex formation in MTT cells (left panel). Mitochondrial complex I formation is increased in SDHBKD cells. In gel enzyme activity assay (IGA) showed elevated mitochondrial complex I activity in SDHBKD cells (right panel). D. Re-expression of SDHB in MTT cells (upper panel). The re-expression of SDHB reduced pADPR formation in SDHBKD cells, with a corresponding increased of γH2A.X expression (lower panel). E. Quantification of NAD+/NADH ratio in MTT cells. Re-expression of SDHB partially reversed the elevated NAD+/NADH ratio in SDHBKD cells. F. Quantification of flow cytometry data. A significant G2/M arrest is seen in combination treated group. G. Western blot for MGMT detection in MTT cells. No MGMT expression was seen in either SDHBWT or SDHBKD cells.ï€ ï�¢-actin was used as loading control. H. Cell viability test showing enhanced cytotoxic effect of combination treatment. **p

Green merger and acquisition (GMA) is becoming a growing tendency for heavily polluting enterprises in recent years; however, the realization path of green transformation through GMA is still unexplored. Taking 48 Chinese heavily polluting enterprises that had GMA in 2018 as the research object, this paper constructs the "MA attributes, Organizational characteristics, and External environment" (M-O-E) framework, by using the method of fuzzy-set qualitative comparative analysis (fsQCA) to reveal the configurations of conditions that lead to high levels of green innovation performance. The results show that the high green technology innovation performance after GMA of heavily polluting enterprises is the outcome of multiple antecedents, and no singular antecedent is sufficient for achieving it. Besides, there are three equivalent configurations of conditions to achieve green transformation: professional buyer, internal leading, and internal-external linkage. Among them, the professional buyer configuration highlights that the combination of MA experience and MA scale is of great importance, the internal leading configuration emphasizes that the existence of environmental awareness and organizational resources is the core conditions, and the internal-external linkage configuration requires simultaneous efforts of MA experience and government environmental regulations. Our research contributes to the understanding of green transformation in heavily polluting enterprises from a configurational perspective, and provides a practice-oriented guide to achieve green transformation for the government and heavily polluting enterprises.

Purpose: Acupuncture treatment of rheumatoid arthritis (RA) has a long history and has been widely recognized in the medical community. However, its mechanism of action still is rarely uncovered. In the present study, the effects of acupuncture on the immune function and MAPK pathway in synovial tissue of rats with RA were investigated; it aimed to explore the effect and mechanism of acupuncture on alleviating RA. Methods: Rats were randomly divided into control, model and acupuncture groups, 15 rats each group, and RA rat model was induced via bovine type II collagen in complete Freund's adjuvant. The acupuncture group received "Zusanli" and "Shenshu" warm acupuncture treatment on the first day after modeling, acupuncture stimulation once a day for 21 days. The rat weight and degree of joint swelling were recorded and calculated. The ankle joint histopathology was observed by H&E staining. Serum inflammatory cytokines were detected using ELISA. An automatic biochemical analyzer was used to test serum IgG, IgM and IgA levels. Transcription factors T-bet, GATA3, RORγT, Foxp3 mRNA were monitored through RT-qPCR technology. Further, the expression of key targets of MAPK signal or phosphorylation in synovial tissue were determined using Western blotting. Results: Acupuncture relieved the joint swelling and weight loss of RA rats, ameliorated the pathological damage of the ankle joint, significantly increased the serum IgG, IgM, IgA and T-bet, and Foxp3 levels, and reduced the levels of IL-1β, IL-6, TNF-α, GATA3, and RORγT; down-regulated synovial tissue p-p38MAPK, p-JNK, and p-ERK1/2 levels and protein phosphorylation ratio (P Conclusion: Acupuncture stimulation can improve the joint damage and promote the immune function of RA rats, possibly via blocking the expression of MAPK pathway in synovial tissue. This study provides a scientific and promising reference for acupuncture further in the clinical strategy of RA.

