Search

Middle Pleistocene rhinocerotid material from the upper strata of Jinyuan Cave, Luotuo Hill, Dalian, is described in the present study. The specimens mainly consist of maxillary and mandible with dentition of juvenile and aged individuals, respectively. Based on comparison between the new discovery and known records of Pleistocene rhinocerotid, the Jinyuan Cave specimens are most similar to Stephanorhinus kirchbergensis and then have been identified as Stephanorhinus cf. kirchbergensis. Tooth loss has been present on the Jinyuan Cave rhinocerotid specimen, represented by a mandible without both p2s. This problem could be a result of heredity issues. This condition may be due to mechanical damage from a coarse diet, which can lead to tooth loss and alveolar remodelling, according to the findings from an environmental investigation. [ABSTRACT FROM AUTHOR]

Early Pleistocene Equus specimens collected from Jinyuan Cave, Luotuo Hill, Dalian, have been described. The newly reported specimens include two forms. The large-sized form is identified as E. sanmeniensis. The small-sized form is identified as E. teilhardi. E. sanmeniensis shares highly similar features with another huge-sized species E. wangi. Based on further comparison of the new and classic specimens of E. sanmeniensis, the differences between these two species are more obvious. For now, Early Pleistocene Equus in Jinyuan Cave includes E. sanmeniensis, E. teilhardi and E. qingyangensis, same as the composition of Nihewan fauna (s.s.) in Hebei and similar to Bajiazui fauna in Gansu. Among Early Pleistocene Equus in China, medium-sized forms are wide distributed, while distributions of large-sized form are relatively limited, and this is likely relative to difference of adaptability. From Early to Late Pleistocene, Equus community seemed to keep in a pattern of one large-sized species accompanied with two medium-sized species with slender and robust limbs, respectively. This pattern had occurred since around 2.1 Ma, likely established during the second immigration event of Equus from North America to Eurasia. [ABSTRACT FROM AUTHOR]

Xenocyon lycaonoides is a well-represented large canid known from the middle Early Pleistocene to Middle Pleistocene in Europe, central Asia, and Alaska, yet its fossil record in eastern Asia is extremely poor. Here we report a well-preserved palatal part of the skull of this species from Jinyuan Cave of Luotuo Hill, Puwan, Dalian of Liaoning Province, northeastern China. The new material confirms the presence of this species in eastern Asia during the early Middle Pleistocene, supporting a Holarctic distribution of this lineage during the Mid-Pleistocene climate change. The morphology of the new material suggests that the Middle Pleistocene X. lycaonoides is more derived than the late Early Pleistocene population, and is distinct from the living Lycaon pictus, and imply the different evolutionary direction from Lycaon. Our analyses support a generic distinction of the Xenocyon from Lycaon. X. lycaonoides can not be the direct ancestor of Lycaon, but is a related taxon that lived in Eurasia and North America. The lineage includes Xenocyon, and Lycaon Brookes, 1827, and partially contributes to Cynotherium Studiati, 1857, showing two independent Island specialisation events, making it one of the most successful lineages of canids ever known. [ABSTRACT FROM AUTHOR]

Background: Leukocyte Ig-like receptor B family 4 (LILRB4) as an immune checkpoint on myeloid cells is a potential target for tumor therapy. Extensive osteolytic bone lesion is the most characteristic feature of multiple myeloma. It is unclear whether ectopic LILRB4 on multiple myeloma regulates bone lesion., Methods: The conditioned medium (CM) from LILRB4-WT and -KO cells was used to analyze the effects of LILRB4 on osteoclasts and osteoblasts. Xenograft, syngeneic and patient derived xenograft models were constructed, and micro-CT, H&E staining were used to observe the bone lesion. RNA-seq, cytokine array, qPCR, the activity of luciferase, Co-IP and western blotting were used to clarify the mechanism by which LILRB4 mediated bone damage in multiple myeloma., Results: We comprehensively analyzed the expression of LILRB4 in various tumor tissue arrays, and found that LILRB4 was highly expressed in multiple myeloma samples. The patient's imaging data showed that the higher the expression level of LILRB4, the more serious the bone lesion in patients with multiple myeloma. The conditioned medium from LILRB4-WT not -KO cells could significantly promote the differentiation and maturation of osteoclasts. Xenograft, syngeneic and patient derived xenograft models furtherly confirmed that LILRB4 could mediate bone lesion of multiple myeloma. Next, cytokine array was performed to identify the differentially expressed cytokines, and RELT was identified and regulated by LILRB4. The overexpression or exogenous RELT could regenerate the bone damage in LILRB4-KO cells in vitro and in vivo. The deletion of LILRB4, anti-LILRB4 alone or in combination with bortezomib could significantly delay the progression of bone lesion of multiple myeloma., Conclusions: Our findings indicated that LILRB4 promoted the bone lesion by promoting the differentiation and mature of osteoclasts through secreting RELT, and blocking LILRB4 singling pathway could inhibit the bone lesion., (© 2024. The Author(s).)

