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Abstract: Stem cells holding great promises in regenerative medicine have the potential to be differentiated to a specific cell type through genetic manipulation. However, conventional ways of gene transfer to such progenitor cells suffer from a number of disadvantages particularly involving safety and efficacy issues. Here, we report on the development of a bio-functionalized inorganic nano-carrier of DNA by embedding fibronectin and E-cadherin chimera on the carrier, leading to its high affinity interactions with embryonic stem cell surface and accelerated trans-gene delivery for subsequent expression. While only apatite nano-particles were very inefficient in transfecting embryonic stem cells, fibronectin-anchored particles and to a more significant extent, fibronectin and E-cadherin-Fc-associated particles dramatically enhanced trans-gene delivery with a value notably higher than that of commercially available lipofection system. The involvement of both cell surface integrin and E-cadherin in mediating intracellular localization of the hybrid carrier was verified by blocking integrin binding site with excess free fibronectin and up-regulating both integrin and E-cadherin through PKC activation. Thus, the new establishment of a bio-functional hybrid gene-carrier would promote and facilitate development of stem cell-based therapy in regenerative medicine. [Copyright &y& Elsevier]

Some strains of lactobacilli can stimulate macrophages and dendritic cells to secrete IL-12, which plays a key role in activating innate immunity. We examined the IL-12-inducing ability of 47 Lactobacillus strains belonging to 10 species in mouse peritoneal macrophages, and characterized the properties important for the induction of IL-12. Although considerable differences in IL-12-inducing ability were observed among the strains tested, ahnost all strains belonging to the Lactobacillus casei group (L. casei, Lactobacillus rhamnosus, and Lactobacillus zeae) or to Lactobacillus fermentum induced high levels of IL-12. Phagocytosis of lactobacilli was necessary for IL-12 induction, and the strains with strong IL-12 induction were relatively resistant to lysis in the macrophages. The sensitivity of Lactobacillus strains to in vitro treatment with M-1 enzyme, a member of the N-acetyhnuramidases, was negatively correlated with IL-12-inducing ability. Using a probiotic strain, L. casei strain Shirota (LcS), we showed that the cell wall of LcS could be digested by long-term treatment with a high dose of M-1 enzyme and that the IL-12-inducing ability was diminished according to the duration of the enzyme treatment. The soluble polysaccharide-peptidoglycan complex released from the cell wall of LcS did not induce IL-12, whereas the insoluble intact cell wall of LcS induced IL-12. These results suggest that the intact cell wall structure of lactobacilli is an important element in the ability to induce IL-12 and that Lactobacillus strains having a rigid cell wall resistant to intracellular digestion effectively stimulate macrophages to induce IL-12. [ABSTRACT FROM AUTHOR]

Abstract: Molecular dynamics simulations of N-terminal peptides from apo-myoglobin with several lengths were executed to study their stability to testify the possibility of cotranslational folding. By analyzing 10ns MD simulations in water, we found that the secondary and tertiary structures of a short N-terminal peptide (36 residues) are unstable whereas those of longer N-terminal peptides (more than 77 residues) are relatively stable. In addition, we confirmed that the structural changes are driven by the free energy. Our results suggest that a nascent apo-myoglobin chain starts to form α-helix structures after elongation of at least 77 amino acid residues. [Copyright &y& Elsevier]

We studied the stereoselective propylene polymerization catalyzed by the ion pair (IP) active species of (pyridylamido)hafnium(IV) complex, the catalyst. In particular, we focused on the role of the counteranion (CA) for the reaction mechanism of propylene insertion because it had never been investigated from the molecular point of view. First, we searched for a variety of IP configurations by the molecular dynamics (MD) method and quantum chemical calculation, and located the transition states (TSs) of propylene insertion. By comparing the CA-bound catalysts with the isolated ones, it was revealed that the manner of energetically favorable insertion is interestingly altered due to the location of the CA. Next, we showed that the CA is essential to determine the coordination structures of the Hf atom at transition state. Therefore, it was concluded that the role of the CA is critical to accurately control the polymerization mechanism. Finally, we proposed a synthesis experiment which would be advantageous to increase the stereoselectivity of the catalyst on the basis of the present polymerization mechanism. [ABSTRACT FROM AUTHOR]

Interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) signals play key roles in the pathogenesis of inflammatory bowel disease (IBD). We previously described that both intact cells and a cell wall-derived polysaccharide–peptidoglycan complex (PSPG) in a strain of lactobacillus [ Lactobacillus casei Shirota (LcS)] inhibited IL-6 production in lipopolysaccharide (LPS)-stimulated lamina propria mononuclear cells (LPMCs) isolated from murine IBD. Diets with LcS improve murine IBD by suppression of IL-6 synthesis in LPMCs. Moreover, LcS supplementation with fermented milk ameliorates disease activity in patients with active ulcerative colitis. Here, we focused on the specific roles of PSPG in LcS concerning their anti-inflammatory actions. PSPG derived from LcS, and no other strain of lactobacilli, inhibited IL-6 production in LPS-stimulated murine IBD LPMCs. Purified PSPG-I from LcS inhibited IL-6 synthesis in LPS-stimulated murine IBD LPMCs through the inhibition of nuclear factor-κB. The anti-IL-6 action of LcS PSPG was abrogated by masking with monoclonal anti-PSPG-I. Furthermore, PSPG-I-negative L. casei strains (PSPG-I-negative mutant LcS: LCΔPSPG-I, L. casei ATCC 334) did not inhibit IL-6 production. Finally, we confirmed the effects of PSPG-I on LcS in the models of both IBD and colitis-associated cancer (CAC). In the IBD model, ingestion of LcS improved ileitis and inhibited activation of IL-6/STAT3 signaling, while ingestion of the LCΔPSPG-I strain did not. In the CAC model, treatment with LcS, but not the LCΔPSPG-I strain, showed tumour-suppressive effects with an inhibition of IL-6 production in the colonic mucosa. These results suggested that a specific polysaccharide component in an L. casei strain plays a crucial role in its anti-inflammatory actions in chronic intestinal inflammatory disorders. [ABSTRACT FROM AUTHOR]

The interstitial nucleus of Cajal (INC) is thought to play an important role in torsional/vertical eye position and head posture, and disorders of the INC induce abnormal ocular movements and head tilt. Our patients with ocular tilt reactions simultaneously also had disturbances in ambulatory balance, yet no reports address the loss of balance control induced by disorders of the INC. We examined the ambulatory disturbances induced by INC lesion. We experienced three patients with ocular movement disorders and abnormal head tilt due to thalamic infarction. We performed ophthalmic examinations on and checked the balance of them. With funduscopy, abnormal cycloduction was seen in the unaffected side and normal cycloduction was observed in the affected side. Nevertheless, Hess charts showed distortions in the visual image of both eyes. They all had disorders of balance control. We tried to treat them using the Bobath approach for improving their ambulatory balance. With subsequent improvements in balance control it was possible for them to take short walks, but it was difficult to make any improvements in their ocular movement. The INC is related to balance control of ambulation and disorders of the INC induce ambulatory disturbances. Cycloduction was only observed in the unaffected side, but Hess charts showed distortions of the visual image in both eyes. Ambulation was briefly improved, but diplopia persisted in these patients. [ABSTRACT FROM AUTHOR]

Abstract: Two unique and fascinating properties of carbonate apatite which are well-known in hard tissue engineering, have been unveiled, for the first time, for the development of the simplest, but most efficient non-viral gene delivery device — ability of preventing the growth of crystals needed for high frequency DNA transfer across a plasma membrane and a fast dissolution rate for effective release of DNA during endosomal acidification, leading to a remarkably high transgene expression (5 to 100-fold) in mammalian cells compared to the widely used transfecting agents. Moreover, by modulating the crystal dissolution rate of carbonate apatite through incorporation of fluoride or strontium into it, transfection activity could be dramatically controlled, thus shedding light on a new barrier in the non-viral route, which was overlooked so far. Thus we have developed an innovative technology with significant insights, that would come as a promising tool for both basic research laboratories and clinical settings. [Copyright &y& Elsevier]