Purpose Meningiomas are common primary central nervous system tumors. Although complete surgical resection is still the main therapeutic strategy, gene phenotypes, DNA methylation and chromosome copy number variations (CNVs) are also key factors in prognostication and growth rate prediction. In this study, we evaluated the relationship between growth rate and specific gene mutations, DNA methylation and CNVs to provide a reference for surgeons and establish individual treatment strategies. Method From Jan 2020 to Sept 2021, 50 meningioma patients underwent surgical resection. According to our criteria, 26 patients belonged to the fast growth (FG) group, in which the growth rate was over 4 mm/year. The other 24 patients belonged to the slow growth (SG) group, in which the growth rate was slower than 2 mm/year. Genomic DNA samples from fresh tumor tissue were collected, and gene mutations, DNA methylation and chromosome CNVs were also analyzed separately. Result Different age and grade distributions were found between FG group and SG group. The mutation rates of LGI1, YEATS4 and BRAF were significantly higher in the FG group than in the SG group. The mutation rates of other genes were found descriptively different between the FG group than in the SG group. In addition, descriptively differences in DNA methylation and the rate of CNVs were found between the FG and SG groups. Conclusion Gene phenotypes, DNA methylation and CNVs can be used to predict the growth rate of meningioma, which has a higher power for predicting tumor biological characteristics than the WHO classification in meningiomas. These findings will aid surgeons in setting up individual treatment strategies.

A [Formula: see text]-ring [Formula: see text] is called a nil [Formula: see text]-clean ring if every element of [Formula: see text] is a sum of a projection and a nilpotent. Nil [Formula: see text]-clean rings are the [Formula: see text]-version of nil-clean rings introduced by Diesl. This paper is about the nil [Formula: see text]-clean property of rings with emphasis on matrix rings. We show that a [Formula: see text]-ring [Formula: see text] is nil [Formula: see text]-clean if and only if [Formula: see text] is nil and [Formula: see text] is nil [Formula: see text]-clean. For a 2-primal [Formula: see text]-ring [Formula: see text], with the induced involution given by[Formula: see text], the nil [Formula: see text]-clean property of [Formula: see text] is completely reduced to that of [Formula: see text]. Consequently, [Formula: see text] is not a nil [Formula: see text]-clean ring for [Formula: see text], and [Formula: see text] is a nil [Formula: see text]-clean ring if and only if [Formula: see text] is nil, [Formula: see text]is a Boolean ring and [Formula: see text] for all [Formula: see text].

Let R be a commutative ring, m>1 an integer and q>1 an odd number. The following questions are addressed: (1) when is every element in Mn(R) and, respectively, in Tn(R) a product of q-potents? (2) ...

A nonzero sum of a unit and a nilpotent element in a ring is called a fine element. This is a study of rings in which every nonzero nilpotent is fine, which we call NF rings.

An element a in a ring R is left uniquely generated (or left UG) if, whenever Ra = Rb, a = ub for a unit u in R, and is left strongly UG if, whenever Ra = Rb, a = ub = bu for a unit u in R. A ring ...

The distribution and ecological risks of 11 phenolic compounds were studied in Weihe River, Northwest China. The concentrations of phenolic compounds were determined by ultra-high performance liquid chromatography (UPLC). The total concentration of 11 phenolic compounds (∑PC11) ranged from 0.06 to 14.12 μg/L with an average of 5.22 μg/L in water, from 0.92 to 34,885 μg/g with an average of 4,446 μg/g in suspended particulate matter (SPM), and from 3.54 to 34.09 μg/g with an average of 11.09 μg/g in sediment. For individual phenolic compound, the mean concentration of pentachlorophenol was the highest in water (2.65 μg/L) and in SPM (3,865 μg/g), while in sediment the mean concentration of 2,4,6-trichlorophenol was the highest (3.05 μg/g). The total concentration of 5 chlorophenols (∑CP5) was significantly higher than that of 6 non-chlorophenols (∑NCP6) in all three studied compartments. The phenolic compounds in Weihe River were at moderate levels in water and at high levels in sediment. The ecological risk assessment results indicated that phenolic compounds exhibited a high ecological risk in Weihe River water. In most sites, the distribution coefficient (Kd) (SPM) was much higher than Kd (sediment), which probably suggested fresh phenolic compounds input in Weihe River. HIGHLIGHTS This is the first systematic study of phenolic compounds in rivers in northwest China.; The results of ecological risk assessment indicated that phenolic compounds exhibited a high ecological risk in Weihe River water.; The total concentration of 5 chlorophenols (∑CP5) was significantly higher than that of 6 non-chlorophenols (∑NCP6) both in water and sediment.

