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Wen Jun Zhang,* Chong Ling Hu,* Bing Ling Guo, Xi Ping Liang, Chao Yu Wang, Tao Yang Department of Hematology Oncology, Chongqing University Cancer Hospital, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tao Yang, Department of Hematology Oncology, Chongqing University Cancer Hospital, No. 181, Hanyu Road, Shapingba District, Chongqing, 400030, People’s Republic of China, Tel +86-13527363925, Email ppyangtao@163.comObjective: The purpose of this study was to analyze the mechanism by which STAT5B inhibits ferroptosis in mantle cell lymphoma (MCL) by promoting DCAF13 transcriptional regulation of p53/xCT pathway.Methods: The correlations between STAT5B, DCAF13 and ferroptosis in MCL were analyzed using Gene Expression Profiling Interactive Analysis (GEPIA, http://gepia.cancer-pku.cn/index.html). The expression levels and pairwise correlations of STAT5B, DCAF13, p53 and xCT in MCL patients were detected, respectively. STAT5B was silenced to confirm their criticality in MCL ferroptosis. the effects of blocking necrosis, apoptosis and ferroptosis on the anti-MCL effects of STAT5B were examined. Cells with STAT5B overexpression and/or DCAF13 silencing were constructed to confirm the involvement of DCAF13 in the STAT5B-regulated p53/xCT pathway. The regulation of p53 ubiquitination was confirmed by DCAF13 overexpression and MG132. The effects of silencing DCAF13 and MG132 on STAT5B overexpression on MCL was clarified by a tumor-bearing nude mouse model.Results: DCAF13 was overexpressed in MCL and positively correlated with STAT5B, negatively correlated with p53, and positively correlated with xCT. Inhibition of ferroptosis alleviated the inhibitory effects of siSTAT5B on MCL, while inhibition of necrosis and apoptosis had few effects. Silencing of DCAF13 led to the blocking of STAT5B regulation of p53/xCT and ferroptosis. The changes in DCAF13 and the addition of MG132 did not have statistically significant effects on p53 mRNA. Elevation of DCAF13 resulted in downregulation of p53 protein levels, and this inhibition was reversed by MG132. In animal models, the promotion of MCL and the inhibition of ferroptosis by STAT5B. Silencing of DCAF13 blocked STAT5B inhibition of p53 and induction of xCT, GPX4, and GSH.Conclusion: STAT5B suppresses ferroptosis by promoting DCAF13 transcription to regulate p53/xCT pathway to promote MCL progression.Keywords: mantle cell lymphoma, STAT5B, DCAF13, ferroptosis

Guo-Tian Ruan,1– 3,&ast; Ming Yang,1– 3,&ast; Xiao-Wei Zhang,1– 3,&ast; Meng-Meng Song,1– 3 Chun-Lei Hu,1– 3 Yi-Zhong Ge,1– 3 Hai-Lun Xie,1– 3 Tong Liu,1– 3 Meng Tang,1– 3 Qi Zhang,1– 3 Xi Zhang,1– 3 Kang-Ping Zhang,1– 3 Xiang-Rui Li,1– 3 Qin-Qin Li,1– 3 Yong-Bing Chen,1– 3 Kai-Ying Yu,1– 3 Ming-Hua Cong,4 Kun-Hua Wang,5 Han-Ping Shi1– 3 1Department of Gastrointestinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of China; 2Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of China; 3Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, 100038, People’s Republic of China; 4Comprehensive Oncology Department, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100038, People’s Republic of China; 5Department of Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, 650000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Han-Ping ShiDepartment of Gastrointestinal Surgery and Beijing Shijitan Hospital, Capital Medical University, 10 Tie Yi Road, Beijing, 100038, People’s Republic of ChinaTel +86-10- 6392 6985Fax +86-10 -6392 6325Email shihp@ccmu.edu.cnBackground: Systemic inflammation and cachexia are associated with adverse clinical outcomes in elderly patients with cancer. The survival outcomes of elderly patients with cancer cachexia (EPCC) with high inflammation and a high risk of mortality are unknown. This study aimed to investigate the impact of high inflammation on the prognosis of EPCC patients with high mortality.Patients and Methods: This multicenter cohort study included 746 EPCC (age > 65 years) with a mean age of 72.00 ± 5.24 years, of whom 489 (65.5%) were male. The cut-off value for the inflammation index was obtained using the optimal survival curve. The different inflammatory indicators were assessed using the concordance index (C-index), decision curve analysis (DCA), and prognostic receiver operating characteristic (ROC). The high mortality risk group of EPCC was defined by the 2011 Fearon Cancer Diagnostic Consensus. EPCC were divided into the high-risk group, which satisfies three diagnostic criteria, and a low-risk group, which satisfies only one or two diagnostic criteria.Results: The C-index, DCA, and prognostic ROC indicated the superiority of advanced lung cancer inflammation index (ALI) compared with other indicators, including neutrophil–lymphocyte ratio (NLR), prognostic nutritional index (PNI), systemic immune-inflammation index (SII), and platelet–lymphocyte ratio (PLR). Whether ALI was used as a continuous or a categorical variable, ALI had a better prognostic value in EPCC compared with other inflammatory indicators. In particular, patients with low ALI (< 25.03) had a worse overall survival (OS) than patients with high ALI (≥ 25.03) (P < 0.001, HR [95% CI] = 2.092 [1.590– 2.751]). The combination effect analysis showed that the risk of mortality of the patients in the low-ALI and high-risk groups was 3.095-fold higher than that of patients in the high-ALI and low-risk groups.Conclusion: The prognostic and discriminative value of the inflammatory indicator ALI was better than that of NLR, PNI, SII, and PLR in EPCC. The high-risk group of EPCC with a low ALI would increase the death risk of OS.Keywords: ALI, systemic inflammation, cancer cachexia, elderly, overall survival

Kaida Jiang,1 Lingjiang Li,2 Xueyi Wang,3 Maosheng Fang,4 Jianfei Shi,5 Qiuyun Cao,6 Jincai He,7 Jinan Wang,8 Weihao Tan,8 Cuili Hu8 1Psychiatry Department, Shanghai Mental Health Center, Shanghai, 2Psychiatry Department,The Second Xiangya Hospital, Central South University, Changsha, 3Psychiatry Department, First affiliated Hospital of Hebei Medical University, Shijiazhuang, 4Psychiatry Department, Wuhan Mental Health Center, Wuhan, 5Psychiatry Department, Hangzhou the 7th Hospital, Hangzhou, 6Psychology Department, Nanjing Drum Tower Hospital, Nanjing, 7Neurology Department, First affiliated Hospital of Wenzhou Medical University, Wenzhou, 8Medical Affairs Department, Xi’an Janssen Pharmaceutical Ltd., Beijing, People’s Republic of China Background: Significant anxiety symptoms are associated with poor clinical course and outcome in major depressive disorder (MDD). This single-arm, open-label study aimed to evaluate the efficacy and tolerability of escitalopram treatment in patients with MDD and anxiety symptoms. Methods: Adult patients with MDD and anxiety symptoms (Montgomery–Asberg Depression Rating Scale [MADRS] ≥22 and Hamilton Anxiety Rating Scale [HAM-A] ≥14) were enrolled and received escitalopram (10–20 mg/day) treatment for 24 weeks. Symptom status was assessed by MADRS, 17-item-Hamilton Depression Rating Scale, HAM-A, and Clinical Global Impression Scale at baseline and the following visits. Quality of life was assessed by Short Form-12, and safety was evaluated by adverse events, laboratory investigations, vital signs, and physical findings. Results: Overall, 200 of 318 (66.2%) enrolled patients completed the 24-week treatment. The remission (MADRS ≤10 and HAM-A ≤7) rate in the full analysis set (N=285) was 73.3% (95% confidence interval: 67.80, 78.38) at week 24. Mean (± standard deviation) MADRS total score was 33.4 (±7.13) and HAM-A score was 27.6 (±7.26) at baseline, which reduced to 6.6 (±10.18) and 6.0 (±8.39), respectively, at week 24. Patients with higher baseline depression and anxiety level took longer to achieve similar remission rates. Overall, 80 of the 302 (26.5%) patients included in the safety set reported at least 1 treatment-emergent adverse event (TEAE). Most frequently reported TEAEs (>2%) were headache (4.0%), nasopharyngitis (3.6%), nausea (3.0%), and dizziness (2.6%). Serious TEAEs were reported by 1.3% patients; no deaths were reported. Conclusion: Escitalopram 10–20 mg/day was effective and well-tolerated in the long-term treatment of MDD with anxiety symptoms in adult Chinese population. Keywords: anxiety, Chinese, escitalopram, long term, major depressive disorder

