Exploring the Use of "Honorary Transition Metals" To Push the Boundaries of Planar Hypercoordinate Alkaline-Earth Metals.

The quest for planar hypercoordinate atoms (phA) beyond six has predominantly focused on transition metals, with dodecacoordination being the highest reported thus far. Extending this bonding scenario to main-group elements, which typically lack d orbitals despite their larger atomic radius, has posed significant challenges. Intrigued by the potentiality of covalent bonding formation using the d orbitals of the heavier alkaline-earth metals (Ae = Ca, Sr, Ba), the so-called "honorary transition metals", we aim to push the boundaries of planar hypercoordination. By including rings formed by 12-15 atoms of boron-carbon and Ae centers, we propose a design scheme of 180 candidates with a phA. Further systematic screening, structural examination, and stability assessments identified 10 potential clusters with a planar hypercoordinate alkaline-earth metal (phAe) as the lowest-energy form. These unconventional structures embody planar dodeca-, trideca-, tetradeca-, and pentadecacoordinate atoms. Chemical bonding analyses reveal the important role of Ae d orbitals in facilitating covalent interactions between the central Ae atom and the surrounding boron-carbon rings, thereby establishing a new record for coordination numbers in the two-dimensional realm.

Survival benefits of adjuvant chemotherapy for patients with residual pathologic disease after neoadjuvant chemotherapy and surgery for locally advanced esophageal squamous cell carcinoma.

BACKGROUND: Although preoperative neoadjuvant chemotherapy (NACT) or chemoradiation is the current standard of care for esophageal cancer in China, the impact of subsequent adjuvant therapy on patient prognosis remains unknown. This study aims to analyze the effect of adjuvant chemotherapy (ACT) on the survival rates of patients who have achieved a non-pathological complete response (non-pCR) after NACT and subsequent surgery. METHODS: We reviewed the data of 2193 patients with locally advanced thoracic esophageal squamous cell carcinoma (ESCC) who underwent radical surgery between January 2006 and January 2016. Of these patients, 46 received NACT and ACT, while 109 received NACT only. Propensity score matching was used to compare 86 patients, with 43 patients in the NACT + ACT group and 43 patients in the NACT group. Univariate analysis was performed using the Kaplan-Meier method and log-rank test, while Cox regression analysis was used for multivariate analysis. RESULTS: Multivariate analysis revealed that pathological lymph node status (positive vs negative) (P < .001) and treatment modalities (NACT + ACT vs NACT) (P = .005) were independent prognostic factors. There was a significant difference in long-term survival rates between the NACT + ACT and NACT groups, with 5-year survival rates of 55.8% vs 39.5%, respectively (χ2 = 4.270, P = .039). In patients with ypN+ status, the 5-year survival rate was 31.8% for those who received ACT after NACT and surgery, compared to 10.0% for those who did not receive additional ACT (χ2 = 6.101, P = .014). The corresponding percentages in patients with ypN- were 81.0% and 65.2%, respectively (χ2 = 1.993, P = .158). CONCLUSION: Adjuvant chemotherapy should be recommended for locally advanced ESCC patients with residual cancer after NACT and surgery, especially for patients with nodal metastases after NACT.

Clusters and bulky Lewis acid protected complexes with planar hexacoordinate beryllium and magnesium.