IL-6/STAT-3 signals play key roles in inflammatory bowel disease (IBD). It is known thatLactobacillus caseistrain Shirota (LcS) improves inflammatory disorders. This study aimed to elucidate the effect of LcS on murine chronic IBD and to clarify the mechanism. We focused the inhibitory effect of LcS on the production of IL-6 in lipopolysaccharide (LPS)-stimulated large intestinal lamina propria mononuclear cells (LI-LPMC) isolated from mice with chronic colitis and in RAW264·7 cellsin vitro. We also determinedin vivothe effect of LcS on murine chronic IBD models induced with dextran sodium sulphate and SAMP1/Yit mice. Finally, we examined the cellular determinants of LcS for the down-regulation of IL-6 secretion by LI-LPMC, RAW264·7 cells and peripheral blood mononuclear cells (PBMC) derived from patients with ulcerative colitis (UC). LcS, but not other strains ofLactobacillus, inhibited the production of IL-6 in LPS-stimulated LI-LPMC and RAW264·7 cells, down-regulating the nuclear translocation of NF-κB. The LcS-diet-improved murine chronic colitis is associated with the reduction of IL-6 synthesis by LI-LPMC. LcS also improved chronic ileitis in SAMP1/Yit mice. The release of IL-6in vitroin LPS-stimulated LI-LPMC, RAW 264·7 cells and UC-PBMC was inhibited by a polysaccharide-peptidoglycan complex (PSPG) derived from LcS. This probiotic-induced improvement in murine chronic inflammatory bowel disease is associated with the down-regulation of pro-inflammatory cytokines such as IL-6 and IFN-γ production in LPMC. Therefore, LcS may be a useful probiotic for the treatment of human inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the comparison between endoscopic and conventional injection in aluminum potassium tannic acid (ALTA) in sclerotherapy.

Our study, conducted between April 2022 and January 2024, was aimed at clarifying components of the rest-activity rhythm (RAR) involved in improvement of social frailty state before or after a 3-month multi-component exercise intervention in the elderly. Participants were recruited from the general population in Akita prefecture, Japan. We administered a four-item social frailty screening questionnaire to classify the severity of social frailty in each participant before and after the 3-month intervention. The RAR parameters were measured on an Actiwatch Spectrum Plus device worn by the subjects for 7 continuous days. As the final sample, 65 participants classified into the improved/maintained group ( n  = 36) or the deteriorated group ( n  = 29) according to the change in the social frailty classification after the intervention were included in the analysis. The results of a binomial logistic regression analysis showed significantly higher values of interdaily stability (IS) and usual walking speed at the post-test after the intervention. Based on our findings, we propose that stability of the rest-activity rhythm related to synchronization with external stimuli (such as social effect and physical activity) might have clinical impact on improvement of social frailty state in elderly community-dwellers.

This study presents a pioneering report on an endoscopic assisted total maxillectomy that allows for en bloc resection without a facial skin incision. Laryngoscope, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

In this study, novel phosphorescent dipyrido[3,2- a ;2'3'- c ]phenazine (dppz)-platinum(II)-phenylacetylide complexes were developed to fabricate non-doped organic light-emitting diodes (OLED) by solution-processing. To facilitate the charge carrier injection into the emitting layer (EML), 3,6-di- tert -butylcarbazole-functinalized phenylacetylides were employed. As for the dppz ligand, 9,9-dihexylfluoren-2-yl and 4-hexylthiophen-2-yl side-arms were introduced to the 2,7-positions, which led to reddish orange and red photoluminescence (PL), respectively, in solution and film states (PL wavelength: ca. 600 and ca. 625 nm, respectively). The carbazole-appended phenylacetylide ligands hardly affected the emission color, although unsubstituted phenylacetylides gave rise to aggregate- or excimer-based near-infrared PL with a low quantum yield. Two types of non-doped OLEDs were fabricated: single-layer and multilayer devices. In both devices, the organic layers were fabricated by spin-coating, and the EML consisted of a neat film of the corresponding platinum(II) complex. Therein, electroluminescence spectra corresponding to those of PL were observed. The single-layer devices exhibited low device efficiencies due to a deteriorated charge carrier balance. The multilayer devices possessed hole- and electron-transporting layers on the anode and cathode sides of the EML, respectively. Owing to an improved charge carrier balance, the multilayer devices exhibited higher device performance, affording considerably improved values of luminance and external quantum efficiency.