Chih-Ling Hu, Kai-Ling Peng Department of Ophthalmology, Chi Mei Medical Center, Tainan, Taiwan Purpose: We report a rare case of silicone oil droplets adhering to the posterior surface of an intraocular lens (IOL) after removal of silicone oil for a patient with retinal reattachment, who had a history of pseudophakic rhegmatogenous retinal detachment. Case report: A 45-year-old male with a history of cataract surgeries of both eyes developed pseudophakic retinal detachment in his left eye. He received surgeries of scleral buckle and standard 3-port pars plana vitrectomy with silicon oil tamponade. With retinal attachment for 7 months, he underwent removal of silicone oil in the left eye. However, a big silicone oil droplet was found on the posterior surface of the IOL with complaints of distorted micropsia and poor vision, a month later. Pars plana vitrectomy using a 20-gauge vitreous cutter, which was supposed to have a higher cleaning capability compared with a smaller size device, was performed to aspirate the main part of the big oil droplet. The residual dispersed smaller droplets at the center of the visual axis were swept peripherally using a 27-gauge bending tip cannula. Fortunately, the patient regained his vision of 20/20 without distortion and micropsia in his left eye. Conclusion: This was a rare case where silicone oil droplets were found adhering to the posterior surface of an IOL after removing silicone oil a month later. We used a 20-gauge vitrectomy system to remove large oil droplets and swept smaller ones off the visual axis to improve the vision and visual quality. Keywords: silicone oil droplet, silicone intraocular lens, retinal detachment, retinal reattachment, 20-gauge vitreous cutter, 27-gauge bending tip cannula

Chih-Ling Hu, Kai-Ling Peng Department of Ophthalmology, Chi Mei Medical Center, Tainan, Taiwan, Republic of China Abstract: We report a rare case of bilateral macular infarction as an ocular presenting sign of systemic lupus erythematosus (SLE). A 29-year-old woman presented to our ophthalmologic clinic with a 1-week history of progressive visual loss in her left eye after she had visited a rheumatologic clinic where SLE was diagnosed. At examination, best-corrected visual acuity (BCVA) of the right eye was 6/6, and for the left was counting fingers. Fundus examination revealed perivascular hard exudates along some branches of vessels in both eyes. After pulse therapy, her BCVA in the right eye declined to 6/30 and in the left improved to 3/60. She was administered sub-Tenon’s injections of triamcinolone acetonide 50 mg/week in both eyes for 3 weeks. Her BCVA improved to 3/6 in her right eye and remained at 3/60 in her left eye. Macular infarction is an uncommon but most severe complication of SLE. Early and regular exam of the fundus in patients with SLE is necessary to avoid progression of severe ocular complications. Keywords: bilateral macular infarction, systemic lupus erythematosus

Presented here is the first reported case of natural killer (NK)/T-cell lymphoma associated with lactic acidosis (LA) and hypoglycemia. LA and hypoglycemia are rare complications of non-Hodgkin's lymphoma. A 28-year-old male patient with NK/T-cell lymphoma had a relapse after 14 mo of initial remission and was admitted to the hospital because of altered mental status. He developed severe LA (pH, 7.17; lactate, 11.2 mmol/L) and hypoglycemia (42 mg/dL) that was resistant to sodium bicarbonate and glucose infusions. A very brief partial remission was achieved after a cycle of vincristine, dexamethasone, and L-asparaginase was given, but the disease recurred quickly after chemotherapy was discontinued and the patient did not respond to additional chemotherapy. The patient expired at 47 d after relapse. An extensive review of the literature reveals that only 2 of 28 patients have achieved complete remission, and more than 75% of patients died within 1 mo. Furthermore, 90% of previously reported cases had liver involvement. The case described here indicates that non-Hodgkin's lymphoma-induced LA portends a poor prognosis. [ABSTRACT FROM AUTHOR]

Serum cardiac enzyme elevation after percutaneous coronary intervention (PCI), a relatively common complication, is a prognostic determinant of long-term outcome in patients who undergo these procedures. Statins are postulated to reduce such complications. This study investigated the short-term effects of pravastatin on serum creatine kinase myocardial isoform (CK-MB) and serum cardiac troponin I (cTpI) levels after elective PCI. Of 93 patients studied, 72 (77.4%) were men, and 21 (22.6%) were women (mean age, 58.9+/-11.0 y). Patients were randomly divided into 3 groups before they underwent elective PCI. Preoperatively, group 1 patients (n=30) received pravastatin 10 mg/d, and group 2 patients (n=29) received pravastatin 40 mg/d. Control group patients (n=34) received no lipid-lowering medication. Serum CK-MB and serum cTpI levels were measured preoperatively and then again at 6, 24, and 36 h postoperatively. Demographic features of patients and characteristics of the PCI procedure, including number of vessels/lesions and duration and number of inflations, did not differ among groups (P>.05). Mean serum CK-MB and serum cTpI levels were significantly increased after PCI in all patients (P<.001). When compared with control group patients, those given pravastatin did not experience significantly lowered postprocedural serum CK-MB or serum cTpI levels (P>.05). Preprocedural pravastatin therapy at dosages of 10 mg/d and 40 mg/d seems inadequate for preventing serum cardiac enzyme elevations during short-term follow-up after PCI. Additional research on this topic is recommended. [ABSTRACT FROM AUTHOR]

The π-conjugated [C 3 H 6+ x N 6 ] x + ( x = 0-3) cations are good functional groups, which are widely employed in the preparations of nonlinear optical (NLO) and birefringent materials due to their high hyperpolarizability and optical anisotropy. In this paper, the first melamine hydroxyborate [C 3 H 7 N 6 ] 3 [B 3 O 5 (OH) 2 ] ( MelBO-I ) was synthesized by the boric acid melting method under the molar ratio of H 3 BO 3 :C 3 H 6 N 6 = 1:1. MelBO-I ( P 2 1 / c ) exhibits a two-dimensional (2D) {[C 3 H 7 N 6 ] 3 [B 3 O 5 (OH) 2 ]} ∞ layer composed of [C 3 H 7 N 6 ] + cations and [B 3 O 5 (OH) 2 ] 3- anions interconnected via hydrogen bonds. MelBO-I exhibits significant birefringence (Δ n = 0.286@546 nm). Under the molar ratio of H 3 BO 3 /C 3 H 6 N 6 = 3:1, [C 3 H 8 N 6 ] 4 [B 12 O 19 (OH) 6 ] ( MelBO-II ) was isolated. In MelBO-II ( P 2 1 ), highly polymerized [B 12 O 19 (OH) 6 ] 8- groups form a 3D network through hydrogen bonding, featuring 1D tunnels of 8-membered and 16-membered rings filled by [C 3 H 8 N 6 ] 2+ cations. MelBO-II is the first noncentrosymmetric (NCS) bifunctional melamine borate with a moderate SHG response (0.4 × KDP) and large birefringence (Δ n = 0.285@546 nm). The results indicate that incorporating [C 3 H 6+ x N 6 ] x + ( x = 0-3) cations into borate can effectively induce birefringence. A high concentration of boric acid promotes the formation of large boric acid cluster anions and facilitates the transformation from the CS to NCS structure.

The design and synthesis of nonlinear optical (NLO) materials with a strong second harmonic generation (SHG) effect and wide band gap is a long-standing challenge because of their inverse relationship, especially for metal tellurites. We found that a lower degree of polymerization of tellurite groups corresponds to a higher proportion of non-centrosymmetric (NCS) structures formed. Based on Pauling's rule #4, introduction of cations (Al 3+ /Ga 3+ ) with higher coordination numbers and lower valence states than Te 4+ into the reaction system decreases the connectivity among tellurite groups. By regulating the reaction conditions, CS Ga(Te 3 O 7 )Br and NCS M 2 (OH)(TeO 3 )(Te 2 O 5 )X (M = Al, Ga; X = Br, Cl) were successfully synthesized, which represent the first examples of Ga/Al-tellurite-Cl/Br. The NCS compounds have presented strong SHG intensities (4.0-9.8 × KDP) and wide bandgaps (3.89-4.35 eV). And M 2 (OH)(TeO 3 )(Te 2 O 5 )X (M = Ga, Al; X = Br, Cl) are the only examples of metal tellurites with band gap exceeding 4.0 eV and SHG intensity exceeding 4 × KDP. This work provides an effective strategy for the design and synthesis of tellurite-based NLO materials with a strong SHG effect and wide bandgap., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Widening the bandgaps while maintaining a strong second harmonic generation response has always been a research hotspot in the field of nonlinear optical iodate materials. A strategy involving covalent bonding is proposed that leverages the high valent later main group cation to construct iodates with predominantly covalent interactions. By using BiO(IO 3 ) as a template, the first Sb 5+ -containing polar iodate, SbO(OH) 2 (IO 3 ) is successfully isolated. The introduction of the two hydroxide anions led to the reduction of layered BiO(IO 3 ) into 1D SbO(OH) 2 (IO 3 ) in which two corner-sharing SbO 4 (OH) 2 octahedra are further bridged by an iodate group. The covalently bonded [SbO(OH) 2 ] + chains and the optimal packing fashion of the asymmetric IO 3 - groups generate a very strong second harmonic generation signal of 14 times that of KH 2 PO 4 . Furthermore, SbO(OH) 2 (IO 3 ) exhibits a wide bandgap of 4.14 eV and a high laser induced damage threshold [27.9 × AgGaS 2 , 0.2 × KH 2 PO 4 (10 ns, 10 Hz)]., (© 2024 Wiley‐VCH GmbH.)