Planar hexacoordination (ph) is only rarely reported in the literature. So far, only a few neutral and cationic molecules possessing phE (E = C, Si, B, Al, Ga) in the most stable isomer are predicted theoretically. Present electronic structure calculations report hitherto unknown anionic planar hexcoordinate beryllium and magnesium, phBe/Mg, as the most stable isomer. Global minimum searches show that the lowest energy structure of BeC6M3- (M = Al, Ga) and MgC6M3- (M = Ga, In, Tl) is the D3h symmetric phBe/Mg clusters, where beryllium/magnesium is covalently bonded with six carbon centers and M is located in a bridging position between two carbon centers. These global minimum phBe/Mg clusters are highly kinetically stable against isomerization, facilitating the experimental confirmation by photoelectron spectroscopy. Noteworthy is the fact that the phBe/Mg center is linked with carbon centers through three 7c-2e delocalized σ bonds and three 7c-2e π bonds, making the cluster double aromatic (σ + π) in nature. The bonding between the Be/Mg and outer ring moiety can be best expressed as an electron-sharing σ-bond between the s orbital of Be+/Mg+ and C6M32- followed by three dative interactions involving empty pπ and two in-plane p orbitals of Be/Mg. Furthermore, Lewis basic M centers of the title clusters can be passivated through the complexation with bulky Lewis acid, 9-boratriptycene, lowering the overall reactivity of the cluster, which can eventually open up the possibility of their large-scale syntheses.

B7 Be6 B7 : A Boron-Beryllium Sandwich Complex.

Planar boron clusters have often been regarded as "π-analogous" to aromatic arenes because of their similar delocalized π-bonding. However, unlike arenes such as C5 H5 - and C6 H6 , boron clusters have not previously shown the ability to form sandwich complexes. In this study, we present the first sandwich complex involving beryllium and boron, B7 Be6 B7 . The global minimum of this combination adopts a unique architecture having a D6h geometry, featuring an unprecedented monocyclic Be6 ring sandwiched between two quasi-planar B7 motifs. The thermochemical and kinetic stability of B7 Be6 B7 can be attributed to strong electrostatic and covalent interactions between the fragments. Chemical bonding analysis shows that B7 Be6 B7 can be considered as a [B7 ]3- [Be6 ]6+ [B7 ]3- complex. Moreover, there is a significant electron delocalization within this cluster, supported by the local diatropic contributions of the B7 and Be6 fragments.

Be4 B12 + : A Covalently Bonded Archimedean Beryllo-Borospherene.

A new class of beryllium-boron clusters, beryllo-borospherene, is described herein theoretically. When beryllium is gradually added to the B12 motif, it undergoes drastic structural modifications. The global minimum of the Be4 B12 + cluster is an Archimedean beryllo-borospherene in a 2 A1 electronic ground state, composed of four boron triangles linked at each corner, resulting in a truncated tetrahedron with four B6 rings capped with four beryllium atoms. Beryllium forms strong bonding with the boron clusters through strong electrostatic and covalent interactions. For instance, the bonding between a beryllium atom and Be3 B12 unit is best described as a Be+ fragment in a 2 P excited state forming a strong and polarized electron-sharing bond with Be3 B12 , followed by several dative interactions by employing its vacant s, p, and very high-lying d orbitals. Counterintuitively, for an s-block element, the p orbitals of beryllium are the most crucial atomic orbitals for bonding rather than s orbitals.

Prognostic value of Siglec-15 expression in patients with solid tumors: A meta-analysis.

Background: Siglec-15 is expressed in a variety of cancers. However, the role of Siglec-15 in the prognosis of cancer patients remains controversial. Therefore, we conducted a meta-analysis to clarify the potential prognostic value of Siglec-15 in solid tumors. Methods: The PubMed, Web of Science, Embase and CNKI databases were comprehensively searched to identify studies assessing the effect of Siglec-15 on the survival of cancer patients. Hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS), progression-free survival (PFS) and disease-specific survival (DSS) from individual studies were evaluated. Results: The data from 13 observational studies consisting of 1376 patients were summarized. Elevated baseline Siglec-15 expression was significantly correlated with poor OS (pooled HR = 1.28, 95% CI: 1.05-1.56; P = 0.013). However, high Siglec-15 expression predicted a significantly better DSS (pooled HR = 0.73 (95% CI: 0.57-0.94; P = 0.015) but not PFS (pooled HR = 1.49, 95% CI: 0.46-4.87; P=0.510). In addition, high Siglec-15 expression was not associated with PD-L1 (OR=0.64, 95% CI: 0.42-0.95; P = 0.028). High Siglec-15 expression was associated with male sex (OR = 1.39, 95% CI: 1.05-1.84; P = 0.022), larger tumor size (OR = 1.896, 95% CI: 1.26-2.9; P = 0.002), and advanced tumor-node-metastasis (TNM) stage (OR = 1.84; 95% CI: 1.19-2.84; P =0.006) in solid tumors. Conclusions: This updated study suggested the expression of Siglec-15 is significantly associated with poor outcomes in human solid tumors, but further studies are needed to determine the prognostic value of Siglec-15 in solid tumors.