Objectives: This study aimed to evaluate the prognostic value of magnetic resonance imaging (MRI) findings in predicting local recurrence in patients with maxillary sinus cancer treated with super-selective intra-arterial infusion of high-dose cisplatin with concomitant radiotherapy (RADPLAT)., Methods: This single-center retrospective study included consecutive patients with maxillary sinus squamous cell carcinoma, who underwent RADPLAT between October 2016 and September 2021. MRI was performed before (within 2 weeks) and 1 month after (post-treatment MRI) the start of treatment. Tumor reduction rates and pre-treatment cross-sectional areas were calculated from the maximum cross-sectional areas on pre- and post-treatment MRI T2-weighted axial images. Statistical analyses, including receiver operating characteristic analysis, were performed to assess the predictive value of the tumor reduction rates., Results: Twenty-four patients were included in this study. Recurrence occurred in seven patients with a median time of 213 days. The tumor reduction rates were significantly higher in the benign post-treatment changes group compared to the recurrence group (median, 0.814 vs. 0.174; p < 0.001). The cut-off value for the reduction rate between the groups was 0.3578. No significant difference was observed in the maximum pre-treatment cross-sectional area between the groups (p = 0.664). The inter-observer agreement for the tumor areas was excellent., Conclusions: The tumor reduction rate calculated from MRI T2-weighted images may be a predictor of local recurrence in patients with maxillary sinus cancer treated with RADPLAT. Patients with lower reduction rates may benefit from early salvage surgeries., Competing Interests: Declaration of competing interest The authors have no funding, financial relationships, or conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Competing Interests: The authors have no conflicts of interest to declare.