Balancing the critical property requirements is key to surmounting the obstacles in the application of nonlinear optical (NLO) crystals. Tricoordinated units, characterized by nearly the lowest coordination number, are common in inorganic NLO-active oxides; however, crystals solely composed of such units are rare. Herein, by assembling three distinct tricoordinated units (SbO 3 , TeO 3 , and NO 3 ) into a single crystal, a pioneering fully tricoordinated NLO material, (SbTeO 3 )(NO 3 ), was synthesized via a facile volatilization method. As the first reported tellurite-antimonite NLO crystal, (SbTeO 3 )(NO 3 ) exhibits well-balanced properties: a strong phase-matched second-harmonic generation (SHG) effect (2.2 × KDP), short UV cutoff edge (253 nm) and moderate birefringence (0.081@546 nm). Unlike most deliquescent nitrates, (SbTeO 3 )(NO 3 ) demonstrates exceptional water resistance (>30 days), attributed to its unique hydrophobic layers and stereochemically active lone pair (SCALP) electrons in the Sb 3+ and Te 4+ cations. Theoretical calculations reveal that the optical bandgap and SHG effect of (SbTeO 3 )(NO 3 ) are collectively governed by the three tricoordinated motifs, with individual SHG contributions of 20.92%, 23.88%, and 55.12% from [SbO 3 ], [TeO 3 ] and [NO 3 ], respectively. This breakthrough underscores the efficacy of the fully tricoordinated assembly strategy in engineering NLO materials with optimally balanced properties., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objective: To assess the feasibility of using non-mydriatic fundus photography in conjunction with an artificial intelligence (AI) reading platform for large-scale screening of diabetic retinopathy (DR)., Methods: In this study, we selected 120 patients with diabetes hospitalized in our institution from December 2019 to April 2021. Retinal imaging of 240 eyes was obtained using non-mydriatic fundus photography. The fundus images of these patients were divided into two groups based on different interpretation methods. In Experiment Group 1, the images were analyzed and graded for DR diagnosis using an AI reading platform. In Experiment Group 2, the images were analyzed and graded for DR diagnosis by an associate chief physician in ophthalmology, specializing in fundus diseases. Concurrently, all patients underwent the gold standard for DR diagnosis and grading-fundus fluorescein angiography (FFA)-with the outcomes serving as the Control Group. The diagnostic value of the two methods was assessed by comparing the results of Experiment Groups 1 and 2 with those of the Control Group., Results: Keeping the control group (FFA results) as the gold standard, no significant differences were observed between the two experimental groups regarding diagnostic sensitivity, specificity, false positive rate, false negative rate, positive predictive value, negative predictive value, Youden's index, Kappa value, and diagnostic accuracy (X 2 = 0.371, P > 0.05)., Conclusion: Compared with the manual reading group, the AI reading group revealed no significant differences across all diagnostic indicators, exhibiting high sensitivity and specificity, as well as a relatively high positive predictive value. Additionally, it demonstrated a high level of diagnostic consistency with the gold standard. This technology holds potential for suitability in large-scale screening of DR., Competing Interests: Declaration of competing interest All authors have contributed significantly to the manuscript and declare that the work is original and has not been submitted or published elsewhere. None of the authors have any financial disclosure or conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

In fish species, there is limited analysis of signature transcriptome profiles at the single-cell level in gonadal cells. Here, the molecular signatures of distinct ovarian cell categories in adult Nile tilapia (Oreochromis niloticus) were analysed using single-nucleus RNA sequencing (snRNA-seq). We identified four cell types (oogonia, oocytes, granulosa cell, and thecal cell) based on their specifically expressed genes and biological functions. Similarly, we found some key pathways involved in ovarian development that may affect germline-somatic interactions. A cell-to-cell communication network between the distinct cell types was constructed. We found that the bidirectional communication is mandatory for the development of germ cells and somatic cells in fish ovaries, and the granulosa cells and thecal cells play a central regulating role in the cell network in fish ovary. Additionally, we identified some novel candidate marker genes for various types of ovarian cells and also validated them using in situ hybridization. Our work reveals an ovarian atlas at the cellular and molecular levels and contributes to providing insights into oogenesis and gonad development in fish., (© 2024 Fisheries Society of the British Isles.)

Purpose: Despite its susceptibility to muscle fatigue, combined neuromuscular electrical stimulation (NMES) and blood flow restriction (BFR) are effective regimens for managing muscle atrophy when traditional resistance exercises are not feasible. This study investigated the potential of low-level laser therapy (LLLT) in reducing muscle fatigue after the application of combined NMES and BFR., Methods: Thirty-six healthy adults were divided into control and LLLT groups. The LLLT group received 60 J of 850-nm wavelength LLLT before a training program of combined NMES and BFR of the nondominant extensor carpi radialis longus (ECRL). The control group followed the same protocol but received sham laser therapy. Assessments included maximal voluntary contraction, ECRL mechanical properties, and isometric force tracking for wrist extension., Results: The LLLT group exhibited a smaller normalized difference in maximal voluntary contraction decrement (-4.01 ± 4.88%) than the control group (-23.85 ± 7.12%) ( P < 0.001). The LLLT group demonstrated a smaller decrease in muscle stiffness of the ECRL compared with the control group, characterized by the smaller normalized changes in frequency ( P = 0.002), stiffness ( P = 0.002), and relaxation measures ( P = 0.011) of mechanical oscillation waves. Unlike the control group, the LLLT group exhibited a smaller posttest increase in force fluctuations during force tracking ( P = 0.014), linked to the predominant recruitment of low-threshold MU ( P < 0.001) without fatigue-related increases in the discharge variability of high-threshold MU ( P > 0.05)., Conclusions: LLLT preexposure reduces fatigue after combined NMES and BFR, preserving force generation, muscle stiffness, and force scaling. The functional benefits are achieved through fatigue-resistant activation strategies of motor unit recruitment and rate coding., (Copyright © 2024 by the American College of Sports Medicine.)

A significant variation in chromatin accessibility is an epigenetic feature of leukemia. The cause of this variation in leukemia, however, remains elusive. Here, we identify SMARCA5, a core ATPase of the imitation switch (ISWI) chromatin remodeling complex, as being responsible for aberrant chromatin accessibility in leukemia cells. We find that SMARCA5 is required to maintain aberrant chromatin accessibility for leukemogenesis and then promotes transcriptional activation of AKR1B1, an aldo/keto reductase, by recruiting transcription co-activator DDX5 and transcription factor SP1. Higher levels of AKR1B1 are associated with a poor prognosis in leukemia patients and promote leukemogenesis by reprogramming fructose metabolism. Moreover, pharmacological inhibition of AKR1B1 has been shown to have significant therapeutic effects in leukemia mice and leukemia patient cells. Thus, our findings link the aberrant chromatin state mediated by SMARCA5 to AKR1B1-mediated endogenous fructose metabolism reprogramming and shed light on the essential role of AKR1B1 in leukemogenesis, which may provide therapeutic strategies for leukemia., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Blood-brain barrier disruption is a critical pathological event in the progression of ischemic stroke (IS). Most studies regarding the therapeutic potential of neferine (Nef) on IS have focused on neuroprotective effect. However, whether Nef attenuates BBB disruption during IS is unclear. We here used mice underwent transient middle cerebral artery occlusion (tMCAO) in vivo and bEnd.3 cells exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) injury in vitro to simulate cerebral ischemia. We showed that Nef reduced neurobehavioral dysfunction and protected brain microvascular endothelial cells and BBB integrity. Molecular docking, short interfering (Si) RNA and plasmid transfection results showed us that PGC-1α was the most binding affinity of biological activity protein for Nef. And verification experiments were showed that Nef upregulated PGC-1α expression to reduce mitochondrial oxidative stress and promote TJ proteins expression, further improves the integrity of BBB in mice. Intriguingly, our study showed that neferine is a natural PGC-1α activator and illustrated the mechanism of specific binding site. Furthermore, we have demonstrated Nef reduced mitochondria oxidative damage and ameliorates endothelial inflammation by inhibiting pyroptosis to improve BBB permeability through triggering a cascade reaction of PGC-1α via regulation of PGC-1α/NLRP3/GSDMD signaling pathway to maintain the integrity of BBB in ischemia/reperfusion injury., (© 2024. The Author(s).)