Leukemia stem cells (LSC) require frequent adaptation to maintain their self-renewal ability in the face of longer exposure to cell-intrinsic and cell-extrinsic stresses. However, the mechanisms by which LSC maintain their leukemogenic activities, and how individual LSC respond to stress, remain poorly understood. Here, we found that DNAJC10, a member of HSP40 family, was frequently up-regulated in various types of acute myeloid leukemia (AML) and in LSC-enriched cells. Deficiency of DNAJC10 leads to a dramatic increase in the apoptosis of both human leukemia cell lines and LSC-enriched populations. Although DNAJC10 is not required for normal hematopoiesis, deficiency of Dnajc10 significantly abrogated AML development and suppressed self-renewal of LSC in the MLL-AF9-induced murine leukemia model. Mechanistically, inhibition of DNAJC10 specifically induces endoplasmic reticulum stress and promotes activation of PERK-EIF2α-ATF4 branch of unfolded protein response (UPR). Blocking PERK by GSK2606414 (PERKi) or shRNA rescued the loss of function of DNAJC10 both in vitro and in vivo. Importantly, deficiency of DNAJC10 increased sensitivity of AML cells to daunorubicin (DNR) and cytarabine (Ara-C). These data revealed that DNAJC10 functions as an oncogene in MLL-AF9-induced AML via regulation of the PERK branch of the UPR. DNAJC10 may be an ideal therapeutic target for eliminating LSC, and improving the effectiveness of DNR and Ara-C.

In recent years, nearly 20 cave sites with rich assemblages of mammalian fossils have been found and excavated in the Chongzuo area, Guangxi Zhuang Autonomous Region, China. Their ages are distributed throughout the entire Pleistocene Epoch. These discoveries have greatly facilitated our understanding of the evolution of the Stegodon-Ailuropoda fauna and the environmental context of human evolution in southern China. Here, we present a preliminary report on a diverse late Middle Pleistocene mammalian fauna from the Yixiantian Cave in southern China, which is a typical representative of the Stegodon-Ailuropoda fauna (sensu lato). The fossil mammals are represented by isolated dental remains only. In 2010 and 2011, two seasons of systematic excavations at the Yixiantian Cave yielded a total of 4,958 identifiable mammalian teeth. They were identified as belonging to 37 species and 6 orders of mammals. In addition, the tooth type of all the teeth representing each species was also determined where possible. A single fragmentary molar was identified as belonging to Gigantopithecus blacki, indicating that its population had declined sharply at this time and was on the brink of extinction. Description of the Yixiantian fauna will not only help better characterize the composition of the Stegodon-Ailuropoda fauna during the late Middle Pleistocene, but also clarify our understanding of the paleoenvironmental context at a time just prior to the extinction of G. blacki., (© 2023 American Association for Anatomy.)

Objective: Inbred strains of mice offer promising models for understanding the genetic basis of age-related hearing loss (AHL). NOD/LtJ, A/J, DBA/2J and C57BL/6J mice are classical models of age-related hearing loss and exhibit early onset of pathology of AHL. This study was carried out to characterize the early pathology of cochlear stereocilia in the four mouse strains with age-related hearing loss., Methods: The structural features of stereocilia in NOD/LtJ, A/J, DBA/2J and C57BL/6J mice were observed by scanning electron microscopy (SEM) at age 2, 4, 6 or 8, and 10 or 12 weeks. Meanwhile, auditory-evoked brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) amplitudes of the mice were measured at various intervals (3, 4, 6, 8, 10 and 12 weeks of age)., Results: The ABR thresholds in NOD/LtJ, A/J and DBA/2J mice increased with age from 3 to 12 weeks. DPOAE amplitudes in NOD/LtJ, A/J, DBA/2J mice were very low at 4 weeks and became negative at 8 weeks at f2 frequency of 17 672 Hz. In addition to the progressive hearing loss, the four mouse strains displayed early onset (at 2 weeks of age) and progressive degeneration of stereocilia in hair cells., Conclusion: Early degeneration of stereocilia contributes to the functional impairment of hair cells and hearing loss in NOD/LtJ, A/J, DBA/2J and C57BL/6J mice.

