Synthesis of three cisplatin-conjugated asymmetric porphyrin photosensitizers for photodynamic therapy.

Photodynamic therapy provides a promising solution for treating various cancer types. In this study, three distinct asymmetric porphyrin-cisplatin complex photosensitizers (ZnPt-P1, ZnPt-P2, and ZnPt-P3) were synthesized, each having unique side chains. Through a set of experiments involving singlet oxygen detection and density functional theory, ZnPt-P1 was demonstrated to have excellent efficacy, exceeding that of ZnPt-P2 and ZnPt-P3. Notably, ZnPt-1 showed significant phototoxicity while maintaining low dark toxicity when tested on HepG2 cells. Additionally, further examination revealed that ZnPt-P1 had the capability to generate reactive oxygen species within cancer cells when exposed to light irradiation. Taken together, these results highlight the potential of ZnPt-P1 as a photosensitizer for use in photodynamic therapy. This study contributes to enhancing cancer treatment methodologies and provides insights for the future development of innovative drugs for photosensitization.

Kae1 of Saccharomyces cerevisiae KEOPS complex possesses ADP/GDP nucleotidase activity.

The KEOPS complex is an evolutionarily conserved protein complex in all three domains of life (Bacteria, Archaea, and Eukarya). In budding yeast Saccharomyces cerevisiae, the KEOPS complex (ScKEOPS) consists of five subunits, which are Kae1, Bud32, Cgi121, Pcc1, and Gon7. The KEOPS complex is an ATPase and is required for tRNA N6-threonylcarbamoyladenosine modification, telomere length maintenance, and efficient DNA repair. Here, recombinant ScKEOPS full complex and Kae1-Pcc1-Gon7 and Bud32-Cgi121 subcomplexes were purified and their biochemical activities were examined. KEOPS was observed to have ATPase and GTPase activities, which are predominantly attributed to the Bud32 subunit, as catalytically dead Bud32, but not catalytically dead Kae1, largely eliminated the ATPase/GTPase activity of KEOPS. In addition, KEOPS could hydrolyze ADP to adenosine or GDP to guanosine, and produce PPi, indicating that KEOPS is an ADP/GDP nucleotidase. Further mutagenesis characterization of Bud32 and Kae1 subunits revealed that Kae1, but not Bud32, is responsible for the ADP/GDP nucleotidase activity. In addition, the Kae1V309D mutant exhibited decreased ADP/GDP nucleotidase activity in vitro and shortened telomeres in vivo, but showed only a limited defect in t6A modification, suggesting that the ADP/GDP nucleotidase activity of KEOPS contributes to telomere length regulation.

Upregulation of XRN2 acts as an oncogene in oral squamous cell carcinoma and correlates with poor prognosis.

BACKGROUD: The 5'-3' exoribonuclease 2 (XRN2) has been reported involved in several tumors. However, the clinical significance and molecular mechanism of XRN2 in oral squamous cell carcinoma (OSCC) have not been elucidated. MATERIALS AND METHODS: Immunohistochemistry (IHC) was used to investigate the expression of XRN2 in OSCC and adjacent noncancerous tissues, which was further identified by western blot and GEPIA2 database analysis. Moreover, the relationship between XRN2 expression and the clinicopathological characteristics and prognosis of OSCC patients was evaluated. In addition, in vitro, the effects of XRN2 on OSCC cells were evaluated by Cell Counting Kit-8 (CCK8) assay, colony formation assay, apoptosis assay, wound healing assay, and transwell assays. RESULTS: XRN2 was overexpressed in 44 of 77 (57.1 %) OSCC tissues. High expression of XRN2 was significantly associated with tumor differentiation (P=0.003), pathological clinical stage (P=0.045), lymph node metastasis (P=0.041), and poor overall survival (P=0.0013). Furthermore, the multivariate analysis suggested that XRN2 expression(P=0.002) was determined as an independent prognostic factor for patients with OSCC. Additionally, with functional assays in vitro, we found that downregulation of XRN2 inhibited cell proliferation, migration, and invasion, while promoted apoptosis of OSCC cells. Furthermore, knockdown of XRN2 in OSCC cells could increase the expression of E-cadherin but reduce the expression of Vimentin, which changes the characteristic of epithelial-mesenchymal transition (EMT). CONCLUSION: XRN2 is significantly overexpressed in OSCC tissues and its upregulation was closely associated with poor prognosis of OSCC patients. XRN2 could be a useful prognostic biomarker and a potential therapeutic target for OSCC.

Swc4 positively regulates telomere length independently of its roles in NuA4 and SWR1 complexes.