It is of great difficulty to create a new antimonite with second-harmonic-generation (SHG) intensity larger than 6 times that of KDP. In this study, a polyfluoroantimonite strategy has been proposed to explore fluoroantimonites with large nonlinear optical (NLO) coefficients. Under the cooperation of chemical (highly asymmetric π-conjugated organic amine) and physical (viscous reaction medium ethylene glycol) methods, two novel polyfluoroantimonites, namely, (3PC) 2 (Sb 4 F 14 ) and (3AP) 2 (Sb 4 F 13 ), have been achieved. Interestingly, these two structures contain two new polyfluoroantimonite groups respectively, an isolated (Sb 4 F 14 ) 2- four-member polyhedral ring and an infinite [Sb 4 F 13 ] ∞ - helical chain. More importantly, the polar (3AP) 2 (Sb 4 F 13 ) displays a strong SHG intensity of 8.1 × KDP, a large birefringence of 0.258@546 nm and a high laser-induced damage threshold (LIDT) value of 149.7 MW cm -2 . Theoretical calculations indicated that its strong SHG effect stems from the synergistic effect of the helical [Sb 4 F 13 ] ∞ - polyfluoroantimonite chain and π-conjugated 3AP + cation, with a contribution ratio of 48.93% and 50.77% respectively. This work provides a new approach for the design and synthesis of high-performance fluoroantimonites., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The development of short-wavelength nonlinear optical (NLO) materials is indispensable and urgently required for further applications. Halides have been disregarded as potential NLO materials with deep-ultraviolet (DUV) cutoff edges due to their weak second-harmonic generation (SHG) response and poor birefringence. Here, two novel and isostructural halides, KBa 3 M 2 F 14 Cl (M = Zr (KBZFC), Hf (KBHFC)), possess structures that are formed by isolated MF 7 monocapped triangular prisms and dissociative K + , Ba 2+ , and Cl - ions. Compared with reported metal halides that are transparent to the DUV region, KBZFC and KBHFC possess the strongest SHG responses (approximately 1, 0.9 × KH 2 PO 4 ), which are contributed by the synergistic effect of MF 7 (M = Zr, Hf) groups, Ba 2+ cations, and Cl - ions. The zero-dimensional structures favour sufficient birefringences (0.12, 0.10 @ 1064 nm) for phase-matchable (PM) behaviours. The discovery of KBZFC and KBHFC showcases the potential of NLO mixed metal halides transparent to the DUV region., Competing Interests: The authors declare no competing financial interests., (This journal is © The Royal Society of Chemistry.)

Birefringent crystals serve as the core elements of polarizing optical devices. However, the inherent challenge of balancing bandgap and birefringence poses a significant hurdle in designing crystals with excellent overall performance. In this study, we propose a novel approach, namely modification with perfluorinated groups, to achieve dual enhancement of the bandgap and birefringence of selenite materials. We have successfully synthesized the first selenite fluorosilicate, namely, Pb 2 (SeO 3 )(SiF 6 ). This compound exhibits a three-dimensional structure composed of two-dimensional lead selenite layers bridged by SiF 6 octahedrons. Notably, by introducing a perfluorinated SiF 6 group, the bandgap of the lead selenite compound has been expanded to 4.4 eV. Furthermore, Pb 2 (SeO 3 )(SiF 6 ) demonstrates a large birefringence (0.161 @ 546 nm), surpassing most of the selenite compounds with a bandgap larger than 4.2 eV. Theoretical calculations suggest that the large birefringence of Pb 2 (SeO 3 )(SiF 6 ) can be attributed to the synergistic effects of SeO 3 , PbO 4 and PbO 3 F 4 polyhedrons. Our research not only pioneers a new system for selenite materials, enriching the diversity of selenite structures, but also provides a design methodology for obtaining wide bandgap birefringent selenite., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

For non-centrosymmetric (NCS) oxides intended for ultraviolet (UV) nonlinear optical (NLO) applications, achieving a wide band gap, large second harmonic generation (SHG) intensity, and sufficient birefringence to satisfy phase matching is a significant challenge due to their inherent incompatibility. To address this issue, this study proposes a strategy called framework-optimized structural transformation. Building upon centrosymmetric (CS) NaGa(SeO 3 ) 2 as a foundation, an original UV selenite NLO material, NaLu(SeO 3 ) 2 , was successfully synthesized. The derived NaLu(SeO 3 ) 2 exhibits a balanced comprehensive performance, including a band gap (5.3 eV), an SHG response (2.7 × KDP), a UV cut-off edge (210 nm), a laser-induced damage threshold (LIDT) (151.69 MW cm -2 ), birefringence (Cal: 0.138@546 nm, Exp: 0.153@546 nm), thermal stability (∼575 °C) and environmental stability. Notably, its SHG effect, band gap, LIDT, and birefringence are all the largest among UV non-hydrogen pure selenite materials. Such progress can be attributed to the successful arrangement of the SeO 3 groups by optimizing the cations on the framework of the parent compound.

The first examples of alkali metal selenite sulfates, namely, Na 8 (SeO 3 )(SO 4 ) 3 (1), Na 2 (H 2 SeO 3 )(SO 4 ) (2), and K 4 (H 2 SeO 3 )(HSO 4 ) 2 (SO 4 ) (3), were successfully synthesized by hydrothermal reactions. Their structures display three different zero-dimensional configurations composed of isolated sulfate tetrahedra and selenite groups separated by alkali metals. Na 8 (SeO 3 )(SO 4 ) 3 (1) features a noncentrosymmetric structure, while Na 2 (H 2 SeO 3 )(SO 4 ) (2) and K 4 (H 2 SeO 3 )(HSO 4 ) 2 (SO 4 ) (3) are centrosymmetric. Powder second-harmonic-generation measurements revealed that Na 8 (SeO 3 )(SO 4 ) 3 (1) shows a phase-matchable SHG intensity about 1.2 times that of KDP. UV-vis-NIR diffuse reflectance spectroscopic analysis indicated that Na 8 (SeO 3 )(SO 4 ) 3 (1) has a short UV cutoff edge and a large optical band gap, which makes it a possible UV nonlinear optical material. Theoretical calculations revealed that the birefringence of Na 8 (SeO 3 )(SO 4 ) 3 (1) is 0.041 at 532 nm, which is suitable for phase-matching condition. This work provides a good experimental foundation for the exploration of new UV nonlinear crystals in an alkali metal selenite sulfate system.

The key properties of nonlinear optical (NLO) materials highly rely on the quality of functional chromophores (FCs) and their optimized interarrangement in the lattice. Despite the screening of various FCs, significant challenges persist in optimizing their arrangement within specific structures. Generally, FC alignment is achieved by designing negatively charged 2D layers or 3D frameworks, further regulated by templating cations. In this study, a novel 0D adduct NLO material, SbF 3 ·glycine, is reported. Neutrally charged 0D [SbF 3 C 2 H 5 NO 2 ] FCs, comprising [SbF 3 ] pyramids and zwitterionic glycine, are well-aligned in the structure. The alignment is facilitated by the hydrogen bonding, reinforcing a 'head-to-tail' ligation of [SbF 3 C 2 H 5 NO 2 ] FCs. Consequently, the title compound exhibits favorable NLO properties, including a large second-harmonic generation efficiency (3.6 × KDP) and suitable birefringence (cal. 0.057 @ 1064 nm). Additionally, its short absorption cut-off edge (231 nm) positions it as a promising short-wave ultraviolet NLO material. Importantly, the binary SbF 3 -amino acid system is expected to serve as a new resource for exploring ultraviolet NLO crystals, owing to the abundance of the amino acid family., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Sulfate crystals are often criticized for their low birefringence. The small anisotropic SO 4 group is becoming the biggest bottleneck hindering the application of sulfates in optical functional materials. In this study, we report a new method to significantly enhance the birefringence of sulfates. The title compound increases the birefringence recording of sulfates to 0.542@546 nm, which is significantly larger than that of the commercial birefringent crystal of TiO 2 (0.306@546.1 nm). At the infrared wavelength, the birefringence of Hg 4 (Te 2 O 5 )(SO 4 ) can be up to 0.400@1064 nm, which is also much larger than the infrared birefringent crystal of YVO 4 (0.209@1064 nm). In addition, it also has a wide transparency range, high thermal stability, and excellent environmental stability, making it a potential birefringent material. Hg 4 (Te 2 O 5 )(SO 4 ) features a novel two-dimensional layered structure composed of [Hg 4 (Te 2 O 5 )] 2+ layers separated by isolated (SO 4 ) 2- tetrahedra. This compound was designed by introducing a highly selective cation in a tellurite sulfate system. The low valence low coordination cations connect with tellurite groups only, making the sulfate isolated in the structure. The steric repulsive action of the isolated SO 4 tetrahedra may regulate the linear and lone pair groups arranged in a way that favors large birefringence. This method can be proven by theoretical calculations. PAWED studies showed that the large birefringence originated from the synergistic effect of (Hg 2 O 2 ) 2- , (Te 2 O 5 ) 2- , and (SO 4 ) 2- units, with a contribution ratio of 42.17, 37.92, and 19.88%, respectively. Our work breaks the limitation of low birefringence in sulfates and opens up new possibilities for their application as birefringent crystals.