B7-H4 overexpression contributes to poor prognosis and drug-resistance in triple-negative breast cancer.

BACKGROUND: The expression of the immunoregulatory protein B7-H4 has been reported in many types of cancer, including breast cancer. However, its role in triple-negative breast cancer (TNBC), especially its correlation with patients' prognosis and chemoresistance remains unclear. METHODS: The expression of B7-H4 in TNBC tissues and cell lines were measured with Real-Time PCR and western blotting. 65 cases of TNBC tissue samples and adjacent non-tumor tissue samples were analyzed by immunochemistry to demonstrate the correlation between the B7-H4 expression and clinicopathological characteristics. In vitro studies assessed mAb MIH43 alone and in combination with transfecting B7-H4 siRNA on the growth of chemosensitive and chemoresistant TNBC cell lines by CCK-8 and apoptotic enzyme-linked immunosorbent assay (ELISA). RESULTS: B7-H4 expression was detected positive in 59 of 65 (90.8%) different stage TNBC patients, especially in the samples of recurrence TNBC patients after receiving neoadjuvant chemotherapy treatment. Survival curves showed that patients with B7-H4 overexpression had significantly shorter survival and recurrence time than those with low B7-H4 expression (p < 0.005). Univariate and multivariate COX regression analysis demonstrated that B7-H4 was an independent predictor for advanced tumor stage. The monoclonal antibody of B7-H4 has the potential anti-proliferative effects on inhibiting the chemoresistant TNBC cell lines and increasing the sensitivity of TNBC cell lines to doxorubicin, paclitaxel or carboplatin. RNAi-mediated silencing of B7-H4 in TNBC cells enhanced drug-induced apoptosis via inhibiting PTEN/PI3K/AKT pathway, whereas reexpression of B7-H4 in B7-H4 knockdown and low B7-H4 expressing cells increased the phosphorylation of PI3K and AKT along with restoration of PETN expression. CONCLUSIONS: Our data show that B7-H4 is a biomarker indicative of a poor prognosis in TNBC patients and at least partially downregulated in chemoresistance via PTEN/PI3K/AKT pathway. Targeting B7-H4 might provide an attractive therapeutic approach specifically for TNBC patients.

Prognostic significance of the location of metastatic lymph nodes in patients with adenocarcinoma of the oesophagogastric junction.

BACKGROUND: Adenocarcinoma of the oesophagogastric junction (AEG) potentially metastasizes to lymph nodes (LNs) in the abdomen and thorax. The aim of this study was to analyse the impact of metastatic LN location on prognosis in patients with AEG. METHODS: From May 2000 to March 2002, 645 patients with AEG underwent resection in our hospital. There were 525 males and 120 females, aged from 31 to 78 years (median = 60 years). Follow-up was carried out by correspondence every 6 months. N-classification according to the number (0, 1-2, 3-6, >6; N0-3), station (0, 1, 2, 3; S0-3) or field (0, 1 (abdominal or mediastinal), 2 (abdominal and mediastinal); F0-2) of LN metastasis and other prognostic factors were evaluated by univariate and multivariate survival analyses. RESULTS: Of the 645 patients, 307 (47.6%) had LN metastasis. The 5-year survival rate for patients with LN metastases was 16.0% compared to 36.8% for those without LN metastases (P = 0.000). The length of tumour, and the number, station and field of the LN metastasis were independent prognostic factors by multivariate analysis. However, when patients without LN metastasis were excluded from the survival analysis by log-rank test, there were significant differences only in patients with F1 versus F2 LN metastasis, with 5-year survival rates of 14.4% and 8.0%, respectively (P = 0.022). CONCLUSION: The presence of LN metastases concurrently in both the abdomen and mediastinum is a significant adverse prognostic factor for patients with AEG, and should be included in the future TNM staging system.