The goal of this note is to completely determine the rings for which every nonunit is a product of a nilpotent and an idempotent (in either order).

We give the necessary and sufficient conditions for an n × n matrix over an integral domain to be a sum of involutions and, respectively, a sum of tripotents. We determine the integral domains over...

A ring is said to satisfy the strong 2-sum property if every element is a sum of two commuting units. In this note, we present some sufficient or necessary conditions for the matrix ring over a commutative local ring to have the strong 2-sum property.

A unit-picker is a map [Formula: see text] that associates to every ring [Formula: see text] a well-defined set [Formula: see text] of central units in [Formula: see text] which contains [Formula: see text], is invariant under isomorphisms of rings, is closed under taking inverses, and which satisfies certain set containment conditions for quotient rings, corner rings and matrix rings. Let [Formula: see text] be a unit-picker. A ring [Formula: see text] is called [Formula: see text] if [Formula: see text] and [Formula: see text] if [Formula: see text] and [Formula: see text] if [Formula: see text]. An extensive study of these rings is conducted, and their connections with strongly nil [Formula: see text]-clean rings and semi [Formula: see text]-Boolean rings are investigated. When [Formula: see text] is specified, known results of [Formula: see text]-rings, [Formula: see text]-rings and [Formula: see text]-rings are obtained and new results are proved.

An element a in a ring R is left annihilator-stable (or left AS) if, whenever $Ra+{\rm l}(b)=R$ with $b\in R$ , $a-u\in {\rm l}(b)$ for a unit u in R, and the ring R is a left AS ring if each of its elements is left AS. In this paper, we show that the left AS elements in a ring form a multiplicatively closed set, giving an affirmative answer to a question of Nicholson [J. Pure Appl. Alg.221 (2017), 2557–2572.]. This result is used to obtain a necessary and sufficient condition for a formal triangular matrix ring to be left AS. As an application, we provide examples of left AS rings R over which the triangular matrix rings ${\mathbb T}_n(R)$ are not left AS for all $n\ge 2$ . These examples give a negative answer to another question of Nicholson [J. Pure Appl. Alg.221 (2017), 2557–2572.] whether R/J(R) being left AS implies that R is left AS.

The isocitrate dehydrogenase (IDH1/2) mutations are frequent genetic abnormalities in the majority of WHO grade II/III glioma and secondary GBM. IDH1-mutated (IDH1Mut) glioma exhibits distinctive patterns in cancer biology and metabolism. In the present study, we showed that bone morphogenetic proteins (BMP4) are significantly upregulated in IDH1Mut glioma. Further, we demonstrated that cancer-associated BMP4 is secreted to tumor microenvironment, which enhances the tumor migration and invasion through an autocrine manner. Mechanistically, BMP4 activates its receptor and concomitant SMAD1/5/8 signaling, which potentiates Wnt/β-catenin signaling by enhancing Frizzled receptor expression. LDN-193189, a selective BMP receptor inhibitor, prolonged the overall survival of mice bearing IDH1-mutated intracranial xenografts by limiting BMP/catenin signaling. These findings demonstrate the pivotal role of BMP4 on tumor aggressiveness in IDH1Mut gliomas, suggesting a possible therapeutic strategy for this type of malignancy.

Background: We aimed to compare the outcomes of end-to-end descending hypoglossal-facial anastomosis (eeDHFA) and end-to-side hypoglossal-facial anastomosis (esHFA) in patients with complete facial paralysis after vestibular schwannoma (VS) surgery. Methods: This retrospective study included 52 patients with complete nerve damage identified during previous VS removal or on electromyography during follow-up. Postoperative facial palsy was evaluated using the House-Brackmann (HB) facial nerve grading system. Postoperative hemiglossal atrophy and swallowing were assessed using Martins’ grading system and the water-swallowing test, respectively. Hoarseness was also recorded if present. Results: The median time from VS resection to anastomosis was not significantly different between the two groups (p=0.062). The median follow-up time showed no significant differences between groups (eeDHFA: 17 months; esHFA: 14 months; p=0.446). We found no significant differences in the number of favourable (HB I-III) or unfavourable (HB IV-VI) outcomes for facial nerve function in the last follow-up (p=0.924). Only one patient from each group developed hemi-tongue myoparalysis. No patient experienced swallowing dysfunction or hoarseness. Conclusions: We concluded that eeDHFA is as effective as esHFA as a surgical method for the treatment of facial palsy after VS surgery. Since eeDHFA represents a simple technique for facial reanimation, it could therefore be considered as an alternative surgical option for patients affected by complete facial paralysis after VS surgery.