Exploring new material systems is a highly significant task in the field of inorganic chemistry. A new mixed-valent selenium compound, Hg 3 Se(SeO 3 )(SO 4 ), was successfully synthesized through in situ reactions. This compound exhibits a novel three-dimensional structure composed of Hg 3 Se(SO 4 ) layers bridged by SeO 3 trigonal pyramids. It is the first structure containing (SeO 3 ) 2- , (SO 4 ) 2- , and Se 2- simultaneously. In addition, Hg 3 Se(SeO 3 )(SO 4 ) possesses a wide bandgap (3.5 eV), moderate birefringence (Cal:0.064@546 nm, Exp:0.069@546 nm), a high laser-induced damage threshold (23.35 MW cm -2 ), and a wide transmittance window (0.28-6.6 μm). Our work demonstrates that mixed-valent (+4, -2) selenite selenide can be potential optical materials for the mid-infrared region.

Discovering new deep ultraviolet (DUV) nonlinear optical (NLO) materials is the current research hotspot. However, how to perfectly integrate several stringent performances into a crystal is a great challenge because of the natural incompatibility among them, particularly wide band gap and large NLO coefficient. To tackle the challenge, a boron-rich closed-loop strategy is supposed, based on which a new barium borate, Ba 4 B 14 O 25 , is designed and synthesized successfully via the high-temperature solid-state melting method. It features a highly polymeric 3D geometry with the closed-loop anionic framework [B 14 O 25 ] 8- constructed by the fundamental building blocks [B 14 O 33 ] 24- . The high-density π-conjugated [BO 3 ] 3- groups and the fully closed-loop B-O-B connections make Ba 4 B 14 O 25 possess excellent NLO properties, including short UV cutoff edge (<200 nm), large second harmonic generation response (3.0 × KDP) and phase-matching capability, being a promising DUV-transparent NLO candidate material. The work provides a creative design strategy for the exploration of DUV NLO crystals., (© 2023 Wiley‐VCH GmbH.)

As the global population ages, the prevalence of neuroinflammatory diseases such as Alzheimer's disease, Parkinson's disease and stroke continues to increase. Therefore, it is necessary to develop preventive and therapeutic methods against neuroinflammatory diseases. Lipofundin is a lipid emulsion commonly used in clinical anesthetic solvents and nutritional supplements. Lipid emulsions have been shown to possess anti-inflammatory properties. However, the potential beneficial effect of lipofundin against neuroinflammation requires elucidation. In the present study, two cell models were used to investigate the efficacy of lipofundin against neuroinflammation. In the first model, BV2 mouse microglial cells were treated with lipopolysaccharide (LPS) to induce nitric oxide (NO) production as a model of neuroinflammation. In the second model, HMC3 human microglial were activated by LPS, and changes in the secretion of factors associated with inflammation were analyzed using Luminex xMAP ® technology. Griess assay results revealed that lipofundin significantly prevented and treated LPS-induced NO production. An anti-neuroinflammatory effect was also observed in HMC3 cells, where lipofundin exhibited excellent preventive and therapeutic properties by reducing the LPS-induced expression and secretion of interleukin-1β. Notably, lipofundin also promoted the secretion of certain growth factors, suggesting a potential neuroprotective effect. These results demonstrate that, in addition to its role as a solvent for drugs and nutritional support, lipofundin may also have beneficial effects in alleviating the progression of neuroinflammation. These findings may serve as an important reference for future translational medicine applications., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Chen et al.)

Introduction: Osteoarthritis (OA) is a prevalent joint disorder characterized by multifaceted pathogenesis, with macrophage dysregulation playing a critical role in perpetuating inflammation and joint degeneration., Methods: This study focuses on Songorine, derived from Aconitum soongaricum Stapf, aiming to unravel its therapeutic mechanisms in OA. Comprehensive analyses, including PCR, Western blot, and immunofluorescence, were employed to evaluate Songorine's impact on the joint microenvironment and macrophage polarization. RNA-seq analysis was conducted to unravel its anti-inflammatory mechanisms in macrophages. Metabolic alterations were explored through extracellular acidification rate monitoring, molecular docking simulations, and PCR assays. Oxygen consumption rate measurements were used to assess mitochondrial oxidative phosphorylation, and Songorine's influence on macrophage oxidative stress was evaluated through gene expression and ROS assays., Results: Songorine effectively shifted macrophage polarization from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype. Notably, Songorine induced metabolic reprogramming, inhibiting glycolysis and promoting mitochondrial oxidative phosphorylation. This metabolic shift correlated with a reduction in macrophage oxidative stress, highlighting Songorine's potential as an oxidative stress inhibitor., Discussion: In an in vivo rat model of OA, Songorine exhibited protective effects against cartilage damage and synovial inflammation, emphasizing its therapeutic potential. This comprehensive study elucidates Songorine's multifaceted impact on macrophage modulation, metabolic reprogramming, and the inflammatory microenvironment, providing a theoretical foundation for its therapeutic potential in OA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 He, Huang, Hu, Xu and Wei.)

The first examples of thioborate-thiosilicates, namely Ca 2 Ln(BS 3 )(SiS 4 ) (Ln = La, Ce, and Gd), are synthesized by rationally designed high-temperature solid-state reactions. They crystalize in the polar space group P6 3 mc and feature a novel three-dimensional crystal structure in which the discrete [BS 3 ] 3- and [SiS 4 ] 4- anionic groups are linked by Ca 2+ and Ln 3+ cations occupying the same atomic site. Remarkably, all three compounds show comprehensive properties required as promising infrared nonlinear optical materials, including phase-matchable strong second harmonic generation (SHG) responses at 2.05 µm (1.1-1.2 times that of AgGaS 2 ), high laser-induced damage thresholds (7-10 times that of AgGaS 2 ), wide light transmission range (0.45-11 µm), high thermal stabilities (>800 °C), and large calculated birefringence (0.126-0.149 @1064 nm), which justify the material design strategy of combining [BS 3 ] 3- and [SiS 4 ] 4- active units. Theoretical calculations suggest that their large SHG effects originate mainly from the synergy effects of the LnS 6 , BS 3 , and SiS 4 groups. This work not only broadens the scope of research on metal chalcogenides but also provides a new synthetic route for mixed anionic thioborates., (© 2023 Wiley-VCH GmbH.)

Background: The C-reactive protein (CRP)-triglyceride-glucose (TyG) index (CTI), which is a measure representing the level of inflammation and insulin resistance (IR), is related to poor cancer prognosis; however, the CTI has not been validated in patients with cancer cachexia. Thus, this study aimed to explore the potential clinical value of the CTI in patients with cancer cachexia., Methods: In this study, our prospective multicenter cohort included 1411 patients with cancer cachexia (mean age 59.45 ± 11.38, 63.3% male), which was a combined analysis of multiple cancer types. We randomly selected 30% of the patients for the internal test cohort (mean age 58.90 ± 11.22% 61.4% male). Additionally, we included 307 patients with cancer cachexia in the external validation cohort (mean age 61.16 ± 11, 58.5% male). Receiver operating characteristic (ROC) and calibration curves were performed to investigate the prognostic value of CTI. The prognostic value of the CTI was also investigated performing univariate and multivariate survival analyses., Results: The survival curve indicated that the CTI showed a significant prognostic value in the total, internal, and external validation cohorts. Prognostic ROC curves and calibration curves revealed that the CTI showed good consistency in predicting the survival of patients with cancer cachexia. Multivariate survival analysis showed that an elevated CTI increased the risk of death by 22% (total cohort, 95% confidence interval [CI] = 1.13-1.33), 34% (internal test cohort, 95%CI = 1.11-1.62), and 35% (external validation cohort, 95%CI = 1.14-1.59) for each increase in the standard deviation of CTI. High CTI reliably predicted shorter survival (total cohort, hazard ratio [HR] = 1.45, 95%CI = 1.22-1.71; internal test cohort, HR = 1.62, 95%CI = 1.12-2.36; external validation cohort, HR = 1.61, 95%CI = 1.15-2.26). High CTI significantly predicted shorter survival in different tumor subgroups, such as esophageal [HR = 2.11, 95%CI = 1.05-4.21] and colorectal cancer [HR = 2.29, 95%CI = 1.42-3.71]. The mediating effects analysis found that the mediating proportions of PGSGA, ECOG PS, and EORTC QLQ-C30 on the direct effects of CTI were 21.72%, 19.63%, and 11.61%, respectively We found that there was a significant positive correlation between the CTI and 90-day [HR = 2.48, 95%CI = 1.52-4.14] and 180-day mortality [HR = 1.77,95%CI = 1.24-2.55] in patients with cancer cachexia., Conclusion: The CTI can predict the short- and long-term survival of patients with cancer cachexia and provide a useful prognostic tool for clinical practice., (© 2024. The Author(s).)