Fascin2 (FSCN2) is an actin cross-linking protein that is mainly localized in retinas and in the stereocilia of hair cells. Earlier studies showed that a deletion mutation in human FASCIN2 ( FSCN2 ) gene could cause autosomal dominant retinitis pigmentosa. Recent studies have indicated that a missense mutation in mouse Fscn2 gene (R109H) can contribute to the early onset of hearing loss in DBA/2J mice. To explore the function of the gene, Fscn2 was knocked out using TALEN (transcription activator-like effector nucleases) on the C57BL/6J background. Four mouse strains with deletions of 1, 4, 5, and 41 nucleotides in the target region of Fscn2 were developed. F1 heterozygous ( Fscn2 +/- ) mice carrying the same deletion of 41 nucleotides were mated to generate the Fscn2 -/- mice. As a result, the Fscn2 -/- mice showed progressive hearing loss, as measured in the elevation of auditory brainstem-response thresholds. The hearing impairment began at age 3 weeks at high-stimulus frequencies and became most severe at age 24 weeks. Moreover, degeneration of hair cells and loss of stereocilia were remarkable in Fscn2 -/- mice, as revealed by F-actin staining and scanning electron microscopy. Furthermore, compared to the controls, the Fscn2 -/- mice displayed significantly lower electroretinogram amplitudes and thinner retinas at 8, 16, and 24 weeks. These results demonstrate that, in C57BL/6Jmice, Fscn2 is essential for maintaining ear and eye function and that a null mutation of Fscn2 leads to progressive hearing loss and retinal degeneration., (Copyright © 2018 Liu et al.)

The vascular remodeling process plays an important role in the pathology of hypoxia-induced pulmonary hypertension, and it includes cell proliferation, cell motility, cell synthesis and collagen coagulation. Due to their proliferation and synthesis ability, the adventitial fibroblasts are thought to be critical in the vascular remodeling process initiated in response to hypoxia. However, the factors driving hypoxia-induced fibroblast proliferation and synthesis have yet to be elucidated, and the treatment regimens to treat hypoxia remain ineffective. As forthis study, its purpose was to examine the effects exerted by SB-431542, a small-molecule antagonist of transforming growth factor-β-receptor, on the proliferation, synthesis and collagen coagulation in cultured adventitial fibroblasts. Another aim of this study was to assess the inhibitory ability of SB-431542 on pulmonary vascular remodeling in chronic hypoxia in vivo.The cell morphology and proliferation of cultured adventitial fibroblasts was assessed by laser confocal microscopy and the MTT assay, respectively. Additionally, collagen synthesis was determined by hydroxyproline chromatography, while the expression of cytokines in adventitial fibroblasts and lung tissues was evaluated by immunohistochemical and reverse transcription PCR analyses. The results indicated that the exposure of cultured fibroblasts to 1% oxygen led to the up regulation of cell proliferation, cell synthesis. In addition, increased expression of cytokines and collagen was detected in vivo in the pulmonary artery adventitia of rats exposed to chronic hypoxia. Conversely, SB-431542 inhibited fibroblast proliferation and synthesis in the process of hypoxia-induced pulmonary hypertension (P < 0.01). Thus, the results suggested that by reducing cell proliferation, cell synthesis of vascular adventitia, small molecule inhibitors of the TGF-β1 receptors may offer a novel therapy for pulmonary hypertension.

We investigated the effects of pyrrolidine dithiocarbamate (PDTC) on intrapulmonary expression of nuclear factor-κB (NF-κB), and apoptosis in rats with severe acute pancreatitis (SAP). We induced SAP, then used immunohistochemistry, TUNEL staining, quantitative PCR assays and western blotting to examine PDTC effects. Treatment with PDTC resulted in interstitial edema and widening of the basement membrane, with swollen mitochondria and aggregation of nuclear chromatin. Expression of NF-κB, Fas, Bcl-2 and TNF-α in lung tissues of SAP rats was increased, with NF-κB, Fas and TNF-α levels maximal after 6 h. PDTC appeared to ameliorate pathological changes, with low levels of NF-κB, Fas, TNF-α, and Caspase-3 mRNA observed and a lower apoptosis index compared with that seen in SAP rats. Expression of NF-κB could be involved in lung tissue apoptosis during SAP. We postulate that PDTC inhibits the activation of NF-κB and apoptosis, effectively alleviating the severity of lung injury.