A large volume (more than 4.0 million m3) of treated construction and demolition waste (CDW) is planned to be used in the construction of the Xi’an-Xianyang north loop line freeway in West China. These CDW were preliminarily separated into broken concretes, bricks, and porcelains in the treatment plants. In this study, a total of 190 CDW samples including 80 concretes, 80 bricks, 20 porcelains, and 10 mixed samples were collected from five treatment plants. Five farmland soil samples near treatment plants were collected as controls. The contents of 10 elements including cadmium (Cd), arsenic (As), copper (Cu), nickel (Ni), zinc (Zn), chromium (Cr), lead (Pb), manganese (Mn), silver (Ag), and mercury (Hg) in these samples were measured. The contents of 8 elements (Cu, Ni, Zn, Cr, Pb, Mn, Ag, and Hg) in all CDW samples were qualified for the third-level criterion of the Standard of Soil Environment (GB15618-2008). However, Cd contents in 37 concretes, 34 bricks, 6 porcelain samples, and 4 mixed CDW samples exceeded the national third-level standards (1 mg/kg) in GB15618-2008. And As contents in 28 concretes, 21 bricks, 5 porcelain samples, and 3 mixed CDW samples were higher than the national third-level standards (40 mg/kg). The total exceeding standard rates (ESRs) of Cd and As were 42.6% and 30%, respectively. The leaching tests for Cd and As were also done due to their higher ESRs. The results showed that the release amounts (μg/kg) of Cd and As from CDW were increased with increasing liquid to solid ratio (0.4–10 l/kg) but decreased with increasing pH (4–7). The leached concentrations of Cd and As from four types of CDW samples were both in a descending order: brick, mixed materials, concrete, and porcelain. The measured concentrations (μg/L) of Cd and As in leachate were all lower than second-grade criteria of Standard for Groundwater Quality (GB3838-2002). By comparing the leached concentrations of Cd and As with the value in European criteria (EU Council Decision 2003/33/EC) for hazardous wastes, all the CDW samples should be classified as inert or non-hazardous wastes. Thus, it could be concluded that heavy metals in these CDW would not pollute surrounding soil, surface water, and groundwater environment when applied in freeway construction.

Let [Formula: see text] be a Morita context. For generalized fine (respectively, generalized unit-fine) rings [Formula: see text] and [Formula: see text], it is proved that [Formula: see text] is generalized fine (respectively, generalized unit-fine) if and only if, for [Formula: see text] and [Formula: see text], [Formula: see text] implies [Formula: see text] and [Formula: see text] implies [Formula: see text]. Especially, for fine (respectively, unit-fine) rings [Formula: see text] and [Formula: see text], [Formula: see text] is fine (respectively, unit-fine) if and only if, for [Formula: see text] and [Formula: see text], [Formula: see text] implies [Formula: see text] and [Formula: see text] implies [Formula: see text]. As consequences, (1) matrix rings over fine (respectively, unit-fine, generalized fine and generalized unit-fine) rings are fine (respectively, unit-fine, generalized fine and generalized unit-fine); (2) a sufficient condition for a simple ring to be fine (respectively, unit-fine) is obtained: a simple ring [Formula: see text] is fine (respectively, unit-fine) if both [Formula: see text] and [Formula: see text] are fine (respectively, unit-fine) for some [Formula: see text]; and (3) a question of Cǎlugǎreanu [1] on unit-fine matrix rings is affirmatively answered.