Objective: To explore the correlation between periodontal health and cognitive impairment in the older population to provide the evidence for preventing cognitive impairment from the perspective of oral health care in older adults., Methods: A comprehensive search was conducted in PubMed, Embase, the Cochrane Library, the Web of Science, the China National Knowledge Infrastructure, Wanfang Data, the China Science and Technology Journal Database, and the China Biomedical Literature Database, to include both cross-sectional and longitudinal cohort studies on the association between periodontal health and cognitive impairment in older adults. The search was completed in April 2023. Following quality assessment and data organization of the included studies, meta-analysis was performed using Review Manager 5.4., Results: Twenty-two studies involving a total of 4,246,608 patients were included to comprehensively assess periodontal health from four dimensions (periodontitis, tooth loss, occlusal support, and masticatory ability), with the outcome variable of cognitive impairment (including mild cognitive impairment, Alzheimer's disease and all-cause dementia). Meta-analysis showed that, compared to those of periodontally healthy older adults, the risk of cognitive impairment in older adults with poor periodontal health, after adjusting for confounders, was significantly greater for those with periodontitis (OR=1.45, 95% CI: 1.20-1.76, P<0.001), tooth loss (OR=1.80, 95% CI: 1.50-2.15, P<0.001), compromised occlusal support (OR=1.87, 95% CI: 1.29-2.70, P=0.001), and reduced masticatory ability (OR=1.39, 95% CI: 1.11-1.75, P=0.005). The risk of cognitive impairment was higher in older adults with low-dentition than in those with high-dentition. Subgroup analysis revealed older individuals with fewer remaining teeth were at a higher risk of developing cognitive impairment compared to those with more remaining teeth, as shown by the comparison of number of teeth lost (7-17 teeth compared to 0-6 teeth) (OR=1.64, 95% CI: 1.13-2.39, P=0.01), (9-28 teeth compared to 0-8 teeth) (OR=1.13, 95% CI: 1.06-1.20, P<0.001), (19-28 teeth compared to 0-18 teeth) (OR=2.52, 95% CI: 1.32-4.80, P=0.005), and (28 teeth compared to 0-27 teeth) (OR=2.07, 95% CI: 1.54-2.77, P<0.001). In addition, tooth loss in older adults led to a significantly increased risk of mild cognitive impairment (OR=1.66, 95% CI: 1.43-1.91, P<0.001) and all-cause dementia (OR=1.35, 95% CI: 1.11-1.65, P=0.003), although the correlation between tooth loss and the risk of Alzheimer's disease was not significant (OR=3.89, 95% CI: 0.68-22.31, P=0.13)., Conclusion: Poor periodontal health, assessed across four dimensions (periodontitis, tooth loss, occlusal support, and masticatory ability), represents a significant risk factor for cognitive impairment in older adults. The more missing teeth in older adults, the higher risk of developing cognitive impairment, with edentulous individuals particularly susceptible to cognitive impairment. While a certain degree of increased risk of Alzheimer's disease was observed, no significant association was found between tooth loss and the risk of developing Alzheimer's disease. Enhancing periodontal health management and delivering high-quality oral health care services to older adults can help prevent cognitive impairment., Competing Interests: The authors declare no competing financial interest.

Background: As a prodromal stage of dementia, significant emphasis has been placed on the identification of modifiable risks of mild cognitive impairment (MCI). Research has indicated a correlation between exposure to air pollution and cognitive function in older adults. However, few studies have examined such an association among the MCI population inChina., Objective: We aimed to explore the association between air pollution exposure and MCI risk from the Hubei Memory and Aging Cohort Study., Methods: We measured four pollutants from 2015 to 2018, 3 years before the cognitive assessment of the participants. Logistic regression models were employed to calculate odds ratios (ORs) to assess the relationship between air pollutants and MCI risk., Results: Among 4,205 older participants, the adjusted ORs of MCI risk for the highest quartile of PM2.5, PM10, O3, and SO2 were 1.90 (1.39, 2.62), 1.77 (1.28, 2.47), 0.56 (0.42, 0.75), and 1.18 (0.87, 1.61) respectively, compared with the lowest quartile. Stratified analyses indicated that such associations were found in both males and females, but were more significant in older participants., Conclusions: Our findings are consistent with the growing evidence suggesting that air pollution increases the risk of mild cognitive decline, which has considerable guiding significance for early intervention of dementia in the older population. Further studies in other populations and broader geographical areas are warranted to validate these findings.

Milk production traits as the most important economic traits of dairy cows, they directly reflect the benefits of breeding and the economic benefits of pasture. In this study, A disintegrin and metalloproteinase-12 (ADAM12), Parkinson's disease gene 2 (PRKN) and dipeptidyl peptidase-like protein subtype 6 (DPP6) polymorphism in 384 Chinese Holstein cows were detected by time-of-flight mass spectrometry and through statistical analysis using software such as Popgene 32, SAS 9.4 and Origin 2022, the relationship between single nucleotide polymorphisms (SNPs) of three genes with four milk production traits such as daily milk yield (DMY), milk fat percentage (MFP), milk protein percentage (MPP) and somatic cell score (SCS) was verified at molecular level. The results showed that four polymorphic loci (116,467,133, 116,604,487, 116,618,268 and 116,835,111) of DPP6 gene, two polymorphic loci (97,665,052 and 97,159,837) of PRKN gene and two polymorphic loci (45,542,714 and 45,553,888) of ADAM12 gene were detected. PRKN-97665052, DPP6-116467133, ADAM12-45553888, DPP6-116604487 and DPP6-116835111 were all in Hardy-Weinberg equilibrium state (p > .05). ADAM12-45542714, PRKN-97159837 and PRKN-97665052 were moderately polymorphic (0.25 ≤ PIC <0.50) in Holstein. It is evident that the selection potential and genetic variation of these five loci are relatively large, and the genetic richness is relatively high. The correlation analysis of different genotypes between these eight loci and milk production traits of Holstein showed that ADAM12-45542714 and DPP6-116835111 (p < .01) had an extremely significant effects on the DMY of Chinese Holstein in Ningxia, while PRKN-97665052 had an extremely significant effect on MFP (p < .01). The effect of PRKN-97665052 and DPP6-116467133 on MPP of Holstein were extremely significant (p < .01). DPP6-116618268 had an extremely significant effect on the SCS of Holstein in Ningxia (p < .01), and AA genotype individuals showed a higher SCS than GG genotype individuals; the other two loci (ADAM12-45553888 and DPP6-116604487) had no significant effects on milk production traits of Holstein (p > .05). In addition, through the joint analysis of DPP6, PRKN and ADAM12 gene loci, it was found that the interaction effect between the three gene loci could significantly affect the DMY, SCS (p < .01) and MPP (p < .05). In conclusion, several different loci of DPP6, PRKN and ADAM12 genes can affect the milk production traits of Holstein to different degrees. PRKN, DPP6 and ADAM12 genes can be used as potential candidate genes for milk production traits of Holstein for marker-assisted selection, providing theoretical basis for breeding of Holstein., (© 2023 Wiley-VCH GmbH. Published by John Wiley & Sons Ltd.)

Myelodysplastic syndrome (MDS) is a group of clonal hematopoietic neoplasms originating from hematopoietic stem progenitor cells (HSPCs). We previously identified frequent roundabout guidance receptor 1 ( ROBO1 ) mutations in patients with MDS, while the exact role of ROBO1 in hematopoiesis remains poorly delineated. Here, we report that ROBO1 deficiency confers MDS-like disease with anemia and multilineage dysplasia in mice and predicts poor prognosis in patients with MDS. More specifically, Robo1 deficiency impairs HSPC homeostasis and disrupts HSPC pool, especially the reduction of megakaryocyte erythroid progenitors, which causes a blockage in the early stages of erythropoiesis in mice. Mechanistically, transcriptional profiling indicates that Cdc42 , a member of the Rho-guanosine triphosphatase family, acts as a downstream target gene for Robo1 in HSPCs. Overexpression of Cdc42 partially restores the self-renewal and erythropoiesis of HSPCs in Robo1 -deficient mice. Collectively, our result implicates the essential role of ROBO1 in maintaining HSPC homeostasis and erythropoiesis via CDC42 .