Background: Information regarding the status of surgical antimicrobial prophylaxis (SAP) in Japanese hospitals is lacking. This study aimed to explore the status of SAP prescriptions for surgeries and adherence to Japanese SAP guidelines., Methods: From February to July 2020, a 1-day multicentre point prevalent survey was conducted at 27 hospitals in Aichi Prefecture, Japan. Patients prescribed SAP were included in this study. The appropriateness of the SAP was evaluated based on the guidelines for selection of antimicrobials and their duration. Surgery was defined as appropriate when all the items were appropriate., Results: A total of 728 patients (7.1 %; 728/10,199) received antimicrobials for SAP. Among them, 557 patients (76.5 %, 557/728) underwent the surgeries described in the guidelines. The overall appropriateness of all surgeries was 33.9 % (189/557). The appropriate selection of antimicrobial before/during and after surgery and their durations were 67.5 % (376/557), 67.5 % (376/557), and 43.3 % (241/557), respectively. The overall appropriateness ranged from 0 % (0/37, oral and maxillofacial surgery) to 58.7 % (88/150, orthopaedic surgery) and 27.7 % (36/130, community hospitals with 400-599 beds) to 47.2 % (17/36, specific hospitals). Cefazolin was the most prevalent antimicrobial prescribed before/during (55.5 %, 299/539), and after (45.1 %, 249/552) surgery. In total, 101 oral antimicrobials were prescribed postoperatively., Conclusions: SAP adherence by specific surgical fields and hospitals was shown in this study. Intensive intervention and repeated surveillance are necessary to improve SAP prescriptions in Japanese hospitals., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest relevant to this article., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Objectives: Acute kidney injury (AKI) represents a major toxicity associated with cisplatin. We developed a risk prediction model for cisplatin-induced AKI in patients with postoperative high-risk head and neck cancer who received chemoradiotherapy during a randomized phase II/III trial, JCOG1008., Materials and Methods: Two hundred and fifty-one patients received radiotherapy with weekly cisplatin at 40 mg/m 2 (weekly arm) or 3-weekly cisplatin at 100 mg/m 2 (3-weekly arm). AKI was defined using the AKI Network classification/staging system as increased serum creatinine of ≥0.3 mg/dL or a ≥1.5-fold increase from baseline 30 days after completing chemoradiotherapy. The Akaike information criterion was used to explore the optimal model by combining explanatory variables at registration., Results: Among the 251 patients (210 men and 41 women (median age; 62 years)), 94 (37.5 %) developed cisplatin-induced AKI. The optimal cisplatin-induced AKI risk prediction model comprised four factors, including a primary site of hypopharynx/larynx (vs. oral cavity/oropharynx), 3-weekly arm (vs. weekly arm), serum albumin of ≤3.5 g/dL (vs. >3.5 g/dL) and creatinine clearance (CCr) of <90 mL/min (vs. ≥90 mL/min). The incidence of cisplatin-induced AKI rose with cumulative count of the four factors. When the cumulative count was ≥2, the positive predictive value for cisplatin-induced AKI was 50.3 %., Conclusions: We developed a risk prediction model for cisplatin-induced AKI in patients with head and neck cancer who received postoperative chemoradiotherapy using primary site, cisplatin administration method, serum albumin, and CCr. Patients with risk factors unrelated to the cisplatin administration method should adopt a weekly cisplatin regimen., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yoshinori Imamura Speakers' Bureau - Daiichi Sankyo/UCB Japan; MSD Naomi Kiyota Honoraria - AstraZeneca; Bayer; Bristol-Myers Squibb Japan; Eisai; Lilly Japan; Merck Serono; MSD; Ono Pharmaceutical Consulting or Advisory Role - Adlai Nortye; Ono Pharmaceutical; Shift Zero Research Funding - Adlai Nortye (Inst); Bayer (Inst); Boehringer Ingelheim (Inst); Bristol-Myers Squibb (Inst); Lilly (Inst); Ono Pharmaceutical (Inst); Rakuten Medical (Inst) Makoto Tahara Honoraria - Bayer; Bristol-Myers Squibb; Eisai; Lilly; Merck Serono; MSD; Ono Pharmaceutical Consulting or Advisory Role - Astellas Pharma; Bayer; Boehringer Ingelheim; Bristol-Myers Squibb; Eisai; Genmab; Janssen; Lilly; MSD; Nanobiotix; Nektar; Ono Pharmaceutical; Pfizer; Rakuten Medical Research Funding - AstraZeneca (Inst); Bayer (Inst); Bristol-Myers Squibb (Inst); GlaxoSmithKline (Inst); Lilly (Inst); Merck Serono (Inst); Merck Sharp & Dohme (Inst); Novartis (Inst); Ono Pharmaceutical (Inst); Pfizer (Inst); Rakuten Medical (Inst) Takeshi Kodaira Speakers' Bureau - Accuray; AstraZeneca; Bristol-Myers Squibb; Chugai Pharma; Hitachi; Janssen; Merck Serono; Ono Pharmaceutical; Reason Why Co. Ryuichi Hayashi Consulting or Advisory Role - Rakuten Medical Japan Research Funding - Japan Agency for Medical Research and Development