Telomeres at the ends of eukaryotic chromosomes are essential for genome integrality and stability. In order to identify genes that sustain telomere maintenance independently of telomerase recruitment, we have exploited the phenotype of over-long telomeres in the cells that express Cdc13-Est2 fusion protein, and examined 195 strains, in which individual non-essential gene deletion causes telomere shortening. We have identified 24 genes whose deletion results in dramatic failure of Cdc13-Est2 function, including those encoding components of telomerase, Yku, KEOPS and NMD complexes, as well as quite a few whose functions are not obvious in telomerase activity regulation. We have characterized Swc4, a shared subunit of histone acetyltransferase NuA4 and chromatin remodeling SWR1 (SWR1-C) complexes, in telomere length regulation. Deletion of SWC4, but not other non-essential subunits of either NuA4 or SWR1-C, causes significant telomere shortening. Consistently, simultaneous disassembly of NuA4 and SWR1-C does not affect telomere length. Interestingly, inactivation of Swc4 in telomerase null cells accelerates both telomere shortening and senescence rates. Swc4 associates with telomeric DNA in vivo, suggesting a direct role of Swc4 at telomeres. Taken together, our work reveals a distinct role of Swc4 in telomere length regulation, separable from its canonical roles in both NuA4 and SWR1-C.

Are Routine Postoperative Laboratory Tests Necessary After Primary Total Hip Arthroplasty?

BACKGROUND: Recently, the practice of ordering routine postoperative laboratory tests in primary total hip arthroplasty (THA) has been challenged. This study aimed to evaluate the utility of routine postoperative laboratory tests after primary elective THA in an Asian population and identify the risk factors associated with abnormal postoperative laboratory test-related intervention. METHODS: We retrospectively reviewed 395 consecutive patients who underwent primary elective THA at a single tertiary academic center. Patient clinical information and laboratory test results were collected for analysis. RESULTS: A total of 349 (88.4%) patients had abnormal postoperative laboratory test results; most patients had anemia and hypoalbuminemia. Twenty-seven (6.8%) patients received clinical intervention. Of the 307 (77.7%) patients with postoperative anemia, 7 patients received blood transfusion. Factors associated with transfusion were female gender, low body mass index, long operation time, and low preoperative hemoglobin levels. Of the 149 (37.7%) patients with postoperative hypoalbuminemia, 16 received albumin supplementation. Factors associated with albumin supplementation were female gender, long operation time, and low preoperative albumin levels. Although 36 patients had abnormal postoperative creatinine, only 1 patient required specialist consultation. For electrolyte abnormalities, hyponatremia was noted; however, no patient received sodium supplementation. Moreover, 14 patients developed hypokalemia, of which 6 required potassium supplementation; 163 patients had hypocalcemia, of which 2 received calcium supplementation. CONCLUSION: Routine laboratory tests after primary elective THA are unnecessary for most of the patients in modern clinical practice. However, for those with identified risk factors, postoperative laboratory tests still should be performed.

Never too old for hip arthroplasty: a 111-year-old woman walks out of hospital-a case report and literature review.

Centenarians population is proliferating, and hip fractures are responsible for more than 10% of all hospital admissions for centenarian patients, which represents a considerable challenge to patients and healthcare providers. Herein, we first report a case of a 111-year-old woman who suffered from a hip fracture and was successfully managed with cemented hemiarthroplasty surgery. In addition, we further reviewed case reports, news, and related studies to address the central points in managing hip fractures in the centenarian population.

The necessity of routine postoperative laboratory tests in enhanced recovery after surgery for primary hip and knee arthroplasty: A retrospective cohort study protocol.

INTRODUCTION: Over the last few decades, the concepts of minimally invasive surgery and enhanced recovery after surgery (ERAS) protocols have been introduced into the field of total joint arthroplasty (TJA), and tranexamic acid (TXA) has been widely used in TJA. Modern-day surgical techniques and perioperative care pathways of TJA have experienced unexpected improvements. Recently, the necessity of the practice of ordering routine postoperative laboratory tests for patients undergoing primary TJA has been challenged, especially in the context of implementation of ERAS protocols in TJA. These studies have consistently suggested that routine postoperative laboratory tests are not necessary in modern-day primary, unilateral total hip arthroplasty (THA) or total knee arthroplasty (TKA), and laboratory tests after surgery should only be obtained for patients with risk factors. However, it remains unclear whether routine postoperative laboratory tests after THA and TKA remains justified in the Chinese patient population. Therefore, we developed this study to address this issue. METHODS AND ANALYSIS: This retrospective cohort study will include adult patients who underwent primary unilateral THA or TKA and received multimodal perioperative care pathways according to ERAS protocols. The following patient data will be collected from the electronic medical record system: patients' demographics, preoperative and postoperative laboratory values, operation time, intraoperative blood loss, TXA use, tourniquet use, postoperative length of stay, and any medical intervention directly related to abnormal laboratory values. The main study outcomes are the incidence of acute anemia requiring transfusion and incidence of hypoalbuminemia requiring albumin supplementation. The secondary outcomes are the rates of acute kidney injury, incidence of abnormal serum sodium level, incidence of abnormal serum potassium level, and incidence of abnormal serum calcium level. These clinical data will be analyzed to determine the incidence of abnormal postoperative laboratory values following primary unilateral THA and TKA; to clarify the frequency of any medical intervention directly related to abnormal postoperative laboratory values; and to identify risk factors that predispose patients to have abnormal postoperative laboratory results. STUDY REGISTRATION: Chinese Clinical Trial Registry (http://www.chictr.org.cn): ChiCTR1900020690.