It has historically been exceedingly challenging to create physically and chemically stable lanthanide compounds with strong second harmonic generation (SHG) due to their strong preference to central symmetry. In this work, five new non-centrosymmetric lanthanide selenites, namely, Ln 2 F 2 (OH 2 )(MoO 3 ) 2 (SeO 3 ) 2 (Ln = Sm, Eu, Gd, Tb and Dy), are achieved by partial fluorination of the lanthanide oxygen polyhedron. An HF corrosion resistant supercritical hydrothermal method is developed, which is a facile and universal method for HF corrosion and high-temperature high-pressure environment. The title compounds displayed a novel 3D framework composed of 1D molybdenum selenite chains bridged by Ln 2 F 2 O 12 (OH 2 ) dimers. Their powder SHG responses showed a large difference, ranging from 1.0 to 9.0 × KH 2 PO 4 (KDP) at 1064 nm. The half-filled Gd compound exhibited very strong SHG efficiency of up to 1.2 × KTP (KTiOPO 4 ) at 2050 nm. Compounds Tb and Gd are the first lanthanide selenites with SHG intensity reaching KTP level, which is very rare in this system. Furthermore, these compounds can also possess excellent physicochemical stability and strong luminescence emission, indicating that they are promising multifunctional nonlinear optical materials. This work offered an effective way for design and synthesis of multifunctional and high-performant nonlinear optical materials., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Background: The development and progression of cancer cachexia are connected to systemic inflammation and physical performance. However, few relevant studies have reported the survival outcomes prediction of systemic inflammation and physical performance in patients with colorectal cancer (CRC) cachexia. This study investigated the prognostic prediction value of systemic inflammation and performance status in patients with CRC cachexia., Methods: This multicentre cohort study prospectively collected 905 patients with CRC (58.3% males, 59.3 ± 11.5 years old). Cancer cachexia was diagnosed according to the 2011 Fearon Cachexia Diagnostic Consensus. The prognostic value of systematic inflammatory indicators was determined using the area under the curve, concordance index, and multivariate survival analysis. Performance status was evaluated with Eastern Coopertive Oncology Group performance score (ECOG-PS). Survival data were analysed using univariate and multivariate Cox regression analyses., Results: The area under the curve, concordance index and survival analysis showed that C-reactive protein (CRP), lymphocyte to CRP ratio (LCR) and CRP to albumin ratio (CAR) were more stable and consistent with the survival of patients with CRC, both in non-cachexia and cachexia populations. Among patients with CRC cachexia, high inflammation [low LCR, hazard ratio (HR) 95% confidence interval (95% CI) = 3.33 (2.08-5.32); high CAR, HR (95% CI) = 2.92 (1.88-4.55); high CRP, HR (95% CI) = 3.12 (2.08-4.67)] indicated a worse prognosis, compared with non-cachexia patients [low LCR, HR (95% CI) = 2.28 (1.65-3.16); high CAR, HR (95% CI) = 2.36 (1.71-3.25); high CRP, HR (95% CI) = 2.58 (1.85-3.60)]. Similarly, among patients with CRC cachexia, high PS [ECOG-PS 2, HR (95% CI) = 1.61 (1.04-2.50); ECOG-PS 3/4, HR (95% CI) = 2.91 (1.69-5.00]) indicated a worse prognosis, compared with patients with CRC without cachexia [ECOG-PS 2, HR (95% CI) = 1.28 (0.90-1.81); ECOG-PS 3/4, HR (95% CI) = 2.41 (1.32-4.39]). Patients with CRC cachexia with an ECOG-PS score of 2 or 3-4 and a high inflammation had a shorter median survival time, compared with patients with an ECOG-PS score of 0/1 and a low inflammation., Conclusions: The systemic inflammatory markers LCR, CAR and CRP have stable prognostic values in patients with CRC. The ECOG-PS may be an independent risk factor for CRC. Combined evaluation of systemic inflammation and ECOG-PS in patients with CRC cachexia could provide a simple survival prediction., (© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Birefringent crystals can manipulate the polarization state of lasers and have vital application in polarizers, optical isolators, phase compensators, etc. The design and synthesis of crystals with large birefringence remains a challenging task. To design crystals with large birefringence, we combine an unprecedented chloroiodate(v) group (IO 2 Cl 2 ) - featuring large polarizability anisotropy and a strong stereochemically active lone pair (SCALP) with the π-conjugated 2-amino-5-chloropyridine group. The superior synergy effect of (IO 2 Cl 2 ) - and 2-amino-5-chloropyridine groups produces a new birefringent crystal, namely (C 5 H 6.16 N 2 Cl 0.84 )(IO 2 Cl 2 ). It exhibits remarkably large birefringence of 0.67 at 546 nm, far exceeding those of most visible birefringent materials reported. This work discovers the first chloroiodate(v) group and provides a new synthetic route for birefringent materials., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

An unusual O/F ordered d 0 transition metal fluoroantimonite, namely, K 2 SbMoO 2 F 7 , has been created by the cationic size effect of alkali metals. It features the largest birefringence of 0.220@550 nm among inorganic antimonites with a halogen element, which is an order of magnitude larger than the disordered A 2 SbMoO 2 F 7 (A = Rb, Cs). These three new compounds exhibit two different structures, although all of the structures were made of [SbMoO 2 F 7 ] 2- chains formed by SbF 5 square pyramids and MoO 2 F 4 octahedrons. A transparent single crystal of K 2 SbMoO 2 F 7 with dimensions of 7.0 × 5.0 × 1.0 mm 3 has been successfully grown by the aqueous solution volatilization method. The UV-vis-MIR transmission spectrum showed that K 2 SbMoO 2 F 7 can display excellent transmittance in the range of 0.5-5.0 μm and 6.0-9.8 μm, indicating its application potential as a birefringent material in the mid infrared band. This work offers a fresh approach to the design and synthesis of mid infrared birefringent materials.

Second-harmonic generation (SHG) response and birefringence are crucial properties for linear and nonlinear optical (NLO) materials, while it is difficult to further optimize these two key properties by using a single traditional functional building block (FBB) in one compound. Herein, a novel IO 4 5- unit is identified, which possesses a square-planar configuration and two stereochemically active lone-pairs (SCALPs). By combining IO 4 5- and IO 3 - units, the first examples of mixed-valent polyiodates featuring an unprecedented bowl-shaped I 5 O 12 - polymerized unit, namely (NH 4 ) 2 (I 5 O 12 )(IO 3 ) and K 1.03 (NH 4 ) 0.97 (I 5 O 12 )(IO 3 ), are successfully synthesized. Excitingly, both crystals exhibit strong SHG responses (16 × KDP and 19.5 × KDP @1064 nm) as well as giant birefringence (∆n exp  = 0.431 and 0.405 @546 nm). Detailed structure-property analyses reveal that the parallel aligned planar IO 4 5- units induce the properly aligned high-density SCALPs, leading to strong SHG response and giant birefringence for both materials. This work not only provides two new potential NLO and birefringent crystals, but also discovers a novel promising FBB (IO 4 5- ) for developing high-performance linear and nonlinear optical materials., (© 2023 Wiley-VCH GmbH.)

Two new mixed-anion cerium iodates, namely, Ce(IO 3 ) 3 F and Ce(IO 3 ) 2 (NO 3 ), have been rationally designed through the integration of hybrid anionic functional building blocks (FBBs). The structure of Ce(IO 3 ) 3 F features a novel [Ce(IO 3 ) 3 F] bilayer, and the material exhibits large birefringence (0.225 @546 nm). The structure of Ce(IO 3 ) 2 (NO 3 ) features [Ce 3 (IO 3 ) 6 ] 3+ triple layers that are further linked by planar NO 3 - units. Ce(IO 3 ) 2 (NO 3 ) shows a moderate SHG response (1 × KDP) and a high laser-induced damage threshold value (22 × AgGaS 2 ). This work demonstrates that the rich coordination geometries of cerium cations facilitate tuning of the structures of related compounds through modulating anionic FBBs.