Glioblastoma is the most common primary brain malignancy with limited treatment options. EphA2 is a tumor-associated-antigen overexpressed in glioblastoma. Pre-clinical studies have demonstrated the promise of EphA2-redirected CAR T-cells against glioblastoma. We conduct the first-in-human trial of EphA2-redirected CAR T-cells in patients with EphA2-positive recurrent glioblastoma and report the results of three patients enrolled as the first cohort receiving the starting dosage (1×106 cells/kg). A single infusion of EphA2-redirected CAR T-cells was administrated intravenously, with the lymphodepletion regimen consisting of fludarabine and Cyclophosphamide. In two patients, there was grade 2 cytokine release syndrome accompanied by pulmonary edema, which resolved completely with dexamethasone medication. Except that, there was no other organ toxicity including neurotoxicity. In both the peripheral blood and cerebral-spinal-fluid, we observed the expansion of CAR T-cells which persisted for more than four weeks. In one patient, there was a transit diminishment of the tumor. Among these three patients, one patient reported SD and two patients reported PD, with overall survival ranging from 86 to 181 days. At the tested dose level (1×106 cells/kg), intravenously infusion of EphA2-rediretected CAR T-cells were preliminary tolerable with transient clinical efficacy. Future study with adjusted dose and infusion frequency of CAR T-cells is warranted.Trial Registration NumbersNCT 03423992

Chordoma, a malignant bone cancer, is highly resistant to conventional therapeutic approaches; this greatly limits radio- and chemotherapeutic options and disease management. In the present study, we investigated three patient-derived chordoma cell lines to elucidate the molecular mechanism of resistance to therapeutics. An in vitro high-throughput chemical screening assay and an in vivo xenograft model were used to identify novel chemosensitizers for chordoma. We found that patient-derived chordoma cell lines recapitulated disease phenotypes, which were highlighted by robust resistance to medical therapy manifested as lack of DNA damage accumulation. Mechanistically, the PARP DNA repair pathway was found to play a central role in this resistance. Chemical screening confirmed that PARP inhibitors could strikingly enhance temozolomide (TMZ) therapy in chordoma cells. Combining the FDA-approved PARP inhibitor, olaparib, with chemotherapeutics not only potentiated DNA damage accumulation, cell cycle arrest, and apoptosis in vitro but also suppressed chordoma xenograft expansion in vivo. We conclude that combining PARP inhibition with TMZ could be an effective therapeutic approach for the clinical management of chordoma. KEY MESSAGES: The PARP DNA repair pathway enhances chemoresistance in chordoma cells. Combining PARP inhibitors with genotoxic agents induces chordoma cell cytotoxicity. PARP inhibitor combining with temozolomide suppresses growth of chordoma in vivo.

This paper is about rings $R$ for which every element is a sum of a tripotent and an element from the Jacobson radical $J(R)$. These rings are called semi-tripotent rings. Examples include Boolean rings, strongly nil-clean rings, strongly 2-nil-clean rings, and semi-boolean rings. Here, many characterizations of semi-tripotent rings are obtained. Necessary and sufficient conditions for a Morita context (respectively, for a group ring of an abelian group or a locally finite nilpotent group) to be semi-tripotent are proved.

Phenolic compounds have caused different degrees of negative impacts in aquatic environment. Amino acids, humic acids and carbohydrates are the three dominant types of dissolved natural organic matter (DNOM) in natural water bodies. In this research, the influences of dissolved natural organic matter (DNOM) on the adsorption behaviors of phenol, 2,4-dichlorophenol (DCP) and 2,4,6-trichlorophenol (TCP) in Weihe River suspended sediment were studied by using DL-alanine, fulvic acid and glucose as the representatives of the three types of DNOM. The results of batch adsorption experiments showed that, without DNOM, Langmuir and Freundlich had good fitting effects on the three phenolic compounds and their maximum adsorption capacities were 21.580, 27.768 and 24.758 mg/kg respectively. The presence of amino acids increased adsorption capacities of the phenol and TCP on suspended sediments by approximately 13.84% and 11.56% respectively. The existence of fulvic acid and glucose positively affected the adsorption of phenol, DCP and TCP on suspended sediment. The isothermal adsorption in the coexistence of different DNOM were more consistent with the nonlinear adsorption. Other influence factors including pH, ionic strength and temperature can influence the adsorption behavior to different extents. The impact of dissolved natural organic matter (DNOM) on adsorption should be fully considered when mastering environmental migration and transformation behaviors of phenolic compounds in water-sediments environment.