Yeast KEOPS complex regulates telomere length independently of its t6A modification function.

In Saccharomyces cerevisiae, the highly conserved Sua5 and KEOPS complex (including five subunits Kae1, Bud32, Cgi121, Pcc1 and Gon7) catalyze a universal tRNA modification, namely N6-threonylcarbamoyladenosine (t6A), and regulate telomere replication and recombination. However, whether telomere regulation function of Sua5 and KEOPS complex depends on the t6A modification activity remains unclear. Here we show that Sua5 and KEOPS regulate telomere length in the same genetic pathway. Interestingly, the telomere length regulation by KEOPS is independent of its t6A biosynthesis activity. Cytoplasmic overexpression of Qri7, a functional counterpart of KEOPS in mitochondria, restores cytosolic tRNA t6A modification and cell growth, but is not sufficient to rescue telomere length in the KEOPS mutant kae1Δ cells, indicating that a t6A modification-independent function is responsible for the telomere regulation. The results of our in vitro biochemical and in vivo genetic assays suggest that telomerase RNA TLC1 might not be modified by Sua5 and KEOPS. Moreover, deletion of KEOPS subunits results in a dramatic reduction of telomeric G-overhang, suggesting that KEOPS regulates telomere length by promoting G-overhang generation. These findings support a model in which KEOPS regulates telomere replication independently of its function on tRNA modification.

A new one-dimensional cadmium(II) coordination polymer incorporating 4-[4-(1H-imidazol-1-yl)phenyl]pyridine and 5-hydroxybenzene-1,3-dicarboxylate ligands.

The design and synthesis of new organic lgands is important to the rapid development of coordination polymers (CPs). However, CPs based on asymmetric ligands are still rare, mainly because such ligands are usually expensive and more difficult to synthesize. The new asymmetric ligand 4-[4-(1H-imidazol-1-yl)phenyl]pyridine (IPP) has been used to construct the title one-dimensional coordination polymer, catena-poly[[[aqua{4-[4-(1H-imidazol-1-yl-κN(3))phenyl]pyridine}cadmium(II)]-µ-5-hydroxybenzene-1,3-dicarboxylato-κ(3)O(1),O(1'):O(3)] monohydrate], {[Cd(C8H4O5)(C14H11N3)2(H2O)]·H2O}n, under hydrothermal reaction of IPP with Cd(II) in the presence of 5-hydroxyisophthalic acid (5-OH-H2bdc). The Cd(II) cation is coordinated by two N atoms from two distinct IPP ligands, three carboxylate O atoms from two different 5-OH-bdc(2-) dianionic ligands and one water O atom in a distorted octahedral geometry. The cationic [Cd(IPP)2](2+) nodes are linked by 5-OH-bdc(2-) ligands to generate a one-dimensional chain. These chains are extended into a two-dimensional layer structure via O-H...O and O-H...N hydrogen bonds and π-π interactions.

(3,3'-{(1E,1'E)-1,1'-[Ethane-1,2-diylbis(azan-1-yl-1-yl-idene-κN)]bis-(ethan-1-yl-1-yl-idene)}di-pyrazine 1-oxide-κN (4))bis-(nitrato-κO)nickel(II) monohydrate.

In the title complex, [Ni(NO3)2(C14H16N6O2)]·H2O, the Ni(II) atom, lying on a twofold rotation axis, is coordinated by a tetra-dentate 3,3'-{(1E,1'E)-1,1'-[ethane-1,2-diylbis(azan-1-yl-1-yl-idene)]bis-(ethan-1-yl-1-yl-idene)}di-pyrazine 1-oxide ligand and two mutually trans monodentate nitrate anions in a distorted o-cta-hedral geometry. The lattice water mol-ecule is located on a twofold rotation axis. The complex mol-ecules are linked by the water mol-ecules through O-H⋯O hydrogen bonds into a chain along [001]. Further C-H⋯O hydrogen bonds lead to the formation of a three-dimensional network.

Aqua-[1-(pyrazin-2-yl)ethanone oximato-κ²N,N'][1-(pyrazin-2-yl)ethanone oxime-κ²N,N'](thio-cyanato-κN)nickel(II).

In the title complex, [Ni(C6H6N3O)(NCS)(C6H7N3O)(H2O)] or [Ni(mpko)(SCN)(mpkoH)(H2O)] [where mpkoH = 1-(pyrazin-2-yl)ethanone oxime], the Ni(II) cation is in a slightly distorted octa-hedral geometry, being coordinated in the equatorial plane by four N atoms from two different mpkoH ligands, one of which is deprotonated, and by one N atom from a thio-cyanate anion and one O atom from a water mol-ecule in the axial positions. There is an intra-molecular O-H⋯O hydrogen bond involving the oxime units of the two ligands. In the crystal, a three-dimensional supra-molecular architecture is formed by O-H⋯O and O-H⋯N hydrogen bonds.