The bone marrow microenvironment (BMM) can regulate leukemia stem cells (LSCs) via secreted factors. Increasing evidence suggests that dissecting the mechanisms by which the BMM maintains LSCs may lead to the development of effective therapies for the eradication of leukemia. Inhibitor of DNA binding 1 (ID1), a key transcriptional regulator in LSCs, previously identified by us, controls cytokine production in the BMM, but the role of ID1 in acute myeloid leukemia (AML) BMM remains obscure. Here, we report that ID1 is highly expressed in the BMM of patients with AML, especially in BM mesenchymal stem cells, and that the high expression of ID1 in the AML BMM is induced by BMP6, secreted from AML cells. Knocking out ID1 in mesenchymal cells significantly suppresses the proliferation of cocultured AML cells. Loss of Id1 in the BMM results in impaired AML progression in AML mouse models. Mechanistically, we found that Id1 deficiency significantly reduces SP1 protein levels in mesenchymal cells cocultured with AML cells. Using ID1-interactome analysis, we found that ID1 interacts with RNF4, an E3 ubiquitin ligase, and causes a decrease in SP1 ubiquitination. Disrupting the ID1-RNF4 interaction via truncation in mesenchymal cells significantly reduces SP1 protein levels and delays AML cell proliferation. We identify that the target of Sp1, Angptl7, is the primary differentially expression protein factor in Id1-deficient BM supernatant fluid to regulate AML progression in mice. Our study highlights the critical role of ID1 in the AML BMM and aids the development of therapeutic strategies for AML., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

In this study, we identify a novel class of second-order nonlinear optical (NLO) crystals, non-π-conjugated piperazine (H 10 C 4 N 2 , PIP) metal halides, represented by two centimeter-sized, noncentrosymmetric organic-inorganic metal halides (OIMHs), namely H 12 C 4 N 2 CdI 4 ( P 2 1 2 1 2 1 ) and H 11 C 4 N 2 CdI 3 ( Cc ). H 12 C 4 N 2 CdI 4 is the first to be prepared, and its structure contains a CdI 4 tetrahedron, which led to a poor NLO performance, including a weak and non-phase-matchable second harmonic generation (SHG) response of 0.5 × KH 2 PO 4 (KDP), a small birefringence of 0.047 @1064 nm and a narrow bandgap of 3.86 eV. Moreover, H 12 C 4 N 2 CdI 4 is regarded as the model compound, and we further obtain H 11 C 4 N 2 CdI 3 via the replacement of CdI 4 with a highly polarizable CdNI 3 tetrahedron, which results in a sharp enhancement of SHG response and birefringence. H 11 C 4 N 2 CdI 3 exhibits a promising NLO performance including 6 × KDP, 4.10 eV, Δ n = 0.074 @1064 nm and phase matchability, indicating that it is the first OIMH to simultaneously exhibit strong SHG response (>5 × KDP) and a wide bandgap (>4.0 eV). Our work presents a novel direction for designing high-performance NLO crystals based on organic-inorganic halides and provides important insights into the role of the hybridized tetrahedron in enhancing the SHG response and birefringence., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Organic-inorganic hybrid nonlinear optical (NLO) materials are highly anticipated because of the integration of both merits of the organic and inorganic moieties. Herein, the 2-pyrimidinone cation (C 4 H 5 N 2 O) + has been incorporated into the iodate system to form two polymorphic organic-inorganic hybrid iodates, namely, α- and β-(C 4 H 5 N 2 O)(IO 3 )·HIO 3 . They crystallize in different polar space groups ( Ia and Pca 2 1 ), and their structures feature one-dimensional (1D) chain structures composed of (C 4 H 5 N 2 O) + cations, IO 3 - anions, and HIO 3 molecules interconnected via hydrogen bonds. α- and β-(C 4 H 5 N 2 O) (IO 3 )·HIO 3 exhibit strong and moderate second-harmonic-generation (SHG) responses of 6.4 and 0.9 × KH 2 PO 4 (KDP), respectively, the same band gaps of 3.65 eV, and high powder laser-induced damage threshold (LIDT) values [51 and 57 × AgGaS 2 (AGS)]. The results of theoretical calculations revealed that the large SHG effect of α-(C 4 H 5 N 2 O)(IO 3 )·HIO 3 originated from the IO 3 and HIO 3 groups. This work indicates that (C 4 H 5 N 2 O) + is a potential group for designing new NLO materials with brilliant optical performances.

Objective: This study investigated the neuromuscular control of increasing and releasing force in patients with chronic lateral epicondylitis (CLE). Methods: Fifteen patients with CLE (10 males, 5 females, 46.5 ± 6.3 years) and fifteen healthy participants (9 males, 6 females, 45.3 ± 2.5 years) participated in this study. In addition to power grip and maximal voluntary contraction (MVC) of wrist extension, force fluctuation dynamics and characteristics of inter-spike intervals (ISI) of motor units (MUs) with various recruitment thresholds in the extensor carpi radialis brevis (ECRB) and extensor carpi radialis longus (ECRL) during a designated force-tracking task with a trapezoidal target (0%-75%-0% MVC) were assessed. Results: Besides a smaller MVC of wrist extension, the patients exhibited significantly greater task errors ( p = 0.007) and force fluctuations ( p = 0.001) during force increment than the healthy counterparts. Nevertheless, no force variables significantly differed between groups during force release ( p > 0.05). During force increment, the amplitudes of the motor unit action potential of the ECRB and ECRL muscles of the patients were smaller than those of the heathy counterparts ( p < 0.001). The patient group also exhibited a higher percentage of motor units (MU) with lower recruitment threshold (<5% MVC) in the ECRL/ECRB muscles and a lower percentage of MU with higher recruitment threshold (>40% MVC) in the ECRB muscle, compared to the healthy group. During force increment, the patient group exhibited a higher rate of decrease in inter-spike intervals (ISIs) of motor units with lower recruitment thresholds (<10% MVC) in the ECRB and ECRL muscles, compared to the control group ( p < 0.005). Conclusion: The patients with CLE exhibited more pronounced impairment in increasing force than in releasing force. This impairment in increasing force is attributed to deficits in tendon structure and degenerative changes in the larger motor units of the wrist extensors. To compensate for the neuromuscular deficits, the rate of progressive increase in discharge rate of the remaining smaller motor units (MUs) is enhanced to generate force. Significance: The deficits in neuromuscular control observed in CLE with degenerative changes cannot be fully explained by the experimental pain model, which predicts pain-related inhibition on low-threshold motor units., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Hu, Hong, Hsu, Kuan, Chen, Su, Chen and Hwang.)

Malnutrition is a common comorbidity among patients with cancer. However, no nutrition-screening tool has been recognized in this population. A quick and easy screening tool for nutrition with high sensitivity and easy-to-use is needed. Based on the previous 25 nutrition-screening tools, the Delphi method was made by the members of the Chinese Society of Nutritional Oncology to choose the most useful item from each category. According to these results, we built a nutrition-screening tool named age, intake, weight, and walking (AIWW). Malnutrition was defined based on the scored patient-generated subjective global assessment (PG-SGA). Concurrent validity was evaluated using the Kendall tau coefficient and kappa consistency between the malnutrition risks of AIWW, nutritional risk screening 2002 (NRS-2002), and malnutrition screening tool (MST). Clinical benefit was calculated by the decision curve analysis (DCA), integrated discrimination improvement (IDI), and continuous net reclassification improvement (cNRI). A total of 11,360 patients (male, n=6,024 (53.0%) were included in the final study cohort, and 6,363 patients had malnutrition based on PG-SGA. Based on AIWW, NRS-2002, and MST, 7,545, 3,469, and 1,840 patients were at risk of malnutrition, respectively. The sensitivities of AIWW, NRS-2002, and MST risks were 0.910, 0.531, and 0.285, and the specificities were 0.768, 0.946, and 0.975. The Kendall tau coefficients of AIWW, NRS-2002, and MST risks were 0.588, 0.501, and 0.326, respectively. The area under the curve of AIWW, NRS-2002, and MST risks were 0.785, 0.739, and 0.630, respectively. The IDI, cNRI, and DCA showed that AIWW is non-inferior to NRS-2002 (IDI: 0.002 (-0.009, 0.013), cNRI: -0.015 (-0.049, 0.020)). AIWW scores can also predict the survival of patients with cancer. The missed diagnosis rates of AIWW, NRS-2002, and MST were 0.09%, 49.0%, and 73.2%, respectively. AIWW showed a better nutrition-screening effect than NRS-2002 and MST for patients with cancer and could be recommended as an alternative nutrition-screening tool for this population., (© 2023. Science China Press.)

Background: Inflammation and nutritional statuses are closely related to the survival of patients with cancer. Breast cancer is the one with low level of inflammation and low risk of malnutrition. Does inflammation burden and nutrition status affect the prognosis of patients with breast cancer?, Methods: Totally 1158 patients with breast cancer from Nutrition Status and its Clinical Outcome of Common Cancers study were included, 15 nutrition-inflammation indicators (NIIs) from literatures were adopted in this study. Area under the curve and C-index were used to compare the predictive value of 15 NIIs in overall patients and subgroup in different menstrual statuses., Results: Nutrition status indicators prognostic nutritional index, controlling nutritional status score, glucose-to-lymphocyte ratio among 15 NIIs were found to be significantly associated with prognosis of breast cancer, and remained stable in patients in different menstrual statuses. The C-index of inflammation indicators lymphocyte-to-C-reactive protein ratio, lymphocyte-C-reactive protein ratio score, and C-reaction protein (CRP) increased with age, but the predictive value of 3 inflammation indicators did not exceed the value of nutritional indicators throughout the whole life of patients with breast cancer., Conclusions: Prognostic nutritional index, controlling nutritional status score, glucose-to-lymphocyte ratio had better predictive value for the survival of patients with breast cancer. Nutritional indicators surpassed inflammation indicators in prognostic ability for patients in different menstrual statuses. These results provide an important insight for the care of patients with breast cancer., (Copyright © 2023 Elsevier Inc. All rights reserved.)