A unit-picker is a map [Formula: see text] that associates to every ring [Formula: see text] a well-defined set [Formula: see text] of central units in [Formula: see text] which contains [Formula: see text] and is invariant under isomorphisms of rings and closed under taking inverses, and which satisfies certain set containment conditions for quotient rings, corner rings and matrix rings. Let [Formula: see text] be a unit-picker. A ring [Formula: see text] is called (strongly) nil [Formula: see text]-clean if for each [Formula: see text], [Formula: see text] where [Formula: see text], [Formula: see text] and [Formula: see text] is nilpotent (and [Formula: see text]). An extensive study of (strongly) nil [Formula: see text]-clean rings is conducted. When [Formula: see text] is specified, known results of the much-studied (strongly) nil-clean rings and weakly nil-clean rings are re-proved and new results of other nil-clean-like rings are obtained.

As introduced by Cǎlugǎreanu and Lam in [G. Cǎlugǎreanu and T. Y. Lam, Fine rings: a new class of simple rings, J. Algebra Appl. 15(9) (2016) 1650173, 18 pp.], a fine ring is a ring whose every nonzero element is the sum of a unit and a nilpotent. As a natural generalization of fine rings, a ring is called a generalized fine ring if every element not in the Jacobson radical is the sum of a unit and a nilpotent. Here some known results on fine rings are extended to generalized fine rings. A notable result states that matrix rings over generalized fine rings are generalized fine, extending the important result in [G. Cǎlugǎreanu and T. Y. Lam, Fine rings: a new class of simple rings, J. Algebra Appl. 15(9) (2016) 1650173, 18 pp.] that matrix rings over fine rings are fine.

An idempotent in a ring is called fine (see G. Călugăreanu and T. Y. Lam, Fine rings: A new class of simple rings, J. Algebra Appl. 15(9) (2016) 18) if it is a sum of a nilpotent and a unit. A ring is called an idempotent-fine ring (briefly, an [Formula: see text] ring) if all its nonzero idempotents are fine. In this paper, the properties of [Formula: see text] rings are studied. A notable result is proved: The diagonal idempotents [Formula: see text] ([Formula: see text]) are fine in the matrix ring [Formula: see text] for any unital ring [Formula: see text] and any positive integer [Formula: see text]. This yields many classes of rings over which matrix rings are [Formula: see text].

Hypoxia is common in Glioblastoma (GBM). By regulating the 'hypoxia signaling cascade', hypoxia affects several processes including cell proliferation, invasion, and angiogenesis. Some studies have revealed that signal transducer and activator of transcription (STAT), including STAT1, is abnormal under hypoxia in several cancers. Here, we investigated the role of STAT1 under hypoxia in glioma progression. We found that STAT1 was downregulated under a hypoxic condition in U251 and U373. STAT1 overexpression can not only decrease proliferation, migration and invasion in U251 and U373 but also inhibit tube formation of HBMECs. Moreover, overexpression of STAT1 decreased tumor growth and prolonged the overall survival of xenograft mice. We also showed that STAT1 overexpression inhibited the expression of HIF-1α and VEGF-A. Our work suggests that STAT1 plays a pivotal role as a tumor suppressor in glioma under hypoxia, and it could be a potential new therapeutic target in glioma.

An element in a ring is clean (or, unit-regular) if it is the sum (or, the product) of an idempotent and a unit, and is nil-clean if it is the sum of an idempotent and a nilpotent. Firstly, we show that Jacobson’s lemma does not hold for nil-clean elements in a ring, answering a question posed by Kosan, Wang and Zhou (2016). Secondly, we present new counter-examples to Diesl’s question whether a nil-clean element is clean in a ring. Lastly, we give new examples of unit-regular elements that are not clean in a ring. The rings under consideration in our examples are particular subrings of $$\mathbb{M}_{2}(\mathbb{Z})$$ .