Using variable combination population analysis for variable selection in multivariate calibration.

Variable (wavelength or feature) selection techniques have become a critical step for the analysis of datasets with high number of variables and relatively few samples. In this study, a novel variable selection strategy, variable combination population analysis (VCPA), was proposed. This strategy consists of two crucial procedures. First, the exponentially decreasing function (EDF), which is the simple and effective principle of 'survival of the fittest' from Darwin's natural evolution theory, is employed to determine the number of variables to keep and continuously shrink the variable space. Second, in each EDF run, binary matrix sampling (BMS) strategy that gives each variable the same chance to be selected and generates different variable combinations, is used to produce a population of subsets to construct a population of sub-models. Then, model population analysis (MPA) is employed to find the variable subsets with the lower root mean squares error of cross validation (RMSECV). The frequency of each variable appearing in the best 10% sub-models is computed. The higher the frequency is, the more important the variable is. The performance of the proposed procedure was investigated using three real NIR datasets. The results indicate that VCPA is a good variable selection strategy when compared with four high performing variable selection methods: genetic algorithm-partial least squares (GA-PLS), Monte Carlo uninformative variable elimination by PLS (MC-UVE-PLS), competitive adaptive reweighted sampling (CARS) and iteratively retains informative variables (IRIV). The MATLAB source code of VCPA is available for academic research on the website: http://www.mathworks.com/matlabcentral/fileexchange/authors/498750.

Investigation of cholecystokinin receptors in the human lower esophageal sphincter.

AIM: To compare the binding of cholecystokinin (CCK)-8 to CCK receptors in sling and clasp fibers of the human lower esophageal sphincter. METHODS: Esophageal sling and clasp fibers were isolated from eight esophagectomy specimens, resected for squamous cell carcinoma in the upper two thirds of the esophagus, which had been maintained in oxygenated Kreb's solution. Western blot was used to measure CCK-A and CCK-B receptor subtypes in the two muscles. A radioligand binding assay was used to determine the binding parameters of (3)H-CCK-8S to the CCK receptor subtypes. The specificity of binding was determined by the addition of proglumide, which blocks the binding of CCK to both receptor subtypes. RESULTS: There was no significant difference between the sling and clasp fibers of the human lower esophageal sphincter in the amount of CCK-A [integrated optical density (IOD) value: 22.65 ± 0.642 vs 22.328 ± 1.042, P = 0.806] or CCK-B receptor protein (IOD value: 13.20 ± 0.423 vs 12.45 ± 0.294, P = 0.224) as measured by Western blot. The maximum binding of radio-labeled CCK-8S was higher in the sling fibers than in the clasp fibers (595.75 ± 3.231 cpm vs 500.000 ± 10.087 cpm, P < 0.001) and dissociation constant was lower (K(d): 1.437 ± 0.024 nmol/L vs 1.671 ± 0.024 nmol/L, P < 0.001). The IC50 of the receptor specific antagonists were lower for the CCK-A receptors than for the CCK-B (P < 0.01). CONCLUSION: CCK binding modulates the contractile function of the lower esophageal sphincter through differential binding to the CCK-A receptor on the sling and clasp fibers.

[Effect of erythromycin on electrical activity and gastric emptying of the intrathoracic stomach after esophagectomy for esophageal cancer].