Hiroshi Nishino No Relationships to Disclose Yukinori Asada No Relationships to Disclose Hiroki Mitani No Relationships to Disclose Shigemichi Iwae Consulting or Advisory Role - Merck (Inst) Speakers' Bureau - Bristol-Myers Squibb Japan; Merck; MSD; Ono Pharmaceutical Research Funding - Ascent Development Services (Inst); GlaxoSmithKline (Inst); Merck (Inst); MSD (Inst); Ono Pharmaceutical (Inst) Nobuhiro Hanai Honoraria - Bristol-Meyers Squibb; Covidien; Eisai; Merck; MSD K.K; Ono Pharmaceutical; Rakuten Medical Research Funding - MSD K.K Hiroki Hara Honoraria - Asahi Kasei; Bayer; Bristol-Myers Squibb; Chugai Pharma; Daiichi Sankyo/UCB Japan; Lilly; Merck Serono; MSD; Ono Pharmaceutical; Taiho Pharmaceutical; Takeda; Yakult Honsha Consulting or Advisory Role - Boehringer Ingelheim; Bristol-Myers Squibb Japan; Chugai Pharma; MSD; Ono Pharmaceutical Research Funding - ALX Oncology (Inst); Amgen (Inst); Astellas Pharma (Inst); AstraZeneca (Inst); Bayer (Inst); BeiGene (Inst); Boehringer Ingelheim (Inst); Bristol-Myers Squibb Japan (Inst); Chugai Pharma (Inst); Daiichi Sankyo (Inst); Dainippon Sumitomo Pharma (Inst); Eisai (Inst); Janssen Oncology (Inst); Merck Serono (Inst); MSD (Inst); Ono Pharmaceutical (Inst); Taiho Pharmaceutical (Inst) Akihiro Homma Speakers' Bureau - Bayer Yakuhin; Bristol-Myers Squibb; Demant; Eisai; Kyorin; Lilly Japan; Meiji Seika Kaisha; Merck; Mitsubishi Tanabe Pharma; MSD K.K; Ono Pharmaceutical; Rakuten Medical Japan; Sanofi; Taiho Pharmaceutical Research Funding - Eisai; Iwasaki Denshi; Kyorin; Mitsubishi Tanabe Pharma; Ono Pharmaceutical; Otsuka; Taiho Pharmaceutical; Torii Pharmaceutical Others had no relationships to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background and Purpose: Hypothyroidism is a recognized late adverse event following radiotherapy for head and neck cancer (HNC). In the JCOG1008 trial, we treated patients with high-risk HNC with postoperative chemoradiotherapy. We aimed to elucidate factors associated with hypothyroidism by analyzing the JCOG1008 data., Materials and Methods: In 2012-2018, 261 patients from 28 institutions were enrolled in JCOG1008. Thyroid function tests were conducted to assess hypothyroidism, including free thyroxine (FT4) and thyroid-stimulating hormone assays. Hypothyroidism was defined as Grade 2 or higher in CTCAE v4.0. Various clinical and dosimetric parameters were analyzed. In radiotherapy, there were no dose constraints for the thyroid. Multivariable analysis was conducted on these variables to identify predictive factors for hypothyroidism., Results: The analysis included 162 patients (57 with 3D-CRT and 105 with IMRT), with a median follow-up of 4.7 years (0.3-9.3 years). Among these, 27 (16.7 %) developed hypothyroidism within 2 years after radiotherapy. In a multivariable analysis, the weekly cisplatin [OR=7.700 (CI: 1.632-36.343, p = 0.010)] and baseline FT4 [OR=0.009 (CI: <0.001-0.313, p = 0.010)] were significantly associated with hypothyroidism in the IMRT group. Regarding dosimetric characteristics, V 60Gy [OR=1.069 (CI: 0.999-1.143, p = 0.054)] was potentially associated with the development of hypothyroidism., Conclusion: The study revealed that the incidence of hypothyroidism within 2 years after postoperative chemoradiotherapy for high-risk HNC was 16.7 % based on analytical results from prospective clinical trials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The microscopic effects of each substituent of the Hf catalyst and the growing polymer on the monomer insertion process were investigated for Hf-pyridyl amido-catalyzed coordinative chain transfer polymerization using the Red Moon method. Since the Hf catalyst has two reaction sites, cis - and trans -sites, we separately applied the appropriate analysis methods to each one, revealing that the naphthalene ring influenced monomer insertion at the cis -one, while the i -Pr group and the hexyl group of the adjacent 1-octene unit did the trans -one. It was interesting to find that the hexyl group of the 1-octene-inserted catalyst (oHfCat) pushes the naphthalene ring toward the cis -site and narrows the space at the cis -site, thus indirectly creating a steric hindrance to cis -insertions. Further, the relative position of the Hf catalyst and the growing polymer was found to be strongly influenced by the patterns of insertion reactions, i.e., cis - or trans -insertions. In particular, it was clarified that, after trans -insertions, the growing polymer on the Hf atom covers the cis -site, making cis -insertion less likely to occur. These studies reveal the microscopic effects of the catalyst substituents and the growing polymer on the catalyst during the polymerization reaction process; these microscopic analyses using the RM method should provide atomistic insights that are not easy to obtain experimentally for advanced catalyst design and polymerization control.