Purpose: Cluster I pheochromocytomas and paragangliomas (PCPGs) tend to develop malignant transformation, tumor recurrence, and multiplicity. Transcriptomic profiling suggests that cluster I PCPGs and other related tumors exhibit distinctive changes in the tricarboxylic acid (TCA) cycle, the hypoxia signaling pathway, mitochondrial electron transport chain, and methylation status, suggesting that therapeutic regimen might be optimized by targeting these signature molecular pathways. Experimental Design: In the present study, we investigated the molecular signatures in clinical specimens from cluster I PCPGs in comparison with cluster II PCPGs that are related to kinase signaling and often present as benign tumors. Results: We found that cluster I PCPGs develop a dependency to mitochondrial complex I, evidenced by the upregulation of complex I components and enhanced NADH dehydrogenation. Alteration in mitochondrial function resulted in strengthened NAD+ metabolism, here considered as a key mechanism of chemoresistance, particularly, of succinate dehydrogenase subunit B (SDHB)-mutated cluster I PCPGs via the PARP1/BER DNA repair pathway. Combining a PARP inhibitor with temozolomide, a conventional chemotherapeutic agent, not only improved cytotoxicity but also reduced metastatic lesions, with prolonged overall survival of mice with SDHB knockdown PCPG allograft. Conclusions: In summary, our findings provide novel insights into an effective strategy for targeting cluster I PCPGs, especially those with SDHB mutations. Clin Cancer Res; 24(14); 3423–32. ©2018 AACR.

It is proved that a semiperfect module is lifting if and only if it has a projective cover preserving direct summands. Three corollaries are obtained: (1) every cyclic module over a ring R is lifti...

A submodule N of a module M is δ-small in M if N+X≠M for any proper submodule X of M with M∕X singular. A projective δ-cover of a module M is a projective module P with an epimorphism to M whose kernel is δ-small in P. A module M is called δ-semiperfect if every factor module of M has a projective δ-cover. In this paper, we prove various properties, including a structure theorem and several characterizations, for δ-semiperfect modules. Our proofs can be adapted to generalize several results of Mares [8] and Nicholson [11] from projective semiperfect modules to arbitrary semiperfect modules.

For a semisimple module M over a ring R with R / J ( R ) Boolean, every endomorphism of M is a sum of an idempotent endomorphism and a locally nilpotent endomorphism. As a consequence, it is proved that, for a vector space V over a division ring D, every linear transformation of V is a sum of an idempotent linear transformation and a locally nilpotent linear transformation if and only if D ≅ F 2 . This can be seen as an answer to the “local” version of a question raised by Breaz et al. in [1] on nil-cleanness of the ring of linear transformations of an infinite dimensional vector space.

A ring $R$ is a UU ring if every unit is unipotent, or equivalently if every unit is a sum of a nilpotent and an idempotent that commute. These rings have been investigated in C\u{a}lug\u{a}reanu \cite{C} and in Danchev and Lam \cite{DL}. In this paper, two generalizations of UU rings are discussed. We study rings for which every unit is a sum of a nilpotent and an idempotent, and rings for which every unit is a sum of a nilpotent and two idempotents that commute with one another.

Objective The semisitting position (SSP) and lateral position (LP) in vestibular schwannoma (VS) surgery each have advantages and disadvantages, and which position is superior overall is debatable. Our objective was to determine the optimal position for surgical treatment of VSs with a diameter ≥3 cm. Methods We retrospectively evaluated consecutive patients with a large VS treated between January 2010 and July 2020. Patients were grouped by surgical position and analyzed. Results We enrolled 259 patients (LP group, n = 156; SSP group, n = 103). The resection extent was not significantly different between the SSP (gross-total resection [GTR], n = 89 [88.1%], near-total resection [NTR], n = 10 [9.9%], subtotal resection [STR], n = 2 [2.0%]) and LP (GTR, n = 125 [80.1%]; NTR, n = 24 [15.4%]; STR, n = 7 [4.5%]) groups. The rate of GTR with facial nerve (FN) functional preservation was higher in the SSP group than in the LP group (P = 0.014) at eight days after the operation. However, during follow-up (SSP group median, 31.5 months; LP group median, 19.5 months), there was no significant between-group difference in FN functional preservation. Two patients in the SSP group required conversion to the LP due to severe intraoperative venous air embolism (VAE). Conclusion Compared with the LP, the SSP did not produce significantly better FN outcomes in patients with a large VS. The duration of surgery was significantly longer in SSP cases than in LP cases. Given the risk of VAE associated with the SSP, the selection of the optimal surgical position should be made with caution on an individual basis.

In this corrigendum, statement (5) of Proposition 4.4 is reformulated and an example is given to show that this correction is necessary.