OBJECTIVE: To investigate the effect of erythromycin on electrical activity and emptying of the intrathoracic stomach after esophagectomy for esophageal cancer. METHODS: Thirty patients undergoing esophagectomy for cancer and esophagogastrostomy above the aortic arch were divided into the study group (n=15) and the control group (n=15). Electrogastrography and radionuclide gastric emptying were examined for these patients before and 1, 3, 6, 12 months after surgery. Patients in the study group received erythromycin (0.25 g tid po) for 1 week before examination. RESULTS: The wave amplitude (Uv), dominant frequency (CPM) and percentage of normal slow wave (%) of electrogastrogram decreased after surgery and returned to normal at the first postoperative month in the study group and the 12th postoperative month in the control group (P>0.05). Gastric emptying was significantly delayed after esophagectomy, and returned to normal one year after operation in the study group (P>0.05). However, gastric emptying remained abnormal in the control group (P<0.01). CONCLUSIONS: Erythromycin improves electrical activity and emptying of the stomach after esophagectomy for cancer. Gastric emptying recovery later than the recovery of electrical activity, which may be related to gastric ischemia and edema.

Expression of dopamine receptors in human lower esophageal sphincter.

BACKGROUND AND AIM: Dopamine (DA) is considered to be an important modulator of enteric function. Recent experiments have suggested that DA receptors are widely expressed in animal gastrointestinal tract. The aim of this study was to explore the expression of DA receptors (D(1) R, D(2) R, D(3) R, D(4) R, D(5) R) in sling fibers and clasp fibers from the human lower esophageal sphincter (LES). METHODS: Muscle strips of sling and clasp fibers from the LES were obtained from patients undergoing esophago-gastrectomy, and circular muscle strips from the esophagus and stomach were used as controls. Reverse transcription-polymerase chain reaction and western blotting were used to determine the expression of the five subtypes of DA receptors. RESULTS: Messenger RNA and protein for three of five DA receptors were identified in the sling and clasp fibers of the LES. Expression was highest for D(1) R, then D(5) R and D(2) R in decreasing levels. D(3) R and D(4) R mRNA and protein were not identified in the muscle strips. CONCLUSION: D(1) R, D(2) R, D(5) R can be detected in the human LES, and probably contribute to LES function. D(3) R and D(4) R are not expressed, and probably do not contribute to LES function in humans.

[Antireflux anastomosis following resection of esophageal cancer].

OBJECTIVE: To investigate the antireflux effects of a modified Nissen fundoplication following esophagectomy for cancer. METHODS: From March 2006 to March 2007, 70 patients with esophageal cancer were divided into two groups randomly. Esophagogastrostomy with a stapler only was perform in 35 patients as controls (group C), and a modified Nissen fundoplication was added after esophagogastrostomy with stapler in the other 35 patients as observed group (group O). There were 48 male and 22 female, ranging in age from 47 to 77 years (mean 60.1 years). The operative morbidity and mortality were recorded. Fourty-nine patients were followed at 3 months after surgery, and the questionnaire of life quality (EORTC QLQ C-30) was conducted in 24 patients in group C and 25 patients in group O. Thirty patients were examined with esophageal manometry, 24 h pH monitoring and gastroscopy. There were 16 patients in group C and 14 patients in group O. RESULTS: There was no significant difference in postoperative morbidity between the two groups (P > 0.05). However, the scores of heart burn and regurgitation in the group O were less than in group C (P = 0.041 and 0.034 respectively), but there was no difference in scores of dysphagia between the two groups (P = 0.677). The pressure at the anastomotic site was higher than that in the stomach in group O (P = 0.032), but not in group C (P = 0.448). DeMeester score in group O was 53 ± 46, compared to 140 ± 103 in group C (P = 0.043). The score of esophagitis was 0.9 ± 0.8 in group O, which was lower than 1.6 ± 1.0 in group C (P = 0.041). CONCLUSIONS: Addition of modified Nissen fundoplication after esophagectomy and esophagogastrostomy for cancer significantly increases the pressure at the anastomotic site, thus reduces the extent of gastroesophageal reflux, which leads to the reduction of the extent of reflux esophagitis and the improvement of the quality of life.